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[ CAS No. 463-40-1 ] {[proInfo.proName]}

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Chemical Structure| 463-40-1
Chemical Structure| 463-40-1
Structure of 463-40-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 463-40-1 ]

CAS No. :463-40-1 MDL No. :MFCD00065720
Formula : C18H30O2 Boiling Point : -
Linear Structure Formula :- InChI Key :DTOSIQBPPRVQHS-PDBXOOCHSA-N
M.W : 278.43 Pubchem ID :5280934
Synonyms :
Octadecatrienoic acid (all cis-9,12,15);alpha-Linolenic acid;DPN63401;C18:3 (all cis-9,12,15) Fatty acid

Calculated chemistry of [ 463-40-1 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.61
Num. rotatable bonds : 13
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 88.99
TPSA : 37.3 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -3.41 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.36
Log Po/w (XLOGP3) : 6.46
Log Po/w (WLOGP) : 5.66
Log Po/w (MLOGP) : 4.38
Log Po/w (SILICOS-IT) : 5.59
Consensus Log Po/w : 5.09

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 1.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -4.78
Solubility : 0.00464 mg/ml ; 0.0000167 mol/l
Class : Moderately soluble
Log S (Ali) : -7.04
Solubility : 0.0000255 mg/ml ; 0.0000000916 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -3.96
Solubility : 0.0308 mg/ml ; 0.000111 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.03

Safety of [ 463-40-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 463-40-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 463-40-1 ]

[ 463-40-1 ] Synthesis Path-Downstream   1~72

  • 2
  • [ 463-40-1 ]
  • [ 59044-29-0 ]
YieldReaction ConditionsOperation in experiment
64.35% With phosgene; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Green chemistry; Alpha-Linolenic acid (100 g, 0.36 mol),Xylene (100g) was added to the reactor, heated to reflux, the reaction of phosgene (301.96g, 3.05mol), the product content of 93.35% after the temperature dropped to room temperature, nitrogen into the residual phosgene and hydrogen chloride , The insoluble sticky material was separated. The o-xylene solution was distilled under reduced pressure. The solvent was distilled off and the solvent was evaporated under reduced pressure to obtain 69.08 g of linolenoyl chloride in a yield of 64.35% and a content of 92.08%.
With oxalyl dichloride; In dichloromethane; at 0 - 20℃; for 6h; General procedure: To a solution of carboxylic acid (1 equiv) in CH2Cl2, oxalyl chloride (3.1 equiv) was added at 0 C, and the mixture was stirred at room temperature for 6 h. The solvent was removed to yield crude acyl chloride. A solution of the acyl chloride (1 equiv), juglone (3 equiv) and DMAP (0.1 equiv) in pyridine was stirred at room temperature. After the mixture had been stirred for 3 h, the reaction was quenched by the addition of 1 M aqueous HCl solution. The resulting mixture was extracted with EtOAc. The extract was washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by silica gel chromatography using hexanes/ethyl acetate as the eluent.
With thionyl chloride; In benzene; for 4h;Reflux; General procedure: The recovery standard pentadecanoic acid cholesteryl ester(hereafter referred to as 15:0-CE) was prepared accordingto Lusby et al. [20] with slight modifications. Pentadecanoicacid (121 mg, 0.5 mmol) was placed in a 50-ml flaskand dissolved in 10 ml of toluene. About 120 mul thionylchloride was added, and the solution was refluxed for 4 hto obtain the acid chloride. Afterwards, the remaining thionylchloride and parts of the toluene were removed underreduced pressure. To the residue (about 2 ml), 153 mgcholesterol (0.4 mmol) dissolved in 10 ml toluene wasadded, and the solution was stirred overnight at room temperature.The solvent was removed on a rotary evaporator,and the residue was re-dissolved in 4 ml n-hexane. Thissolution was purified by SPE. For this purpose, 15 g ofsilica gel deactivated with 20 % water (w/w) was giveninto a glass column (i.d. 2.5 cm) and pre-conditionedwith n-hexane. After 50 ml of n-hexane (fraction 1), three50-ml fractions (fractions 2-4) were collected with n-hexane/ethyl acetate (99:1, v/v) as eluent. Fractions 3 and 4yielded 154.3 and 64.8 mg of 15:0-CE. The purity inboth fractions was >99 % according to GC/MS and NMRspectroscopy analysis.
With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; at 0℃;Inert atmosphere; General procedure: For compounds2-4, the corresponding acid chlorides (oleic, linoleic, andlinolenic acid) were prepared by treatment of the acid (1 equiv)in anhydrous dichloromethane and thionyl chloride (1.1 equiv)under nitrogen at 0 C with a catalytic amount of DMF. Acidchloride was distilled under vacuum and used immediately forthe next step. Curcumin (1 equiv) was dissolved in anhydrouspyridine at 0 C under nitrogen and treated with different acidchlorides. The reaction mixture was allowed to stir for 2 h atroom temperature and then heated at 60 C for an additional 2h. After the mixture had been cooled to room temperature,excess pyridine was evaporated under high vacuum. Theresulting residue was subjected to column chromatography.Compounds 5 and 6 were synthesized as describedpreviously.34 The chemical structure of 1-6 is shown in Figure1.
With oxalyl dichloride; In dichloromethane; at 20℃;Inert atmosphere; alpha-linolenic acid (200 mg, 0.72 mmol) was dissolved in dichloromethane (6.0 mL), after adding oxalyl chloride (200 muL, 2.33 mmol) and stirred at room temperature under a nitrogen atmosphere. Tracking of the reaction, the reaction mixture pyridine: methanol = 1: a small amount quenched with 1 solution, the methyl ester of alpha- linolenic acid was followed by confirming on TLC. After four hours, to obtain an oily residue and the solvent was distilled off under reduced pressure. Purification of the residue is not performed, it was used in the next reaction.
With oxalyl dichloride; N,N-dimethyl-formamide; In chloroform; at 20℃; for 4h;Inert atmosphere; Reflux; To a solution of linolenic acid (278 mg, 1.00 mmol) and DMF (50 muL, 0.65 mmol) in dry CHCl3 (5 mL), under an argon atmosphere, a solution of oxalyl chloride (94 muL, 1.09 mmol) in dry CHCl3 (1 mL) was added dropwise. After 1 h the mixture was heated at reflux for a further 3 h. The resulting acid chloride was cooled to r.t. and put aside for use in the next part of the reaction.
With oxalyl dichloride; In benzene; at 20℃; for 6h;Inert atmosphere; General procedure: A solution of the appropriate FA (0.002 mol) in anhydrousC6H6 (15 mL) was stirred, treated with oxalyl chloride (0.19 mL, 0.0022 mol), held at room temperature under Ar for 6 h, and evaporated in a rotary evaporator. The product was again dissolved in C6H6 and evaporated to remove traces of oxalylchloride and dissolved in anhydrous CH2Cl2 (15 mL) for subsequent acylation of N-deacetyllappaconitine (1).
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h;Inert atmosphere; Schlenk technique; General procedure: To a stirred solution of the fatty acid (1 eq., 0.78 mmol) and a dropof DMF in dry dichloromethane (5 ml) was added dropwise oxalylchloride (3 eq., 297 mg, 2.34 mmol) at 0 C. The reaction mixture waswarmed slowly up to rt and stirred for further 3 h. Solvent and excessoxalyl chloride were removed in vacuo and the resulting acid chloridewas used next step without purification.
With oxalyl dichloride; In dichloromethane; at 20℃; for 2.16667h;Cooling with ice; Linolenic acid (1 g, 3.5 mmol), was dissolved in 10 mL DCM and cooled down in an ice bath. Oxalyl chloride (0.9 g, 7 mmol) was added dropwise to the reaction mixture. The reaction mixture was stirred for further 10 min in an ice bath and returned to room temperature and stirred for additional 2h. The excess oxalyl chloride was removed and the residue was redissolved in DCM and evaporated to dryness to remove the oxalyl chloride and obtain an oily residue of linolenoyl chloride.

  • 3
  • [ 463-40-1 ]
  • [ 627-98-5 ]
  • 5-methylhexyl linolenate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid at 150℃; for 3h;
  • 5
  • [ 463-40-1 ]
  • [ 87984-82-5 ]
YieldReaction ConditionsOperation in experiment
With Myxococcus xanthus lipoxygenase; In aq. buffer; at 30℃; for 0.05h;pH 8.5;Enzymatic reaction; General procedure: The specific activity of M. xanthus LOX for PUFA substrates was determined by measuring the increase in absorbance at 234nm using a Beckman Coulter DU-700 spectrophotometer (Brea, CA, USA) after incubation at 30C in 50mM EPPS (pH8.5) buffer containing 0.1mM substrate and 0.6-3.6mugmL-1 enzyme for 3min. Only the part of each reaction showing a linear correlation between product concentration and time and the extinction coefficient of 25,000M-1cm-1 for conjugated fatty acids was used to calculate enzyme activity. One unit of LOX activity was defined as the amount of enzyme required to produce 1mumol per min HpFAs at 30C and pH8.5. Specific activity, which was determined with 1mL reaction volume, was defined as the amount of product per amount of protein per unit reaction time. To determine kinetic parameters, the reactions were performed at 30C in 50mM EPPS (pH8.5) buffer by varying the amounts of PUFAs from 10 to 900muM for 1min, and enzyme activity was determined by the polarographic assay using a Clark-type electrode (YSI 5300A, Yellow Springs, OH, USA). Kinetic parameters, Km (mM) and kcat (min-1), were calculated using the enzyme concentration and Hanes-Woolf plot derived from the Michaelis-Menten equation. To calculate the catalytic constant kcat, the amount of protein was divided by total molecular mass.
  • 6
  • (2S)-3-O-[α-D-galactopyranosyl-(1->6)-β-D-galactopyranosyl]-1-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-sn-glycerol [ No CAS ]
  • [ 463-40-1 ]
  • [ 301-00-8 ]
  • [ 33600-42-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate Yield given. Yields of byproduct given;
  • 7
  • [ 463-40-1 ]
  • [ 18637-83-7 ]
  • [ 64833-93-8 ]
YieldReaction ConditionsOperation in experiment
In chloroform at 45℃; for 1h;
With N-ethyl-N,N-diisopropylamine In chloroform at 0℃; for 1h;
  • 8
  • [ 171520-42-6 ]
  • [ 463-40-1 ]
  • [ 301-00-8 ]
  • [ 16232-91-0 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In methanol for 25h; Heating; Yield given. Yields of byproduct given;
  • 9
  • [ 301-00-8 ]
  • [ 463-40-1 ]
YieldReaction ConditionsOperation in experiment
93% With lithium hydroxide In tetrahydrofuran; water for 18h; Ambient temperature;
With water; sodium hydroxide In methanol for 1h; Heating;
  • 10
  • [ 27538-10-9 ]
  • [ 463-40-1 ]
  • 2-ethyl-4-linoleonyloxy-5-methyl-3(2H)-furanone [ No CAS ]
  • 5-ethyl-4-linoleonyloxy-2-methyl-3(2H)-furanone [ No CAS ]
  • 11
  • [ 67-56-1 ]
  • [ 463-40-1 ]
  • [ 301-00-8 ]
YieldReaction ConditionsOperation in experiment
95% With sulfuric acid for 2h; Heating;
With hydrogenchloride
61 - 99 %Chromat. at 270 - 400℃; for 0.0333333 - 0.333333h; 3.13; 3.14; 3.15; 3.5; 5.1 (Esterification Reaction of Fatty Acid) An esterification reaction of a fatty acid and methanol was conducted using, as a raw material, palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid (all manufactured by Nacalai Tesque) commercially available as a reagent, and under conditions of volume ratio, temperature, pressure and reaction time shown in Table 5. For the esterification reaction of a fatty acid and methanol, a fatty acid and methanol were filled at a mole ratio of 1:42 in a Inconel-625 reaction tube having a content volume of 5 ml, and the same procedure as in the methyl-esterification reaction in Example 1 was conducted. After removal of unreacted methanol and produced water in the same manner as in Example 1, the reaction product was dissolved in fresh methanol and HPLC analysis was conducted. From the HPLC analysis result, the conversion from a fatty acid into a fatty acid alkyl ester (=yield of methyl ester) was obtained. The results are shown in Table 5 together with reaction conditions. TABLE 5 Reac- Tem- tion Fatty Fatty acid (ml)/ perature Pressure time Yield Example acid methanol (ml) (° C.) (Mpa) (min) (%) Example 3-1C16-0 0.91:4.09 270 17 20 90 Example 3-2C16-0 0.91:4.09 300 24 7 88 Example 3-3C16-0 0.91:4.09 350 43 4 75 ComparativeC16-0 0.91:4.09 400 75 2 92 example 3-1 Example 3-4C18-0 0.91:4.09 270 17 20 98 Example 3-5C18-0 0.91:4.09 300 24 7 98 Example 3-6C18-0 0.91:4.09 350 43 4 100 ComparativeC18-0 0.91:4.09 400 75 2 100 example 3-2 Example 3-7C18-1 0.91:4.09 270 17 20 98 Example 3-8C18-1 0.91:4.09 300 24 7 98 Example 3-9C18-1 0.91:4.09 350 43 4 98 ComparativeC18-1 0.91:4.09 400 75 2 94 example 3-3 Example 3-10C18-2 0.91:4.09 270 17 20 98 Example 3-11C18-2 0.91:4.09 300 24 7 98 Example 3-12C18-2 0.91:4.09 350 43 4 87 ComparativeC18-2 0.91:4.09 400 75 2 80 example 3-4 Example 3-13C18-3 0.91:4.09 270 17 20 99 Example 3-14C18-3 0.91:4.09 300 24 7 96 Example 3-15C18-3 0.91:4.09 350 43 4 93 ComparativeC18-3 0.91:4.09 400 75 2 61 example 3-5 C16-0: palmitic acid, C18-0: stearic acid, C18-1: oleic acid, C18-2: linoleic acid, C18-3: linolenic acid An esterification reaction of a fatty acid and alcohol or a transesterification of rapeseed oil and alcohol was conducted using, as a raw material, fats and oils and alcohols shown in Table 7, under conditions of mole ratio, temperature, pressure and reaction time shown in Table 7. Since about 98.5% of rapeseed oil is composed of a tri-glyceride, the reaction from rapeseed oil can be judged to be a transesterification. The reaction product was subjected to HPLC analysis in the same manner as in Example 1, from the HPLC analysis result, conversion into a fatty acid alkyl ester from a fatty acid or rapeseed oil (=yield of alkyl ester) was obtained. The results are shown in Table 7 together with the reaction conditions. TABLE 7 Alcohol/fats and oils Temperature Pressure Reaction Example (mole ratio) Fats and oils Alcohol (° C.) (Mpa) time (min) Yield (%) Example 42/1C18-3 Methanol 300 20 8 96.2 5-1 Example 42/1C18-2 300 20 8 95.1 5-2 Example 42/1C18-1 300 20 8 95.8 5-3 Example 42/1C18-0 300 20 8 94.7 5-4 Example 42/1C16-0 300 20 8 94.0 5-5 Example 42/1 Rapeseed 300 20 15 98.0 5-6 oil Example 42/1 Rapeseed 350 43 4 98.0 5-7 oil Example 42/1C18-3 Ethanol 300 15 12 94.6 5-8 Example 42/1C18-2 300 15 14 97.4 5-9 Example 42/1C18-1 300 15 14 95.9 5-10 Example 42/1C18-0 300 15 15 91.2 5-11 Example 42/1C16-0 300 15 14 91.7 5-12 Example 42/1 Rapeseed 300 15 45 96.7 5-13 oil Example 42/1 Rapeseed 350 25 10 97.1 5-14 oil Example 42/1C18-3 1-propanol 300 10 15 97.0 5-15 Example 42/1C18-2 300 10 14 92.7 5-16 Example 42/1C18-1 300 10 14 92.3 5-17 Example 42/1C18-0 300 10 14 89.6 5-18 Example 42/1C16-0 300 10 14 90.1 5-19 Example 42/1 Rapeseed 300 10 45 96.1 5-20 oil Example 42/1 Rapeseed 350 23 14 98.8 5-21 oil Example 42/1C18-3 1-butonal 300 9 15 97.3 5-22 Example 42/1C18-2 300 9 14 92.4 5-23 Example 42/1C18-1 300 9 14 86.1 5-24 Example 42/1C18-0 300 9 14 82.5 5-25 Example 42/1C16-0 300 9 14 81.1 5-26 Example 42/1 Rapeseed 300 9 45 87.1 5-27 oil Example 42/1 Rapeseed 350 23 14 95.3 5-28 oil Example 42/1 Rapeseed 1-octanol 300 6 45 68.7 5-29 oil Example 42/1 Rapeseed 350 19 20 90.7 5-30 oil C16-0: palmitic acid, C18-0: stearic acid, C18-1: oleic acid, C18-2: linoleic acid, C18-3: linolenic acid
With hydrogenchloride In chloroform at 90℃; for 1h;
With toluene-4-sulfonic acid for 3h; Reflux;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;
With sulfuric acid In chloroform at 94℃; for 0.5h;
With sulfuric acid at 80℃; for 1.5h; Preparation of Fatty Acid Methyl Esters General procedure: A solution of methanolic sodium hydroxide (9:1, 5 mL) was added to an oil sample(30 mg) and the mixture was heated under reflux for 90 min. After cooling, deionized water(10 mL) was added and the mixture was shaken for a few seconds. Unsaponified fatty acidswere discarded by extraction with hexane (3 5 mL). The layer below was collected andadjusted to pH 3 (by 6 N HCl), followed by extraction with hexane (3 5 mL). The organiclayer was removed under reduced pressure. The obtained fatty acid was further mixedwith a solution of 2% H2SO4 in methanol, and the mixture was heated under reflux at 80 Cfor 90 min. After cooling to ambient temperature, water (0.5 mL) was added, followed byextraction with hexane (3 5 mL). The methyl ester was evaporated to dryness, weighedand solubilized in hexane (1 mL) before injection into the gas chromatograph.

  • 12
  • [ 463-40-1 ]
  • [ 3897-89-0 ]
  • 4-[(cis,cis,cis-9,12,15-octadecatrienoyloxy)methy]catechol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With lipase from Pseudomonas Cepacia In tetrahydrofuran; di-isopropyl ether at 60℃; for 240h;
With lipase from Pseudomonas Cepacia In tetrahydrofuran; di-isopropyl ether Heating;
  • 13
  • [ 463-40-1 ]
  • [ 67597-26-6 ]
YieldReaction ConditionsOperation in experiment
With 13-lipoxygenase from soybean; In ethanol; at 4℃; for 0.75h;pH 10.4; Following the procedure described in Literature21 12-OPDA wasprepared from LeA (70%: 62170) using crude soybean lipoxygenase(Glycine max L.) type 1-S (Sigma, L7395) or cell lysate of LOX 6-expressing E. coli. All steps were performed aerobically unless statedotherwise. 120 mL of a 1:1 mixture of LeA and 95% ethanol wasincubated with 4 mg soybean LOX (SLOX) dissolved in 10 mL100 mM borate buffer (pH 10.4). Following the 45 min incubationat 4 C with stirring (400-700 rpm) 1 mL AOS lysate and 2 mLAOC lysate were added. After 15 min of incubation on ice a secondaddition of 1 mL AOS lysate, 2 mL AOC lysate and, additionally,30 mL glacial acetic acid was made and the incubation continuedfor 15 min. The lipids were extracted according to Bligh and Dyer.23Briefly, the reaction mixture was extracted with 200 mL glacialacetic acid, 16 mL methanol and 16 mL chloroform. After phaseseparation the upper phase was re-extracted with 16 mL chloroform.The combined lower chloroform phases were recovered,the solvent was evaporated under nitrogen and the remaining productwas dissolved in 400 ml methanol, filtered (mesh size 0.45 mm)and purified via RP-HPLC. Using LOX6 extract, the lysate (see 4.2)with the total protein content of approximately 5 mg/ml was incubatedat 25 C with 120 mL of a 1:1 mixture of LeA and 95% ethanolfor 2 min followed by a 3 min incubation step with 2 ml 100 mMborate buffer (pH 10.4). Following 35 min incubation at 4 C withstirring (400-700 rpm) 1 mL AOS lysate and 2 mL AOC lysate wereadded. After incubation on ice for 35 min with stirring (400-700 rpm), 2 mL of AOC was added followed by addition of 1 mLAOS. The production reaction was performed as described above.1H NMR (500 MHz, CDCl3) d/ppm = 7.73 (dd, J = 6.0, 2.7 Hz, 1H,H2), 7.60 (d, J = 5.7 Hz, 1H, H2(trans_12-OPDA)), 6.18 (dd, J = 5.9, 1.7Hz, 1H, H3), 6.12 (d, J = 5.9 Hz, 1H, H3(trans_12-OPDA)), 5.46-5.32(m, 2H, H18,19), 2.97 (ddt, J = 10.8, 7.6, 3.6 Hz, 1H, H1), 2.50 (dt,J = 15.3, 5.4 Hz, 1H, H17b), 2.47-2.41 (m, 1H, H5), 2.35 (t, J = 7.5Hz, 2H, H7), 2.17-2.10 (m, 1H, H17a), 2.06 (d, J = 7.5 Hz, 2H, H20),1.72 (td, J = 11.1, 5.0 Hz, 1H, 13a), 1.63 (p, J = 7.2 Hz, 3H, H8), 1.32(q, J = 7.1, 5.9 Hz, 8H, H9,10,11,12), 1.15 (dtd, J = 14.3, 9.6, 4.5 Hz,1H, H13b), 0.97 (t, J = 7.5 Hz, 3H, H21). 13C NMR (500 MHz, CDCl3)d/ppm = 211.05 (C4), 171.35 (C6), 167.28 (C2), 133.13 (C3), 132.59(C19), 127.10 (C18), 50.00 (C4), 44.43 (C1), 34.02 (C7), 30.90 (C13),29.70 (C11), 29.24 (C10), 29.09 (C9), 27.72 (C12), 24.75 (C8), 23.93(C17), 20.94 (C20), 14.15 (C21). The 1H NMR and 13C NMR were identicalto those reported.35
  • 14
  • [ 463-40-1 ]
  • [ 152698-45-8 ]
  • [ 651306-17-1 ]
YieldReaction ConditionsOperation in experiment
91% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃;Inert atmosphere; General procedure: compound 5 ( 0.19 g, 0.0005 mol) was dissolved in anhydrous dichloromethane (5 mL); linolenic acid (0.29 g, 0.0010 mol), dicyclohexylcarbodiimide (0.204 g, 0.0010 mol) and DMAP (0.012 g, 0.00010mol) were added under argon; the reaction mixture was stirred overnight at room temperature; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 6 (0.406 g, 0.00043 mol, 94%).
  • 15
  • [ 463-40-1 ]
  • [ 506-44-5 ]
YieldReaction ConditionsOperation in experiment
100% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; Example 6 ALA Alcohol, 6 An oven-dried 100 mL round bottomed flask was charged with lithium aluminum hydride (2.04 g, 53.87 mmol) in anhydrous THF (20 mL). The mixture was cooled to 0 C. with an ice-water bath. To this suspension was added drop-wise a solution of ALA (5.00 g, 17.96 mmol) in THF (20 mL) via syringe under argon. When the addition was complete, the mixture was allowed to warm to RT and stirred for 4 hr. The reaction mixture was then quenched at 0 C. by slow drop-wise addition of a saturated aqueous solution of sodium sulfate (10 mL). The mixture was then allowed to stir for 0.5 hr at RT and then filtered through a Buechner funnel. The residue was rinsed with THF. The filtrate and washings were combined and concentrated under reduced pressure to obtain 4.75 g of ALA alcohol as colorless oil (100% yield) and is characterized by the following spectra: 1H NMR (300 MHz, CDCl3/TMS): delta 5.45-5.25 (m, 6H), 3.63 (t, J=6.6 Hz, 2H), 2.81 (t, J=5.7 Hz, 4H), 2.15-2.00 (m, 4H), 1.62-1.45 (m, 3H), 1.42-1.20 (m, 10H), 0.98 (t, J=7.7 Hz, 3H). 13C NMR (75 MHz, CDCl3/TMS): delta 131.7, 130.1, 128.1, 127.5, 126.9, 62.9, 32.7, 29.6, 29.5, 29.4, 29.2, 27.2, 25.7, 25.6, 25.5, 20.5, 14.3.
100% With lithium aluminium tetrahydride; sodium sulfate; In tetrahydrofuran; at 0 - 20℃; for 4h;Inert atmosphere; An oven-dried 100 mL round bottomed flask was charged with lithium aluminum hydride (2.04 g, 53.87 mmol) in anhydrous THF (20 mL). The flask was cooled to 0 C. with an ice-water bath. To this suspension was added dropwise a solution of ALA acid (5.00 g, 17.96 mmol) in THF (20 mL) via syringe under argon. When the addition was complete, the mixture was allowed to warm to RT and stirred for 4 h. The reaction was then quenched at 0 C. by slow dropwise addition of saturated aqueous solution of sodium sulfate (10 mL). The mixture was allowed to stir for 0.5 h at RT and then filtered through a Buchner funnel. The residue was rinsed with THF. The filtrate and washings were combined and concentrated under reduced pressure to obtain 4.75 g of ALA alcohol as a colorless oil (100%), and is further characterized by: 1H NMR (300 MHz, CDCl3/TMS): delta 5.45-5.25 (m, 6H), 3.63 (t, J=6.6 Hz, 2H), 2.81 (t, J=5.7 Hz, 4H), 2.15-2.00 (m, 4H), 1.62-1.45 (m, 3H), 1.42-1.20 (m, 10H), 0.98 (t, J=7.7 Hz, 3H). 13C NMR (75 MHz, CDCl3/TMS): delta 131.7, 130.1, 128.1, 127.5, 126.9, 62.9, 32.7, 29.6, 29.5, 29.4, 29.2, 27.2, 25.7, 25.6, 25.5, 20.5, 14.3.
With lithium aluminium tetrahydride; In tetrahydrofuran; at 5℃; for 3.25h;Inert atmosphere; Cooling with ice; Lithium aluminum hydride powder (3.33 g, 0.877 mol) was transferred to a 500 mL flask under argon atmosphere. Anhydrous THF (120 mL) was added and the flask cooled in an ice/water bath. Alpha-linolenic acid (10.0 g, 0.036 mol) in THF (40 mL) was added drop-wise over 15 minutes, and the mixture stirred for three hours at 5 C. under argon. After 3 hours, the reaction was quenched by drop-wise addition of saturated sodium sulfate (15 mL) over 30 minutes. Anhydrous sodium sulfate (25 g) was added and the mixture stirred for 30 minutes at RT. The solids were removed by filtration, washing with THF (20 mL). The THF filtrate was further dried over anhydrous sodium sulfate, filtered, and concentrated. The crude ALA-alcohol (9.1 g, 96% yield) was used in the next step without purification and is characterized by the following spectra for the crude product: (0074) 1H NMR (300 MHz, CDCl3/TMS): delta 5.40-5.25 (m, 6H), 3.641 (t, 2H, J=6.6 Hz), 2.81 (m, 4H), 2.11-2.04 (m, 4H), 1.60-1.50 (m, 2H), 1.50-1.20 (m, 12H), 0.97 (t, 3H, J=7.5 Hz).
  • 16
  • [ 463-40-1 ]
  • [ 112965-21-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h; Dicyclohexylcarbodiimide (DCC) (33.3 mg; 0.16 mmol) and 4- (dimethylamino) -pyridine (DMAP) (1.975 mg; 0.016mmol) were added into a solution of calcipotriol (100 mg; 0.24 mmol) in dry CH2C12 (20 ml). The mixture was stirred at 0°C and a solution of linolenic acid (45 mg; 0.1615mmol) or y-linolenic acid (45 mg; 0.1615mmol) in dry CH2C12 (2 ml) was added dropwise under nitrogen atmosphere. The mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with 0.5N HCI, saturated NaHC03 solution, water and then dried (with MgS04). The solvent was evaporated under reduced pressure, and the residue was chromatographed on silica gel (eluting with 1 % chloroform in methanol). ¹H NMR spectra were recorded on a Bruker DMX-500 operating at 500.1 MHz, and chemical shifts are reported in parts per million (8) using TMS as the internal standard. H-NMR (CDC13): No. =5.33-5.40 (m, 6H), 5.00 (s, 1 H), 4.65-4.75 (m, 1 H), 4.45 (bs, 1 H), 4.25 (bs, 1 H), 3.42-3.55 (m, 4), 2.70-2.90 (m, 4H). TLC (5% MeOH in CHC13): Rf =0.33. LC-ESI-MS: m/z =672.2.
  • 17
  • [ 463-40-1 ]
  • [ 94802-00-3 ]
YieldReaction ConditionsOperation in experiment
62% Literature reference for Barton decarboxylation/bromination (Loreau et al., 2000). Oxalyl chloride ((COCl)2), (0.17 mL, 2.0 mmol) and a catalytic amount of DMF (14 muL) were added to a stirred solution of 99% isomerically pure (Z,Z,Z)-linolenic acid 19 (0.55 mL, 1.8 mmol) and CH2Cl2 (4 mL). The reaction mixture was left to stir at reflux temperature under an argon atmosphere for 6 hours and then cooled to RT. The solvent was removed under reduced pressure to obtain a yellow liquid (0.569 g) which was not further purified. 4-Dimethylaminopyridine (DMAP) (22 mg, 0.18 mmol), 2-mercaptopyridine N-oxide, sodium salt (0.325 g, 2.18 mmol) and bromotrichloromethane (CBrCl3) (6.0 mL) were added to an oven-dried RBF with a stir bar and placed under an argon atmosphere. The reaction mixture was heated to reflux temperature and the acyl chloride generated above in CBrCl3 (4.0 mL) was added drop-wise. The solution was left to heat at reflux for 2 h and was then allowed to cool to RT. The mixture was diluted with diethyl ether (20 mL), then brine (20 mL) was added, the layers were separated and the aqueous layer was extracted with diethyl ether (2×20 mL). The combined organic layers were washed with water (20 mL) and dried (MgSO4). Column chromatography on silica gel (1:5 EtOAc:Hexanes) followed by concentration in vacuo yielded 20 (347 mg, 1.11 mmol, 62%) as a pale yellow liquid. Rf=0.52 (hexanes). Spectral data for 20: 1H NMR (CDCl3, 400 MHz): delta 5.32-5.40 (m, 6H), 3.40 (t, 2H, J=8.0 Hz), 2.81, (t, 4H, J=8.0 Hz), 2.07 (m, 4H), 1.85 (m, 2H), 1.30-1.45 (m, 8H), 0.98 (t, 3H, J=8.0 Hz). 13C NMR (CDCl3, 100 MHz): delta 131.9, 130.2, 128.3, 128.2, 127.8, 127.1, 33.9, 32.8, 29.5, 29.1, 28.6, 28.1, 27.2, 25.6, 25.5, 20.5, 14.3. IR (neat, cm1): 3009 (m), 2962 (m), 2929 (s), 2854 (m), 1460 (m), 1438 (m), 1395 (w), 1251 (m), 1066 (w). MS (EI, 70 eV): m/z 55, 67, 79 (base peak), 93, 95, 108, 121, 135, 149, 201, 256, 258, 283, 285, 312 (M+, 79Br), 314 (M+, 81Br).
  • 18
  • [ 463-40-1 ]
  • [ 301-00-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N,N'-diisopropylethylamine / CHCl3 / 1 h / 0 °C 2: t-BuOK / 25 °C
Multi-step reaction with 2 steps 1: CHCl3 / 1 h / 45 °C 2: 4 h / Ambient temperature
  • 19
  • [ 463-40-1 ]
  • [ 822-18-4 ]
YieldReaction ConditionsOperation in experiment
83% 3. Preparation of Sodium Salt of alpha-Linolenic Acid The starting material alpha-linolenic acid has an extremely low solubility in water, so to facilitate action as an enzyme substrate, the alpha-linolenic acid was converted to a sodium salt. That is, 530 mg of sodium carbonate was dissolved in 10 ml of purified water and warmed to 55C, 278 mg of alpha-linolenic acid (made by Nacalai Tesque) was dropwise added thereto and the mixture was stirred for 3 hours. After the end of the reaction, an ion exchange resin (Dowex 50W-X8 (H+form) (made by Dow Chemical)) was used for neutralization, whereby a precipitate was produced. The resultant product was filtered to separate the resin which was then dissolved by MeOH, the solvent was then distilled off under reduced pressure. The product obtained was recrystallized with isopropanol to obtain a desired sodium salt of alpha-linolenic acid (250 mg,83%).
  • 20
  • denatonium hydroxide [ No CAS ]
  • [ 463-40-1 ]
  • [ 890843-17-1 ]
YieldReaction ConditionsOperation in experiment
100% In methanol; at 30 - 60℃; for 1 - 2h; EXAMPLE 6; - Preparation of fatty derivative salts from pure quaternary hydroxide (denatonium linolenate); 50 grams (0.1462 mol) of denatonium hydroxide was dissolved in 50 ml of methanol at 30-45 C. A solution of 40.7 gram (0.1462 mol i.e. 1 mole linolenic acid against 1 mol denatonium hydroxide) of linolenic acid in 50 ml of methanol was added at 30-45 C, and the thus obtained mixture was stirred for 1 - 2 hours at 45- 60 C temperature. The solvent was then distilled off up to thick brownish semi solid mass. 93 grams of denatonium linolenate was obtained with a quantitative yield. (Assay = 99.11%, S' Ash = 0.09%).
  • 21
  • [ 463-40-1 ]
  • [ 107-15-3 ]
  • [ 112705-56-3 ]
YieldReaction ConditionsOperation in experiment
100% With dmap; dicyclohexyl-carbodiimide; In chloroform; at 20℃; for 16h; 793.3 mg of ethylene diamine (13.2 mmol) was added into 1.2 ml of linolenic acid (4 mmol), DCC (1.65 g, 8 mmol), NHS (1.224 g, 8 mmol) and DMAP (0.325 g, 4 mmol) in 10 ml of chloroform. The mixture was stirred for 16 hours at room temperature. The solvent was then evaporated. The mixture was dissolved in 10 ml chloroform and washed twice with 7 ml Brine. The chloroform layer was dried over magnesium sulfate anhydrous, filtered and evaporated. The crude product weighed 2.57 g (crude yield 100%). The product was used for conjugation without further purification.
  • 22
  • [ 463-40-1 ]
  • [ 100-79-8 ]
  • [ 57156-93-1 ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 16h; General procedure: For reaction 1-To a solution of the desired free fatty acid (1.0equivalent) and 1,2-isopropylideneglycerol (1.0 equivalent) inanhydrous dichloromethane (CH 2 Cl 2 , 1.5 ml) maintained at0 C, N,N-dimethyl-4-aminopyridine (0.25 equivalent) andEDC HCl (1.0 equivalent) was sequentially added. The reactionmixture was warmed to room temperature and stirred for 16 h.Upon disappearance of starting compound observed on TLC,the reaction was quenched with saturated sodium bicarbonate(NaHCO 3 ) and extracted three times with CH 2 Cl 2 . The combinedorganic layer was dried over sodium sulfate (Na 2 SO 4 ) and filtered,and the filtrate was concentrated. The crude residue was purifiedby column chromatography using 5% ethyl acetate/hexane as aneluent to afford the corresponding fatty acid ester. For reaction 2-Amberlyst-15 (Hform, 0.5 equivalent) wasadded to a solution of fatty acid ester (1.0 equivalent) in MeOH.The resulting reaction mixture was stirred for 16 h at roomtemperature. After completion of reaction (TLC analysis),Amberlyst-15 was filtered off, and the filtrate was evaporatedunder reduced pressure. The crude residue was purified by col-umn chromatography using 40% ethyl acetate/hexane as an elu-ent to afford the corresponding 1-MAG lipid. The detailed syn-thesis and compound characterization data of each individual1-MAG lipid can be found in the supporting information.
  • 23
  • [ 67-56-1 ]
  • [ 112-79-8 ]
  • 9,12-octadecadienoic acid [ No CAS ]
  • [ 373-49-9 ]
  • [ 506-30-9 ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
  • [ 463-40-1 ]
  • [ 112-62-9 ]
  • [ 29972-79-0 ]
  • [ 112-39-0 ]
  • [ 112-61-8 ]
  • [ 1120-28-1 ]
  • [ 2030-83-3 ]
  • [ 25915-47-3 ]
  • [ 57568-16-8 ]
  • [ 62402-77-1 ]
  • [ 1152412-76-4 ]
  • [ 18899-19-9 ]
  • [ 42714-72-7 ]
  • [ 42448-90-8 ]
  • 5-tridecene [ No CAS ]
  • [ 5557-31-3 ]
  • [ 13481-97-5 ]
  • 9-eicosenoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: Elaidic Acid; 9,12-octadecadienoic acid; 9-hexadecenoic acid; Arachidic acid; 1-hexadecylcarboxylic acid; stearic acid; 9,12,15-octadecatrienoic acid at 50 - 75℃; for 8 - 72h; Neat (no solvent); Stage #2: With ethyl vinyl ether Stage #3: methanol for 1h; Heating / reflux; 2; 3; 4; 8; 9; 10 Synthesis of diacids 19a-19d (FIG. 4) from soy fatty acids (SFA): SFA (16b (Table 3) 2.5 g, 8.9 mmol) and ruthenium catalyst 2 (7.5 mg, 0.9 mmol) were added to a 25 mL, 2-neck round bottom flask under a nitrogen flow. The reaction mixture was stirred and heated at 53° C. and after 2 hours a precipitate formed. After a total of 8 h reaction, the reaction was quenched with ethyl vinyl ether (3 mL) and the reaction mixture transferred to a 50 mL 1-neck flask. The solvent was removed under reduced pressure and the dried product residue methylated with methanol (35 mL) containing conc. sulfuric acid (10 drops). The resulting mixture was heated to reflux for 1 hour, cooled to room temperature, quenched with 50 mL of saturated Na2CO3, extracted with ethyl ether (2×75 mL) and the combined ether layers washed with water (3×50 mL). The organic layer was dried with MgSO4, filtered, and the solvent removed under reduced pressure. The GC trace of the total methylated product is shown in FIG. 4A. The crude methylated product (1 g) was purified by silica gel chromatography column using hexane:ethyl acetate (95:5 v/v) as eluent to give 52 mg of a hydrocarbon fraction (17a-17f, FIG. 5) as a colorless liquid; 500 mg of mixed unsaturated and saturated fatty methyl esters (18a-18g, FIG. 5); and 427 mg of unsaturated dicarboxylate methyl esters (compounds 19a-19d, FIG. 5). GC chromatograms for the isolated fractions are shown in FIGS. 4B-D, respectively. The GC/MS spectrum of the methyl esters of 19a-19d showed [M]+ ions at m/z 340 (19a), m/z 354 (19b), m/z 368 (19c), and m/z 382 (19d). The proposed structures corresponding to these molecular [M]+ ions are shown in FIG. 5. The 1H NMR spectrum of methylated diacids 19a-19d (CDCl3, 200 MHz) had signals at: δ 5.37 (m, -CHCH-, 2H), 3.66 (s, -CH2CO2CH3, 6H), 2.3 (t, J=7.2 Hz & 7.8 Hz, -CH2CO2CH3, 4H), 1.97 (m, 4H), 1.61 (m, 5H) 1.29 (s, 15H). 13C NMR (CDCl3, 50 MHz): δ 174.2 (s, -CO2CH3), 130.4 (s, -CHCH-), 51.4 (s, -CH2CO2CH3), 34.2 (s), 32.6 (s), 29.7 (s), 29.2 (s), 29 (s), 25 (s). GC/MS analysis indicated that the diacids generated were predominately C18 fatty acids; Synthesis of diacids (19a-19d) from rapeseed fatty acids (RFA): RFA ((16c, (Table 3) 2.5 g, 8.9 mmol) were metathesized with catalyst 2 (7.5 mg, 8.8 mmol) at 53° C. After 2 h reaction a significant amount of precipitate was observed in the reaction mixture. After an additional 6 h reaction the acid mixture was isolated and methylated as described above. GC trace of the total methylated product is shown in FIG. 6B. The crude product (1 g) was purified by silica gel column to give 188 mg of a hydrocarbon mixture (17a-17f, FIG. 4), 420 mg of unsaturated fatty methyl esters (18a-18g, FIG. 4), and 390 mg of unsaturated dicarboxylate methyl esters (19a-19d, FIG. 4). GC/MS of the methyl esters of diacids 19a-19d gave [M]+ ions at m/z 340 (19a), m/z 354 (19b), m/z 368 (19c), m/z 382 (19d). 1H NMR of methylated diacids 19a-19d (CDCl3, 200 MHz): δ 5.37 (m, -CHCH-, 2H), 3.66 (s, -CH2CO2CH3, 6H), 2.3 (t, J=7.2 Hz & 7.8 Hz, -CH2CO2CH3, 4H), 1.97 (m, 4H), 1.61 (m, 5H) 1.29 (s, 15H). 13C NMR (CDCl3, 50 MHz): δ 174.4 (s, -CO2CH3), 130.5 (s, -CHCH-), 51.6 (s, -CH2CO2CH3), 34.3 (s), 32.7 (s), 29.7 (s), 29.3 (s), 29.1 (s), 25.1 (s). GC and GC/MS showed that the diacids were predominantly C18 chain-length and that 19a predominated (FIG. 6B).
  • 24
  • [ 67-56-1 ]
  • [ 112-79-8 ]
  • 9,12-octadecadienoic acid [ No CAS ]
  • [ 373-49-9 ]
  • [ 506-30-9 ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
  • [ 463-40-1 ]
  • [ 112-62-9 ]
  • [ 29972-79-0 ]
  • [ 112-39-0 ]
  • [ 112-61-8 ]
  • [ 1120-28-1 ]
  • [ 2030-83-3 ]
  • [ 25915-47-3 ]
  • [ 57568-16-8 ]
  • [ 62402-77-1 ]
  • [ 1152412-76-4 ]
  • [ 18899-19-9 ]
  • [ 42714-72-7 ]
  • 5-tridecene [ No CAS ]
  • [ 13481-97-5 ]
  • 9-eicosenoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: Elaidic Acid; 9,12-octadecadienoic acid; 9-hexadecenoic acid; Arachidic acid; 1-hexadecylcarboxylic acid; stearic acid; 9,12,15-octadecatrienoic acid at 50 - 75℃; for 8 - 72h; Neat (no solvent); Stage #2: With ethyl vinyl ether Stage #3: methanol for 1h; Heating / reflux; 2 The self-metathesis of SFA also was carried out as above on a 50 g scale in a 3-neck, 250 mL round bottom flask equipped with a mechanical stirrer. The crude acid product obtained was fractionally distilled at 0.5 mm Hg. From 35.5 g of crude acid product the following fractions were obtained: a hydrocarbon fraction (17a-17d, 3 g) as a colorless oil over the temperature range of 110° to 120° C.; a monocarboxylic acid fraction (18a-18g, 19 g) over the temperature range of 140° to 210° C., which solidified to a white solid (m. p.=36-38° C.); and a light brown solid residue composed primarily of diacids (19a-19d, 14 g). The diacid fraction, which contained <10% mono-fatty acids (by GC), was purified by recrystallization from a mixture of ethyl acetate (30 mL) and hexane (100 mL) at 3° C. to give diacids 19a-19d as a light brown solid [m. p.=97.5-99.5° C.] in an isolated yield of 12 g (73%). 1H NMR of diacids 19a-19d (CD3OD, 200 MHz): δ 5.35 (m, -CHCH-, 2H), 2.28 (t, J=7.2 Hz & 7.6 Hz, -CH2CO2H, 4H), 1.98 (m, 4H), 1.60 (m, 4H), 1.32 (m, 16H). 13C NMR (CD3OD, 50 MHz): δ 177.8 (s, CO2H), 131.7 (s, CHCH), 35.1 (s), 33.8 (s), 30.9 (s), 30.4 (s), 30.2 (s), 26.2 (s). GC and GC/MS showed that the diacids were predominantly C18 fatty acids.
  • 25
  • [ 67-56-1 ]
  • [ 112-79-8 ]
  • 9,12-octadecadienoic acid [ No CAS ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
  • [ 463-40-1 ]
  • [ 112-62-9 ]
  • [ 29972-79-0 ]
  • [ 112-39-0 ]
  • [ 112-61-8 ]
  • [ 1120-28-1 ]
  • [ 2030-83-3 ]
  • [ 25915-47-3 ]
  • [ 57568-16-8 ]
  • [ 62402-77-1 ]
  • [ 1152412-76-4 ]
  • [ 42714-72-7 ]
  • 5-tridecene [ No CAS ]
  • [ 5557-31-3 ]
  • [ 13481-97-5 ]
  • 9-eicosenoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: Elaidic Acid; 9,12-octadecadienoic acid; 1-hexadecylcarboxylic acid; stearic acid; 9,12,15-octadecatrienoic acid at 53℃; for 20h; Neat (no solvent); Stage #2: With ethyl vinyl ether Stage #3: methanol 2; 15 Synthesis of diacids (19a-19d) from linseed acids (LFA): LFA (16e (Table 3), 2.5 mg, 8.9 mmol) were metathesized with catalyst 2 (7.5 mg, 8.8 mmol) as described for SFA. Only a small amount of diacid precipitate was observed after 12 h reaction. The reaction was worked up and methylated as above. The GC chromatogram for this methyl ester product is shown in FIG. 6D. 1 g of the crude methylated product was separated into hydrocarbon, mono fatty acid ester, and di-fatty acid ester fractions by silica chromatography. The diester fraction was analyzed by GC/MS and gave [M]+ ions for dimethyl esters of 19a-19d at: m/z 340 (19a); m/z 354 (19b); m/z 368 (19c); m/z 382 (19d); with diester 19a predominating.
  • 26
  • [ 463-40-1 ]
  • [ 141-43-5 ]
  • (Z,Z,Z)-octadeca-9,12,15-trienoic acid (2-hydroxyethyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% General procedure: These compounds were synthesized according to the procedure described previously with slight modifications (El-Faham and Albericio, 2010) The appropriate acid (0.15 mmol), (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluoro phosphate (COMU, 64.2 mg, 0.15 mmol), and DIPEA (0.05 ml, 0.30 mmol) were dissolved in anhydrous CH2Cl2 (0.5 ml) and CH3CN (2.5 ml) and the resulting orange-red solution was stirred at rt for 10 min under a nitrogen atmosphere. Ethanolamine (3) (0.15 mmol) in CH3CN (0.2 ml) was then injected into the reaction mixture and vigorous stirring at rt was continued until TLC (CH2Cl2/MeOH 98:2) confirmed the completion of the reaction (3-6 h). The reaction mixture was diluted with CH2Cl2 (3 ml) and the resulting mixture was washed with 5% HCl, saturated NaHCO3 and brine. The organic layer was collected, dried over anhydrous Na2SO4, filtered. The solvent was evaporated under reduced pressure and crude purified by flash chromatography.
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 27
  • [ 50-23-7 ]
  • [ 463-40-1 ]
  • [ 1207627-91-5 ]
YieldReaction ConditionsOperation in experiment
59% With Candida antarctica lipase B In ethanol; toluene at 110℃; regioselective reaction;
  • 28
  • [ 51-61-6 ]
  • [ 463-40-1 ]
  • [ 105955-13-3 ]
YieldReaction ConditionsOperation in experiment
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 29
  • [ 50-67-9 ]
  • [ 463-40-1 ]
  • [ 345663-12-9 ]
YieldReaction ConditionsOperation in experiment
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 30
  • [ 1196-92-5 ]
  • [ 463-40-1 ]
  • Linvanil [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 31
  • [ 35320-23-1 ]
  • [ 463-40-1 ]
  • [ 1282617-76-8 ]
YieldReaction ConditionsOperation in experiment
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 32
  • [ 616-30-8 ]
  • [ 463-40-1 ]
  • [ 1024589-97-6 ]
YieldReaction ConditionsOperation in experiment
General procedure: All fatty acid amides with different acyl chains and amine heads were synthesized using the same procedure but with different precursor compounds. 2-(1H-Benzotriazole-1-yl)-1,2,3,3-tetramethyluronium tetrafluoroborate (TBTU, 1 equiv) was added to a mixture of compound C1 (1 equiv) and triethylamine (TEA, 2 equiv) in EtOAc. After stirring for 1 h at room temperature, isopropylamine (2 equiv) was added and the reaction mixture was stirred for 12 h. The mixture was washed with water, dried and concentrated to give a residue that was purified by reversed-phase HPLC (YMC ODS-H80) eluting with 80% aqueous CH3CN to yield compound 1 (1.5 mg, 63%);
  • 33
  • [ 463-40-1 ]
  • [ 1357286-91-9 ]
  • [ 1357286-92-0 ]
YieldReaction ConditionsOperation in experiment
89% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃;Inert atmosphere; General procedure: compound 8 ( 0.148 g, 0.0002 mol) was dissolved in anhydrous dichloromethane (5 mL); stearic acid (0.0682 g, 0.00024 mol), dicyclohexylcarbodiimide (0.0466 g, 0.00024 mol) and DMAP (0.0024 g, 0.00002 mol) were added under argon; the reaction mixture was stirred overnight at room temperature; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 10 (0.176 g, 0.000184 mol, 92%).
  • 34
  • [ 463-40-1 ]
  • [ 152698-45-8 ]
  • [ 651306-09-1 ]
YieldReaction ConditionsOperation in experiment
84% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at -5℃;Inert atmosphere; General procedure: compound 5 ( 0.19 g, 0.0005 mol) was dissolved in anhydrous dichloromethane (5 mL); linolenic acid (0.14 g, 0.0005 mol), dicyclohexylcarbodiimide (0.102 g, 0.0005 mol) and DMAP (0.006 g, 0.00005mol) were added under argon at -5C; the reaction mixture was stirred overnight at -5C; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 8 (0.296 g, 0.0004 mol, 86%).
  • 35
  • [ 463-40-1 ]
  • [ 28069-18-3 ]
  • [ 1357286-86-2 ]
YieldReaction ConditionsOperation in experiment
94% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃;Inert atmosphere; compound 5 ( 0.19 g, 0.0005 mol) was dissolved in anhydrous dichloromethane (5 mL); linolenic acid (0.29 g, 0.0010 mol), dicyclohexylcarbodiimide (0.204 g, 0.0010 mol) and DMAP (0.012 g, 0.00010mol) were added under argon; the reaction mixture was stirred overnight at room temperature; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 6 (0.406 g, 0.00043 mol, 94%). Spectral data identical to the literature data.12 HRESIMS m/z 965.5591 [M+Na]+ (calcd for C53H82O14Na, 965.5602).
  • 36
  • [ 463-40-1 ]
  • [ 28069-18-3 ]
  • [ 651306-11-5 ]
YieldReaction ConditionsOperation in experiment
86% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at -5℃;Inert atmosphere; compound 5 ( 0.19 g, 0.0005 mol) was dissolved in anhydrous dichloromethane (5 mL); linolenic acid (0.14 g, 0.0005 mol), dicyclohexylcarbodiimide (0.102 g, 0.0005 mol) and DMAP (0.006 g, 0.00005mol) were added under argon at -5C; the reaction mixture was stirred overnight at -5C; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 8 (0.296 g, 0.0004 mol, 86%). 1H-NMR: d 5.35 (1H, m, H-4?), 5.15 (1H, m, H-2?), 4.99 (1H, m, H-3?), 4.49 and 4.47 (each 1H, d, J=7.8 Hz, H-1?), 4.12 (2H, m, H2-6?), 4.10 (2H, m, H2-1), 3.91 (1H, m, H-3a), 3.87 (1H, m, H-5?), 3.86 (1H, m, H-2), 3.65 (1H, m, H-3b), 2.77 (4H, m, bisallylic-H), 2.31 (2H, m, a-methylene of acyl portion), 2.12 (3H, s, OAc), 2.06 (4H, m, vinylic protons), 2.03 (3H, s, OAc), 2.01 (3H, s, OAc), 1.96 (3H, s, OAc), 1.59 (2H, m, b-methylene of acyl portion), 1.35-1.25 (m, aliphatic protons), 0.92 (3H, t, J=7.1 Hz, CH3); HRESIMS m/z 705.3481 [M+Na]+ (calcd for C35H54O13Na, 705.3462).
  • 37
  • [ 463-40-1 ]
  • [ 651306-07-9 ]
  • [ 1357286-93-1 ]
YieldReaction ConditionsOperation in experiment
86% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃;Inert atmosphere; General procedure: compound 8 ( 0.148 g, 0.0002 mol) was dissolved in anhydrous dichloromethane (5 mL); stearic acid (0.0682 g, 0.00024 mol), dicyclohexylcarbodiimide (0.0466 g, 0.00024 mol) and DMAP (0.0024 g, 0.00002 mol) were added under argon; the reaction mixture was stirred overnight at room temperature; after evaporation under reduced pressure, the mixture was purified by silica gel chromatography using a gradient of petroleum ether/diethyl ether to give compound 10 (0.176 g, 0.000184 mol, 92%).
  • 38
  • [ 64-17-5 ]
  • [ 463-40-1 ]
  • [ 122-51-0 ]
  • [ 1191-41-9 ]
YieldReaction ConditionsOperation in experiment
> 99% With immobilized Candida antarctica Lipase B; In neat (no solvent); at 60℃; for 4h;Green chemistry; Enzymatic reaction; TEOF 12 ml (0.072 mol) and 1 g of Novozym 435 were added to ALA 20 g (0.072 mol). The mixture added of 10 mul of ethanol and incubated at 60 C under shaking at 300 rpm. After 4 h the GC analysis evidenced the complete conversion of the substrate, and the reaction was stopped by filtering off the enzyme. The obtained oil, kept under vacuum (2 mbar) for 1 h at rt, furnished 22 g of ALA ethyl ester (in >99% yield), which nature was confirmed by comparison in GC analysis with an authentic sample.
  • 39
  • [ 3380-34-5 ]
  • [ 463-40-1 ]
YieldReaction ConditionsOperation in experiment
In (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid; ethyl acetate; Example 2 Dyneema Purity Braid Comprising Alpha-Linolenic Acid: Ref-HPPE-L-TRI-2.9 Dyneema Purity braids (8*1*110) was dip-coated (10 min at 23 C.) in a 6.0 g/L alpha-linolenic acid solution in ethyl acetate containing 2.9 g/L (grams per liter) <strong>[3380-34-5]triclosan</strong> (see Table 2). The resulting braid was dried at 23 C.
  • 40
  • [ 463-40-1 ]
  • [ 60-81-1 ]
  • [ 1421589-33-4 ]
YieldReaction ConditionsOperation in experiment
94% With Novozyme 435; In acetone; at 45℃;Molecular sieve; Enzymatic reaction; General procedure: To flame dried 3 A molecular sieves, in round bottom flask, was added phloridzin (0.500 g; 1.15 mmol), stearic acid (1.62 g, 5.72 mmol), Novozyme 435 (1.30 g). It was followed by the addition of dry acetone (5 ml) and the mixture was stirred and heated at 45 C for 12-24 h. The progress of reaction was monitored by thin layer chromatography (TLC), followed by staining with anisaldehyde spray reagent and then heating at 110 C. After completion of reaction, it was filtered, evaporated and passed through column chromatography (acetone/toluene; 35:75 to 50:50) to get the pure stearic acid ester (2) of phloridzin. All other reactions followed the same procedure and produced esters 3-7 and 9-14, with yields in the range of 81-98%. The pure compounds were then analyzed by IR, 1H NMR and 13C NMR spectroscopy. All other compounds were prepared by the same method
  • 41
  • [ 482-35-9 ]
  • [ 463-40-1 ]
  • [ 1421589-37-8 ]
YieldReaction ConditionsOperation in experiment
91% With Novozyme 435; In acetone; at 45℃;Molecular sieve; Enzymatic reaction; General procedure: To flame dried 3 A molecular sieves, in round bottom flask, was added phloridzin (0.500 g; 1.15 mmol), stearic acid (1.62 g, 5.72 mmol), Novozyme 435 (1.30 g). It was followed by the addition of dry acetone (5 ml) and the mixture was stirred and heated at 45 C for 12-24 h. The progress of reaction was monitored by thin layer chromatography (TLC), followed by staining with anisaldehyde spray reagent and then heating at 110 C. After completion of reaction, it was filtered, evaporated and passed through column chromatography (acetone/toluene; 35:75 to 50:50) to get the pure stearic acid ester (2) of phloridzin. All other reactions followed the same procedure and produced esters 3-7 and 9-14, with yields in the range of 81-98%. The pure compounds were then analyzed by IR, 1H NMR and 13C NMR spectroscopy. All other compounds were prepared by the same method
  • 42
  • [ 3731-52-0 ]
  • [ 463-40-1 ]
  • [ 37140-75-3 ]
YieldReaction ConditionsOperation in experiment
49% General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1?-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153muL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87 [lit.45 mp 94.5-95, and46 fp 95.1]; 1H NMR (400MHz, CDCl3) delta 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) delta 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346.
  • 43
  • [ 463-40-1 ]
  • [ 100-46-9 ]
  • (9Z,12Z,15Z)-N-benzyloctadeca-9,12,15-trienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1?-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153muL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87 [lit.45 mp 94.5-95, and46 fp 95.1]; 1H NMR (400MHz, CDCl3) delta 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) delta 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346.
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 15℃; for 20h; 0.02 mol of HOAt, 0.02 mol of EDC · HCl and 0.02 mol of DIPEA were weighed in 30 mL of DCM and 0.01 mol of benzylamine, 0.01 mol of linolenic acid was added and stirred at 15 C for 20 h. 50 mL of deionized water was added and stirred at room temperature 30 min, the filtered product was dried in vacuo to give the product
  • 44
  • [ 5071-96-5 ]
  • [ 463-40-1 ]
  • [ 883715-23-9 ]
YieldReaction ConditionsOperation in experiment
80% General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1?-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153muL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87 [lit.45 mp 94.5-95, and46 fp 95.1]; 1H NMR (400MHz, CDCl3) delta 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) delta 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346.
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; 0.02 mol of HOAt, 0.02 mol of EDC · HCl and 0.02 mol of DIPEA were weighed in 30 mL of DCM and 0.01 mol of m-methoxybenzylamine, 0.01 mol of linolenic acid was added and stirred overnight at room temperature; 50 mL of deionized water was added, Stirring for 30min, adding chloroform extraction, extraction layer nitrogen blowing to the volume is no longer reduced products
  • 45
  • [ 463-40-1 ]
  • [ 302-27-2 ]
  • 14-O-debenzoylaconitine [ No CAS ]
  • C52H75NO12 [ No CAS ]
  • [ 466-24-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium chloride In water
  • 46
  • [ 463-40-1 ]
  • [ 87745-27-5 ]
  • [ 1513888-75-9 ]
  • 47
  • [ 463-40-1 ]
  • [ 4136-95-2 ]
  • [ 1620745-10-9 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 25℃; for 0.5h; General procedure: Hyaluronic acid (5 g, 12.5 mmol) was dissolved overnight in 100 ml of distilled water. To that solution 50 ml of THF were slowly added. After the solution was homogeneous, triethylamine (3.5 ml, 25 mmol) and DMAP (0.015 g, 0.125 mmol) were added and the mixture was stirred until a clear solution was obtained. At the same time and in a second reaction flask, the fatty acid was activated using the molar ratio described in Tables 1 and 2. The molar equivalents of the fatty acid as resumed in Tables 1 and 2 were dissolved in tetrahydrofurane (10 ml). After that, TEA (5 ml, 25 mmol) were added, followed by one molar equivalent of 2,4,6-trichlorobenzoyl chloride (TCBC). The formation of the aliphatic aromatic anhydride was carried out for 30 min at room temperature (25C). Then, the solution containing the mixed anhydride was added to the solution containing the polysaccharide. The mixture is allowed to react for 3 h at room temperature under vigorous stirring to ensure a good homogenization of the components. The crude product was isolated by precipitation with the addition of 100 ml of distilled water and a super-saturated solution of sodium chloride. After that the product was washed with an excess of anhydrous isopropanol (250 ml). The product was washed again with solutions of isopropanol: water (85%, v/v, 4× 250 ml). Finally, the precipitate was washed two more times with absolute isopropanol. The white precipitate was decanted and dried in an oven at 40C for at least 24 h. Yields of the reaction are resumed in Tables 1 and 2.
  • 48
  • [ 463-40-1 ]
  • [ 4064-06-6 ]
  • C30H48O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 16h;Inert atmosphere; To a stirred solution of the commercially available galactose his-acetonide (260 mg, 1.00 rnmol) in dichloromethane (10 mL) at room temp under argon was added linolenic acid (278 mg, 1.0 rnmol), dicyclohexylcarbodiimide (206 mg, 1.0 mmol) and DMAP (24 mg, 0.2 mmoi), the reaction mixture was stirred overnight (ca 16 hours) at room temp. The reaction was cooled to -20 C, and filtered, the filtrated, was and evaporated under reduced pressure and the mixture was purified by silica gel chromatography (8:1 to 2:1 Petrol:Et2O) to afford the compound 146 (438 mg, 0.84 mmol, 84 %) as a colourless oil.
  • 49
  • [ 463-40-1 ]
  • C18H28O10 [ No CAS ]
  • C36H56O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
55.8% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 16h;Inert atmosphere; DCC coupling according to a slightly modified procedure reported in Tetrahedron Lett. 2012, 53. 879. To a stirred solution of the alcohol C (126 mg, 031 inmol) in dichloromethane (6 mL) at room temp under argon was added linolenic acid (94.5 mg, 0.34 mmoi), dicyclohexylcarbodiimide (70.6 mg, 0.34 mmol) and DMAP (8.4 mg, 0.068 mmol). the reaction mixture was stirred overnight (ca 16 hours) at room temp. The reaction was cooled to -20 C, and filttered, the filtrated was and evaporated under reduced pressure and the mixture was purified by silica gel chromatography (8:1 to 4:1 Petrol:EtOAc) to afford the ester D (115 mg, 0.173 mrnol, 55.8 %) as a colourless oil.
  • 50
  • [ 463-40-1 ]
  • [ 2423-13-4 ]
YieldReaction ConditionsOperation in experiment
To a solution of linolenic acid (4.57 ml, 15 mmol, 1 eq) in THF (190 ml) at 0 C was added Lithium Aluminum Hydride (1 M in THF, 22.5 ml, 22.5 mmol, 1.5 eq) dropwise. The solution was allowed to warm to room temperature and was stirred overnight. The reaction was quenched with sequential additions of water (0.85 ml), iN NaOH (0.85 ml), and water (2.6 ml) dropwise. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The crude product was then dissolved in CH2C12 (160 ml). NaHCO3 (8.821 g, 105 mmol, 7 eq) was added followed by Dess-Martin-Periodinane (7.63 g, 18 mmol, 1.2 eq). The mixture was stirred for 2 hours, 15 minutes. It was then diluted in petroleum ether, washed sequentially with saturated NaHCO3 and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product EA-03-aldehyde, a yellow oil, was used without further purification.
  • 51
  • [ 463-40-1 ]
  • [ 79-20-9 ]
  • [ 301-00-8 ]
YieldReaction ConditionsOperation in experiment
With sodium methylate In hexane Heating;
  • 52
  • [ 463-40-1 ]
  • [ 86639-52-3 ]
  • 7-ethyl-cis-9,12,15-octadecaacryloyloxycamptothecin [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With benzotriazol-1-ol; diisopropyl-carbodiimide; In chloroform; for 18h; 1mol7-ethyl -10-hydroxy camptothecin, 1.1mol cis 9, 12, 15-eighteen carbon trienic acid and 1.2molN, N '-diisopropyl carbodiimide dissolved in the 2L in chloroform, 2.1mol1-hydroxy benzotriazole added after dissolving a small amount of chloroform is added to the constant pressure titration funnel in dissolved drug solution, sample reaction after 18 hours, turns on lathe does solvent, the obtained drug powder washed twice with ethyl ether, dissolved in the chloroform after drying, recrystallization to obtain pure target product. Yield: 93%.
  • 53
  • [ 463-40-1 ]
  • [ 118-42-3 ]
  • hydroxychloroquine linolenate [ No CAS ]
YieldReaction ConditionsOperation in experiment
52.5% Under nitrogen protection and cooling in an ice bath,The purity was 70%32.5 mmola-linolenic acid 12.9 g and 220 mL dichloromethane were charged into a 500 mL three-neck round bottom flask,A solution of 4-methylmorpholine, 4-dimethylaminopyridine and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride in that order,After stirring for 30 min, the reaction was allowed to warm to room temperature.In which dichloromethane can be replaced with chloroform, and the catalyst may be replaced with triethylamine, pyridine or 1-hydroxybenzotriazole; the dehydrating agent may be dicyclohexylcarbodiimide,N, N'-diisopropylcarbodiimide or 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride.To the linolenic acid, 16.8 g of hydroxychloroquine (48.8 mmol) was added and the reaction was stirred for 12 hours.100 mL of methylene chloride was added to the flask, and the mixture was heated to 50 C in a water bath. The reaction solution was washed with hydrochloric acid solution, saturated sodium chloride solution and purified water, and the organic phase was dried over anhydrous sodium sulfate and concentrated to give a tan oil.The solution was washed with 200 mL hydrochloric acid solution. The separatory funnel was divided into three phases. The upper layer was a methyl tert-butyl ether phase, The middle layer is an oily substance, and the lower layer is an aqueous phase.The oil was isolated and dissolved in 200 mL of methanol. Activated charcoal was decolorized, decolorized and concentrated to give a yellow oil.Column chromatography on a silica gel with a stationary phase of 200 mesh using dichloromethane / methanol as eluant and a 50: 1 by volume ratio of dichloromethane to methanol as the eluent was concentrated to dryness And 11.3 g of hydroxychloroquineolinolate in a yield of 52.5%.
  • 54
  • [ 463-40-1 ]
  • [ 13734-36-6 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C50H100O26 [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-33-8 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 146982-27-6 ]
  • [ 143824-78-6 ]
  • [ 159857-60-0 ]
  • (Sar)WTLNSAGYLLGPKK(Lys-α-Lnn)K(Lys-MPEG24)-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
For Gal-100, 2-fold of Fmoc-Lys (Mmt)-OH was coupled manually by PyBop method to Rink Amide Clear resin, followed with the coupling of Fmoc-Lys (Boc)-OH and Fmoc-Lys (Aloc)-OH. After all the remaining amino acids were coupled, HAc/TFE/DCM (1:2:7) was added to the resin to remove the Mmt group, and then the resin was neutralized with 10% DIEA/CH2Cl2, and m-dPEG-24 acid was coupled using same method as disclosed for Gal-81. Aloc was deprotected with tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.23 g, 0.2 mmol) in 2.78 mL DCM/AcOH/N-methylmorpholine (NMM) for 2 h. The resin was then washed with CH2Cl2, 0.5% DIEA/CH2Cl2 to remove AcOH, 0.02 M sodium diethyldithiocarbamate solution in NMP and to remove Palladium residues, CH2Cl2. alpha-Linolenic acid was coupled for 20 h. 5 ml TFA/PhOH/Thioanisole/H2O (85/5/5/5) was added to the resin under N2 and protected from light. After 40 min, TFA was evaporated in vacuum and MTBE was added to precipitate the products. The crude peptide was purified by preparative RP-HPLC to give the target peptide Gal-100. For Gal-105, the same synthetic method for Gal-100 was followed, only Boc-Trp (Boc)-OH was used at the N-terminal amino acid.
  • 55
  • Nα-(tert-butoxycarbonyl)-1-methyl-L-tryptophan [ No CAS ]
  • [ 463-40-1 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C50H100O26 [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-33-8 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 146982-27-6 ]
  • [ 159857-60-0 ]
  • WTLNSAGYLLGPKK(Lys-α-Lnn)K(Lys-MPEG24)-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: For Gal-100, 2-fold of Fmoc-Lys (Mmt)-OH was coupled manually by PyBop method to Rink Amide Clear resin, followed with the coupling of Fmoc-Lys (Boc)-OH and Fmoc-Lys (Aloc)-OH. After all the remaining amino acids were coupled, HAc/TFE/DCM (1:2:7) was added to the resin to remove the Mmt group, and then the resin was neutralized with 10% DIEA/CH2Cl2, and m-dPEG-24 acid was coupled using same method as disclosed for Gal-81. Aloc was deprotected with tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.23 g, 0.2 mmol) in 2.78 mL DCM/AcOH/N-methylmorpholine (NMM) for 2 h. The resin was then washed with CH2Cl2, 0.5% DIEA/CH2Cl2 to remove AcOH, 0.02 M sodium diethyldithiocarbamate solution in NMP and to remove Palladium residues, CH2Cl2. alpha-Linolenic acid was coupled for 20 h. 5 ml TFA/PhOH/Thioanisole/H2O (85/5/5/5) was added to the resin under N2 and protected from light. After 40 min, TFA was evaporated in vacuum and MTBE was added to precipitate the products. The crude peptide was purified by preparative RP-HPLC to give the target peptide Gal-100. For Gal-105, the same synthetic method for Gal-100 was followed, only Boc-Trp (Boc)-OH was used at the N-terminal amino acid.
  • 56
  • [ 183133-96-2 ]
  • [ 463-40-1 ]
  • C63H85NO15 [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 25℃; To a 100 mL round bottom flask was added CTX (100 mg, 0.12 mmol) and linolenic acid (34 mg, 0.12 mmol)Was dissolved in 5 mL of anhydrous dichloromethane,EDC · HCl (25 mg, 0.13 mmol) was added,4-dimethylaminopyridine (16 mg, 0.13 mmol) and N, N-diisopropylethylamine (21 L, 0.13 mmol).25 C overnight,And then with 5% citric acid,Saturated sodium bicarbonate,Saturated brine cleaning;The organic phase was dried over anhydrous sodium sulfate,filter,The filtrate was collected and the solvent was removed under reduced pressure.The solid was purified by column chromatography (DCM: MeOH = 200: 1) to give product 2 (115 mg, yield 87%).
  • 57
  • [ 463-40-1 ]
  • [ 63121-18-6 ]
  • (R)-1-O-linolenoyl-3-(tert-butyldimethylsilyl)-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% To a solution of 9 (392 mg,1.90 mmol) and COMU (1-[(1-(Cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholino)]uronium hexafluorophosphate, 1.22 g, 2.85 mmol) in anhydrous CH2Cl2 (10 ml) in a two-neck flask was added a solution of alpha-linolenic acid (500 mg, 1.80 mmol) in anhydrous CH2Cl2 (9 ml) at 0 C. Then iPr2NEt (660 mul, 3.80 mmol) was dropped to the solution at 0 C and stirred for 20 min before solid DMAP (70 mg, 0.57 mmol) was added at 0 C. The mixture was allowed to warm to room temperature and stirred for 7 h. The solution was diluted with a mixture of hexane and EtOAc (10:1, 10 ml), and passed through a short silica-gel column to remove amine and other polar compounds. The eluate was collected and purified again by silica-gel flash column chromatography (hexane/EtOAc = 15:1) to give S1 (310 mg, 37%) as a colorless oil.
  • 58
  • [ 73-32-5 ]
  • [ 463-40-1 ]
  • C24H41NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% a-Linolenic acid (2, 0.88 mmol, 245 mg) was dissolved in tetrahydrofuran (11 ml) with trimethylamine (0.98 mmol, 0.14 ml). Chloroformic acid ethyl ester (0.1 mmol, 0.1 ml) was added while the mixture was stirred at -10 C. After the resulting solution was stirred for 20 min, a 0.3 M aqueous NaOH solution (6.9 ml) containing Ile (1.77 mmol, 232 mg) was added to the solution and stirred for an additional 25 min at room temperature. After evaporation to remove the solvent, the obtained residue was cooled at 0 C, and poured into 1 M HCl, extracted with ethyl acetate, and dried over Mg2SO4. The extract was evaporated and purified by SiO2 gel column chromatography (Kanto Chemical, Tokyo, Japan), which was developed with a mixed solvent of acetic acid/ethyl acetate/n-hexane (1/30/70, v/v). LA-Ile (10) was obtained as a colorless oil (293.2 mg, 85%). FD-HR-MS: found m/z 392.3150 [M+H]+; calculated m/z 392.3165 for C24H42NO3; [alpha]25D +19.8 (c 0.3, CHCl3); 1H-NMR (CDCl3, 270 MHz) d: 11.03 (s, 1H), 6.44 (d, J = 8.6 Hz, 1H), 5.38-5.21 (m, 6H), 4.59 (dd, J = 4.6, 8.6 Hz, 1H), 2.77-2.73 (m, 4H), 2.22 (t, J = 8.1 Hz, 2H), 2.08-1.85 (m, 6H), 1.60-1.38 (m, 3H), 1.22-1.07 (m, 8H), 0.97-0.81 (m, 9H).
  • 59
  • [ 462-08-8 ]
  • [ 463-40-1 ]
  • (9Z,12Z,15Z)-N-(pyridin-3-yl)octadeca-9,12,15-trienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h; General procedure: In a typical synthesis procedure to a solution of 7.08mmol of fatty acid in 50mL of DCM, 8.496mmol of 3-aminopyridine (1.2 equivalents) and 8.496mmol of EDC-HCl (1.2 equivalents) were added and stirred for 12h at room temperature. The reaction mixture was diluted to 100mL with DCM and washed with 50mL water and 1M HCl solution to remove EDC urea, excess EDC-HCl and 3-aminopyridine. Thereafter, DCM fraction was washed with 1M sodium carbonate solution to neutralise any HCl associated with pyridine structure of the product formed.
  • 60
  • [ 463-40-1 ]
  • [ 7646-85-7 ]
  • zinc linolenate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79.4% First step: Activate zinc chloride: Dissolve 1.36 g (1 mol/L) of zinc chloride in a reaction vessel with 10 mL of sterile water. The reaction kettle was placed in a drying oven and heated at 165 C for 30 min, and naturally cooled.Step 2: Activate linolenic acid:1-ethyl-3-(3-dimethylaminopropyl)carbonyldiimide hydrochloride (EDC) 766 mg,460 mg of N-hydroxythiosuccinimide (NHS) and 560 mg of alpha-linolenic acid (alpha-LLA) were dissolved in 5 mL of EMS solvent.The mixture was stirred and activated for 30 min under nitrogen.The third step: complexation reaction:Add 1 mL (136 mg or 1 mM) of activated zinc chloride and 4.5 mL (504 mg or 1.8 mM) of linolenic acid to the reaction kettle.Add 4.5 mL of sterile water and a total of 10 mL of liquid.Mix on a heated magnetic stirrer,The temperature was controlled at 70 C and the reaction was carried out for 3 h. After the completion of the reaction, it was allowed to stand to cool overnight.The fourth step: dialysis washing:The complex reaction solution was placed in a dialysis bag (RC membrane, 1 KD, 38 mm) and diafiltered with 1 L of deionized water for 12 h.Change the deionized water 4 times in the middle.The unbound zinc ions and the like are dialyzed and filtered until the deionized water is clear and transparent.The fifth step: freeze-drying: the dialysis reaction solution was placed in a glass screw sample vial, dried in a vacuum freeze dryer at -45 C, 0.02 mBar, and dried for 72 h to obtain zinc linolenate, and the yield was 79.4%.
  • 61
  • [ 463-40-1 ]
  • [ 480-39-7 ]
  • 5-hydroxy-4-oxo-2-phenylchroman-7-yl-octadeca-9,12,15-trienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% General procedure: A solution of fatty acid (1 eq) in dichloromethane (DCM) at 0 C was added of N,N'-dicyclohexylcarbodiimide (DCC) (1.2 eq) and a catalytic amount of 4-dimethylaminopyridine (DMAP); the obtained mixture was vigorously stirred for 30 min. Then, a solution of pinocembrin in DCM was dripped slowly and the reaction was stirred for 24 h. The reaction progress was monitored by TLC. The mixture was filtered on Celite with DCM; the filtrate was then washed with a cold solution of NaHCO 3 to remove any trace of free acid. The obtained organic layer was then washed with brine and evaporated under reduced pressure to furnish the desired product.
  • 62
  • [ 463-40-1 ]
  • [ 19420-57-6 ]
  • [ 35418-57-6 ]
YieldReaction ConditionsOperation in experiment
77% With 1-methyl-1H-imidazole; 2-methyl-6-nitrobenzoic anhydride; In dichloromethane; at 20℃; for 16h; To a solution of alpha-linolenic acid (1h) (55 mg, 0.198 mmol) in CH2Cl2 (2 mL) were added NMI (0.036 mL, 0.456 mmol) and MNBA (158 mg, 0.459 mmol). After 20 min of stirring at rt, lyso-PC 2a (53 mg, 0.101 mmol) was added. The mixture was stirred at rt for 16 h and concentrated to give a residue, which was purified by chromatography on silica gel (CHCl3/MeOH/H2O = 65:25:1 to 65:25:3) to afford PC 3h (61 mg, 77%): Rf = 0.08(CHCl3/MeOH/H2O = 65:25:1); 1H NMR (400 MHz, CD3OD) delta 0.90 (t, J = 7.2 Hz, 3 H),0.97 (t, J = 7.2 Hz, 3 H), 1.21-1.43 (m), 1.54-1.68 (m, 4 H), 2.02-2.14 (m, 4 H), 2.31 (t, J =7.6 Hz, 2 H), 2.34 (t, J = 7.6 Hz, 2 H), 2.81 (t, J = 6.0 Hz, 4 H), 3.22 (s, 9 H), 3.61-3.68 (m,2 H), 4.00 (t, J = 6.2 Hz, 2 H), 4.17 (dd, J = 12.1, 6.8 Hz, 1 H), 4.23-4.32 (m, 2 H), 4.44 (dd,J = 12.1, 3.0 Hz, 1 H), 5.20-5.27 (m, 1 H), 5.27-5.44 (m, 6 H); 13C NMR (100 MHz, CD3OD)delta 13.2, 13.4, 20.2, 22.4, 24.7, 25.1, 25.2, 26.9, 28.8, 28.90, 28.94, 29.0, 29.2, 29.35, 29.42,29.5, 31.7, 33.6, 33.7, 53.3 (t, J = 3.4 Hz, 3 C), 59.1 (d, J = 4.6 Hz), 62.2, 63.5 (d, J = 4.6Hz), 66.0 (m), 70.4 (d, J = 8.4 Hz), 126.9, 127.5, 127.8, 127.9, 129.7, 131.4, 173.0, 173.4;HRMS (FAB) calcd for C44H83O8NP [(M+H)+] 784.5856, found 784.5893.
  • 63
  • [ 463-40-1 ]
  • [ 1622988-44-6 ]
  • (9,12,15Z)-4-((E)-3,5-bis((triisopropylsilyl)oxy)styryl)phenyl octadeca-9,12,15-trienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 2h;Inert atmosphere; A solution of 49 linolenic acid (ALA; 56 mg, 0.20 mmol) in dry 28 DCM (2.50 mL) was added to the protected resveratrol 24 3 (100 mg, 0.18 mmol) in solution in DCM (2.50 mL). 30 DCC (42 mg, 0.20 mmol) and 31 DMAP (6 mg, 0.05 mmol) were added to the reaction mixture and the solution was left to stir at room temperature under inert atmosphere during 2h (monitored by TLC pentane/34 EtOAc 95:5). Flask was put into the fridge (4 C) for 1h to maximize the amount of DCU crystals. White DCU precipitate was then removed by filtration on frit, rinsed by a few drops of cold DCM. Filtrate was diluted by 10 mL of DCM and washed twice with water (10 mL) and once with brine (10 mL). The organic layer was dried over MgSO4 and evaporated. Purification by silica gel column chromatography (pentane/EtOAc 99.5/5 to 99/1) resulted in 115 mg (76%) of 50 compound 4d as a colorless oil. Rf (pentane/EtOAc 95:5) 0.5.; 1H NMR (500 MHz, CDCl3): deltaH 7.50 (d, J = 8.5 Hz, 2H, H2' and H6'), 7.07 (d, J = 8.5 Hz, 2H, H3' and H5'), 6.98 (d, J = 16.5 Hz, 1 H, H8), 6.92 (d, J = 16.5 Hz, 1H, H7), 6.65 (d, J =2.5 Hz, 2H, H2 and H6), 6.36 (t, J = 2.5 Hz, 1H, H4), 5.39-5.36 (m, 6H, CH=CH), 2.82 (t, J = 6.5 Hz, 4H, CH2 bis-allylic), 2.56 (t, J = 7.5 Hz, 2H, CH2-C=O), 2.10 - 2.06 (m, 4H, CH2 allylic), 1.75 (quint, J = 7.5 Hz, 2H, CH2-CH2-C=O), 1.43-1.21 (m, 14H, CH2-CH2 and CH-Si), 1.11 (d, J = 7.5 Hz, 36 H, CH3-CH), 0.89 (t, J = 7 Hz, 3H, CH3-CH2); 13C NMR (126 MHz, CDCl3) deltaC 172.3, 157.2, 150.2, 138.9, 135.1, 132.1, 132.1, 130.4, 129.1, 128.4, 128.4, 127.9, 127.7, 127.5(2C), 127.2, 121.9(2C), 111.5(2C), 111.4, 34.5, 29.7, 29.3, 29.2, 29.2, 27.3, 25.7, 25.6, 25.0, 20.7, 18.1(6C), 14.4, 12.8(12C)
  • 64
  • [ 524-38-9 ]
  • [ 463-40-1 ]
  • 1,3-dioxoisoindolin-2-yl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With dmap; diisopropyl-carbodiimide; In dichloromethane; at 20℃; for 14h; General procedure: The synthesis of NHPI esters (5a-g) followed Qin and coworkers [17] reported procedures with minor modification. Briefly, a round bottom flask (RBF) charged with PUFA (4, 1 eq.), 2- hydroxyisoindoline-1,3-dione (NHPI, 1 eq.), N, N-dimethylpyridin4-amine (DMAP, 0.1 eq.), diisopropylmethanediimine (DIC, 1 eq.) in dry dichloromethane (solvent, PUFA concentration 0.2 M) was stirred at room temperature for 14 h. The resulting mixture was concentrated in vacuo, and the residue was separated over preparative flash chromatography (SiO2, eluted with EtOAc: hexane 6 : 94 to 10 : 90), to yield the desired product as a colorless oil.
  • 65
  • [ 463-40-1 ]
  • [ 25316-40-9 ]
  • [ 1116566-29-0 ]
YieldReaction ConditionsOperation in experiment
68% General procedure: A solution of carboxylic acid (1 eqv, 0.34mmol) andN,N?-dicyclohexylcarbodiimide (DCC) (1.5 eqv, 106.8mg,0.52mmol) in dry CH2Cl2/DMF (9:1, 28mL) was stirred for15min at 22 C. Then, DMAP (1.1 eqv, 46.4mg, 0.38mmol)and DOX·HCl (1 eqv, 200mg, 0.34mmol) were added andthe red suspension was stirred for 20 h at 22-23 C in thedark. Then reaction mixture was filtered, solid was washedwith CH2Cl2 (2 × 20mL), and next the combined organicphases was washed with 1.5% HCl water solution (2 ×15mL). The organic layer was dried over MgSO4 and afterevaporation of the solvent under reduced pressure the productwas isolated using column chromatography on silica gel andCH2Cl2:MeOH mixture (0-2% MeOH) as an eluent.
  • 66
  • [ 463-40-1 ]
  • [ 25316-40-9 ]
  • C63H85NO13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% General procedure: A solution of carboxylic acid (2 eqv, 0.34 mmol) andN,N?-dicyclohexylcarbodiimide (DCC) (2.5 eqv, 89.0 mg,0.43 mmol) in dry CH2Cl2/DMF (9:1, 14 mL) was stirredfor 15 min at 22 C. Then, DMAP (1.1 eqv, 23.2 mg,0.19 mmol) and DOX·HCl (1 eqv, 100 mg, 0.17 mmol)were added and the red suspension was stirred for 20 h at22-23 C in the dark. Then reaction mixture was filtered,solid was washed with CH2Cl2 (2 × 10 mL), and next thecombined organic phases were washed with 1.5% HClwater solution (2 × 10 mL). The organic layer was driedover MgSO4 and after evaporation of the solvent underreduced pressure the product was isolated using columnchromatography on silica gel and CH2Cl2:MeOH mixture(0-1% MeOH) as an eluent.
  • 67
  • [ 463-40-1 ]
  • [ 85721-33-1 ]
  • 7-[4-(9Z,12Z,15Z)-octadec-9,12,15-trienoyl-piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 22 - 23℃; for 2h; General procedure: To a suspension of CP (0.20g; 0.60mmol) and an appropriate fatty acid (0.60mmol) in dried CH2Cl2 (24ml), the BOP reagent (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate) (0.27g, 0.60mmol) and triethylamine (0.13mL; 0.91mmol) were added. The resulting solution was stirred for 2hat 22-23C. To the obtained reaction mixture, 0.67% HClaq solution (15mL) was added. Next, it was extracted with CH2Cl2 (2×25 mL). The combined organic layers were washed with 1% HClaq solution (4×25 mL) and distilled water (2×25 mL), and then dried over anhydrous MgSO4. After the solvent evaporation, the product was isolated using column chromatography on silica gel (with CH2Cl2:MeOH mixture as an eluent). The final product was washed with diethyl ether (2×2 mL). The structures of all compounds were confirmed by 1H NMR, 13C NMR and MS spectra (see Supplementary material).
  • 68
  • [ 463-40-1 ]
  • donepezil hydrochloride [ No CAS ]
  • donepezil α-linolenic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.71% General procedure: 2.2. Preparation of donepezil ionic liquidsThe ionic liquids described herein were synthesized by metathesisreaction. Docusate sodium, oleate sodium, linoleate sodiumand ibuprofensodium were commercially available compounds. The alpha-linolenicsodium and docosahexaenoic sodium could be prepared by reaction oftheir acid with NaOH. In brief, the solution of NaOH (1 M in water,1.0 mL, 1.0 mmol) was slowly added to the suspension of alpha-linolenicor DHA (1.0 mmol in 10 mL ultrapure water), then the mixture wasstirred at room temperature for 2 h.Donepezil hydrochloride (2.0 mmol) and anionic sodium(2.0 mmol) were dissolved in 40 mL ultrapure water with stirring atroom temperature for 4 h. The products were extracted with dichloromethane,then the dichloromethane phase was washed with ultrapurewater to remove the formed inorganic salt. Silver nitrate test was usedto confirm that the chloride ions was completely removed. Dichloromethanewas removed on a rotary evaporator at 50 C for 2 h, thendried at 50 C under high vacuum for 24 h. The final product was obtained.The yield of donepezil-docusate, donepezil-ibuprofen,donepezil-oleate acid, donepezil-linoleate acid, donepezil-alpha linolenicacid and donepezil-docosahexaenoic acid were 96.54%, 91.35%,92.13%, 90.71%, 83.71% and 81.69%, respectively.
  • 69
  • [ 463-40-1 ]
  • [ 30334-71-5 ]
  • 1,2-dihexadecanoyl-3-((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
273 mg With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; 2.1.2.13. General procedure C: General procedure: Steglich esterification procedure. To asolution of diacylglycerol (1.0 equiv), N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDCI) (1.1-1.2 equiv.) and 4-(dimethylamino)pyridine (DMAP) (0.2-0.4 equiv.) in CH2Cl2 (2.5mL / mmol substrate), was added the corresponding unsaturated fattyacid (1.05-1.2 equiv.). After stirring overnight at room temperature,the resulting crude mixture was directly purified via columnchromatography.2.1.2.14. 1,2-Dihexadecanoyl-3-(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)-sn-glycerol, (R)-4a. (R)-4a was prepared using GeneralProcedure C, with (S)-3a (195 mg, 0.34 mmol), ALA (109 μL, 0.36mmol, 1.05 equiv.), EDCI (80.0 mg, 0.42 mmol, 1.2 equiv.) and DMAP(9.0 mg, 0.07 mmol, 0.2 equiv.) in CH2Cl2 (0.85 mL). Purification viacolumn chromatography (petroleum ether / EtOAc (5 %) gave (R)-4a(273 mg, 0.33 mmol, 97 %) as a white waxy solid (with a tint ofyellow); [α]D25 +0.02 (c 16.3, CHCl3); Rf 0.74 (petroleum ether / EtOAc (10%)); IR (thin film, νmax / cm-1) 3012, 2917, 2849, 1732; 1H NMR (400MHz, CDCl3) δH 5.50-5.25 (7H, m, 6 × =CH and CHOCO), 4.29 (2H,dd, J =12.0 and 4.0 Hz, 2×CH2OCO), 4.14 (2H, dd, J =12.0 and 6.0Hz, 2 × CH2’OCO), 2.81 (4H, app. t, J =6.5 Hz, 2 × =CCH2C=),2.37-2.26 (6H, m, 3× CH2COO), 2.14-2.01 (4H, m, =CCH2CH3 and=CCH2CH2), 1.67-1.55 (6H, m, 3 × CH2CH2COO), 1.39-1.18 (56H,m, 28×CH2), 0.98 (3H, t, J =7.5 Hz, =CCH2CH3), 0.88 (6H, t, J =6.5Hz, 2 × CH3); 13C NMR (101 MHz, CDCl3) δC 173.4, 173.3, 173.0,132.1, 130.4, 128.4, 128.3, 127.9, 127.3, 69.0, 62.3 (2), 34.4, 34.3,34.2, 32.1, 30.1, 30.0, 29.9, 29.8, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2,29.1, 29.0, 27.4, 25.8, 25.7, 25.1, 25.0, 24.9, 22.8, 20.7, 14.4, 14.3;HRMS (ESI+) calc. for C53H96O6Na [M + Na]+ 851.7099, found851.7094.
  • 70
  • [ 72-18-4 ]
  • [ 463-40-1 ]
  • C23H39NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at -10℃; for 0.333333h; Stage #2: L-valine With sodium hydroxide In tetrahydrofuran at -10 - 25℃; for 0.416667h; II. Synthesisof LA amino acid conjugates General procedure: To a stirred mixture of LA (0.88 mmol, 245.0 mg) and N(CH2CH3)3 (0.98 mmol, 0.14 mL) in THF (11 mL) at -10°C was added a solution of ethyl chloroformate (0.98 mmol, 0.098 mL), and the mixture was further stirred for 20 min. To this reaction mixture was added a solution of an amino acid (1.77 mmol) in 0.3 M NaOH (6.9 mL), and the reaction mixture was further stirred for 25 min at 25°C. The volatile component of the reaction mixture was removed under reduced pressure to give a crude oil. The resulting oil was washed with the following solutions: 0.1 M HCl (30 mL) and EtOAc (30 mL×3). The combined organic layers were dried over Na2SO4 and filtered. The volatile component of the solution was removed under reduced pressure to give a crude oil, and the resulting oil was subjected to silica gel column chromatography, whose conditions are described in each section for each synthesized compound.
  • 71
  • [ 56-86-0 ]
  • [ 463-40-1 ]
  • N-linolenoyl-L-glutamic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% Stage #1: (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at -10℃; for 0.333333h; Stage #2: L-glutamic acid With sodium hydroxide In tetrahydrofuran at -10 - 25℃; for 0.416667h; II. Synthesisof LA amino acid conjugates General procedure: To a stirred mixture of LA (0.88 mmol, 245.0 mg) and N(CH2CH3)3 (0.98 mmol, 0.14 mL) in THF (11 mL) at -10°C was added a solution of ethyl chloroformate (0.98 mmol, 0.098 mL), and the mixture was further stirred for 20 min. To this reaction mixture was added a solution of an amino acid (1.77 mmol) in 0.3 M NaOH (6.9 mL), and the reaction mixture was further stirred for 25 min at 25°C. The volatile component of the reaction mixture was removed under reduced pressure to give a crude oil. The resulting oil was washed with the following solutions: 0.1 M HCl (30 mL) and EtOAc (30 mL×3). The combined organic layers were dried over Na2SO4 and filtered. The volatile component of the solution was removed under reduced pressure to give a crude oil, and the resulting oil was subjected to silica gel column chromatography, whose conditions are described in each section for each synthesized compound.
  • 72
  • [ 56-85-9 ]
  • [ 463-40-1 ]
  • [ 157598-98-6 ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at -10℃; for 0.333333h; Stage #2: L-glutamine With sodium hydroxide In tetrahydrofuran at -10 - 25℃; for 0.416667h; II. Synthesisof LA amino acid conjugates General procedure: To a stirred mixture of LA (0.88 mmol, 245.0 mg) and N(CH2CH3)3 (0.98 mmol, 0.14 mL) in THF (11 mL) at -10°C was added a solution of ethyl chloroformate (0.98 mmol, 0.098 mL), and the mixture was further stirred for 20 min. To this reaction mixture was added a solution of an amino acid (1.77 mmol) in 0.3 M NaOH (6.9 mL), and the reaction mixture was further stirred for 25 min at 25°C. The volatile component of the reaction mixture was removed under reduced pressure to give a crude oil. The resulting oil was washed with the following solutions: 0.1 M HCl (30 mL) and EtOAc (30 mL×3). The combined organic layers were dried over Na2SO4 and filtered. The volatile component of the solution was removed under reduced pressure to give a crude oil, and the resulting oil was subjected to silica gel column chromatography, whose conditions are described in each section for each synthesized compound.
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[ 463-40-1 ]

Chemical Structure| 224568-13-2

A1267832[ 224568-13-2 ]

Linolenic-1-13C Acid

Reason: Stable Isotope