Home Cart 0 Sign in  

[ CAS No. 506-30-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 506-30-9
Chemical Structure| 506-30-9
Structure of 506-30-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 506-30-9 ]

Related Doc. of [ 506-30-9 ]

Alternatived Products of [ 506-30-9 ]

Product Details of [ 506-30-9 ]

CAS No. :506-30-9 MDL No. :MFCD00002755
Formula : C20H40O2 Boiling Point : -
Linear Structure Formula :- InChI Key :VKOBVWXKNCXXDE-UHFFFAOYSA-N
M.W : 312.53 Pubchem ID :10467
Synonyms :
Eicosanoic acid;C20:0 Fatty acid;Icosanoic Acid

Calculated chemistry of [ 506-30-9 ]

Physicochemical Properties

Num. heavy atoms : 22
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.95
Num. rotatable bonds : 18
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 100.03
TPSA : 37.3 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -1.61 cm/s

Lipophilicity

Log Po/w (iLOGP) : 4.56
Log Po/w (XLOGP3) : 9.29
Log Po/w (WLOGP) : 7.11
Log Po/w (MLOGP) : 5.13
Log Po/w (SILICOS-IT) : 7.01
Consensus Log Po/w : 6.62

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 1.0
Egan : 1.0
Muegge : 2.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -6.44
Solubility : 0.000113 mg/ml ; 0.000000361 mol/l
Class : Poorly soluble
Log S (Ali) : -9.97
Solubility : 0.0000000331 mg/ml ; 0.0000000001 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -6.91
Solubility : 0.0000384 mg/ml ; 0.000000123 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 2.77

Safety of [ 506-30-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 506-30-9 ]

* 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 [ 506-30-9 ]

[ 506-30-9 ] Synthesis Path-Downstream   1~70

  • 3
  • [ 4704-94-3 ]
  • [ 506-30-9 ]
  • [ 103650-86-8 ]
  • 4
  • [ 506-30-9 ]
  • [ 629-96-9 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride; diethyl ether
With lithium aluminium tetrahydride
92.3 %Chromat. With hydrogen In water at 220℃; for 24h; Autoclave; 2.3. Catalytic tests General procedure: Before the reaction test, the catalyst was activated in 10 vol%H2/Ar at 20 mL/min in 300 C for 2 h. Unless otherwise specified,1 mmol substrate, 0.05 g catalyst and 5 mL H2O were charged intoa stainless steel autoclave (NS10316L, Anhui Kemi MachineryTechnology Co., Ltd.). The reactor was sequentially purged withH2 for 5 times, pressured to 5.0 MPa H2, heated into 220 C, andkept at this temperature for 24 h. After the reaction, the reactionsystem was quickly cooled to room temperature in an ice-waterbath. After separation, the liquid products were analyzed by gaschromatography (Shimadzu GC-2010) with a flame ionizationdetector. 1,2-butanediol was used as an internal standard for theformation of diol, while 1-butanol was applied in the case of monohydricalcohol. The insoluble reactants and products in water were extracted by ethyl acetate, and analyzed with ethyl benzoate asinternal standard. Diethyl ether was used as extract in the conversion of stearic acid and palmitic acid. The gas products were analyzedby Agilent 7890A gas chromatograph equipped with a TCDdetector. All the products were identified by a Shimadzu GCMSQP2010gas chromatogram-mass spectrometer (GC-MS) andNMR spectroscopy (Bruker AV-III 400 MHz NMR spectrometer).
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 3h;

  • 5
  • [ 506-30-9 ]
  • [ 40140-09-8 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; In dichloromethane; for 4h;Reflux; Inert atmosphere; General procedure: Fatty acid 1 (2.9 mmol) was dissolved in anhydrous dichloromethane (0.1 M solution), and then thionyl chloride (3.0 equiv) was added under argon (Ar) atmosphere. The stirred suspension was heated to reflux for 4 h. Then the reaction mixture was cooled and poured onto crushed ice for 1 h. Piperazine (5.8 mmol) was added dropwise, and the reaction mixture was then allowed to warm up to room temperature and stirred for 2 h. NaOH solution (10%) was added (final pH 13), and the mixture was extracted with chloroform. The organic layer was washed with brine, dried over anhydrous MgSO4, and then concentrated in vacuo. The residue was purified by chromatography on silica gel with 5% MeOH/CHCl3 to afford the corresponding amides.
With thionyl chloride; In dichloromethane; at 60℃; for 4h;Inert atmosphere; General procedure: Fatty acid 1 (2.9 mmol) was dissolved in anhydrous dichloromethane (0.1 M solution), and thionyl chloride (3.0 equiv) was added under Argon (Ar) atmosphere. The stirred suspension was heated and refluxed for 4 h. The reaction mixture was cooled and poured onto crushed ice for 1 h, and 1-methylhomopiperazine (5.8 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. NaOH solution (10%) was added (final pH 13), and the mixture was extracted with chloroform. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel with 5% MeOH/CHCl3 to give the corresponding amides.
With thionyl chloride; In 1,2-dichloro-ethane;Reflux; To a solution (6 ml) of arachidic acid (1048 mg, 3.35 mmol) in 1 , 2-dichloroethane was added thionyl chloride (1.217 ml, 16.77 mmol), and the mixture was heated under reflux, and concentrated under reduced pressure to give acid chloride. To a solution (15 ml) of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin- 1-yl) butoxy] -l-hydroxymethyl-3, 4-dihydro-lH-quinolin-2-one (781 mg, 1.677 mmol) synthesized in the same manner as inExample 1 in dichloromethane were added pyridine (1.357 ml, 16.77 mmol) and the above-mentioned acid chloride, and the mixture was stirred at room temperature for 3 hr. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by moderate- pressure silica gel column chromatography (hexane : ethylacetate=l:0 to 1:1), and concentrated under reduced pressure. The residue was purified by basic silica gel columnchromatography (hexane : ethyl acetate=l:0 to 1:1), andconcentrated to dryness under reduced pressure to give the title compound (yield 856 mg, 67%) as a colorless oil.XH-NMR (CDC13) delta: 0.88 (t, J = 6.8 Hz, 3H) , 1.19-1.35 (m, 32H) , 1.57-1.68 (m, 2H) , 1.69-1.79 (m, 2H) , 1.80-1.90 (m, 2H) , 2.36 (t, J = 7.6 Hz, 2H) , 2.52 (t, J = 7.5 Hz, 2H) , 2.64-2.77 (m, 6H), 2.83-2.89 (m, 2H) , 3.14-3.25 (m, 4H) , 3.98 (t, J = 6.2 Hz, 2H) , 5.92 (brs, 2H) , 6.60 (dd, J = 2.3, 8.1 Hz, 1H) , 6.62 (d, J = 2.3 Hz, 1H), 6.87-6.92 (m, 1H) , 7.07 (d, J = 8.1 Hz, 1H) , 7.27 (dd, J = 7.8, 7.8 Hz, 1H) , 7.37-7.43 (m, 2H) , 7.55 (d, J = 8.1 Hz, 1H)
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 25℃; for 1.5h; Oxalyl chloride (2.67 ml, 0.0191 mol) was added drop-wise to a mixture of <strong>[506-30-9]Arachidic acid</strong> (6.0 g, 0.0211 mol) and DMF (4 drops) in dichloromethane (50 ml) at 0 C. After the addition was completed, the reaction mixture was stirred at 0 C. for 30 minutes and then stirred at 25 C. for 1 hour, the reaction mixture was partitioned between dichloromethane and water, and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine, then dried with sodium sulphate and concentrated in vacuo to provide the desired product (6.35 g, 100% yield) as a solid which was not purified any further.
With caprolactam; thionyl chloride; In ethanol; at -3℃; Accurately weigh 31.3 g (0.1 mol) of arachidic acid into a 250 mL three-necked flask,To the three-necked flask was added 50 mL of absolute ethanol and 2 g of the catalyst caprolactam,Then, 23.8 g (0.2 mol) of thaw chloride was distilled off,Dropping the speed of 1 drop / s,The acid chlorination reaction was carried out in an ice bath at -3 C,The reaction was monitored by thin layer chromatography (TLC)To be raw materials after the completion of the reaction of eicosanoids vacuum evaporation of excess of thionyl chloride and ethanol,To obtain 1-chloro-eicosanic acid;
With oxalyl dichloride; In dichloromethane; at 0 - 20℃; for 2h;Inert atmosphere; General procedure: A solution of oxalyl chloride in dry DCM (12 eq, 11.3 mL, 2M, 22.6 mmol) was added dropwise to a solution of the respective carboxylic acid (4 eq, 7.52 mmol) in dry DCM(20 mL) at 0C (ice bath) under nitrogen. The resulting mixture was stirred and allowed to reach room temperature over two hours. DCM was removed under vacuum and the acid chloride was dissolved in dry DMF (2mL) and cannulated into a solution of 3 (1.0eq, 0.5 g, 1.88 mmol) and dry pyridine (6.6 eq, 1 mL, 0.981 g, 12.40 mmol) in DMF(5 mL). The mixture was heated to 90C in an oil bath under a nitrogen atmosphere for two hours. After cooling the purple precipitate was filtered, washed with DMF(10 mL) and toluene (2 mL) and recrystallized from toluene.
With thionyl chloride; In 1,2-dichloro-ethane;Reflux; <strong>[506-30-9]Arachidic acid</strong> (1048 mg, 3.35 mmol)Thionyl chloride (1.217 ml, 16.77 mmol) was added to a 1,2-dichloroethane solution (6 ml)After heating under reflux, it was concentrated under reduced pressure to prepare an acid chloride.Was synthesized in the same manner as in Example 17- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy]-1-hydroxymethyl-3,4-dihydro-1 H-quinolin-2-one(781 mg, 1.677 mmol)In dichloromethane (15 ml)Pyridine (1.357 ml, 16.77 mmol),The above acid chloride was added and the mixture was stirred at room temperature for 3 hours.The organic layer was dried over sodium sulfate and concentrated under reduced pressure.The residue was purified by medium pressure silica gel column chromatography(Hexane: ethyl acetate = 1: 0 to 1: 1). Concentrate under reduced pressure,The residue was purified by basic silica gel column chromatography(Hexane: ethyl acetate = 1: 0 to 1: 1)Concentrated to dryness under reduced pressure to give the title compound as a colorless oil(Yield: 856 mg, 67%).
With thionyl chloride; for 3h;Reflux; 0.5g of arachidic acid was added to 5mL of SOCl2 and heated to reflux for 3h.The SOCl2 was distilled off under reduced pressure, and the obtained product was dissolved in 5 mL of dichloromethane.And slowly added dropwise to dissolve 1g of intermediate e and 0.1g of triethylamine15 mL of anhydrous DMF solution was reacted at room temperature for 12 h.After the reaction was completed, 20 mL of dichloromethane was added to dissolve.Then washed with 5% diluted hydrochloric acid, saturated sodium bicarbonate solution and saturated brine.The column was separated and purified, and the yield was 98%.
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h; General procedure: To a solution of the opportune carboxylic acid (0.46 mmol) in dry CH2Cl2 (2 mL), oxalyl chloride (58 muL, 0.69 mmol) in dry CH2Cl2 (0.5 mL) was added dropwise at 0 C under stirring. N,N-dimethylformamide (DMF, 1 drop) was added next. The reaction mixture was stirred at room temperature for 3 h and then concentrated under vacuum, giving crude acyl chloride. This residue was dissolved in dry CH2Cl2 (1 mL) and added dropwise to an ice-cold suspension of resorufin (50 mg, 0.23 mmol) and triethylamine (48 muL, 0.35 mmol) in dry CH2Cl2 (3 mL) and then stirred overnight at room temperature. After dilution with CH2Cl2 the salts residues were removed by filtration obtaining a brick-red solution; that was washed with 0.5 M HCl (2 mL) and saturated NaHCO3 (2.5 mL), dried on anhydrous Na2SO4 and concentrated to give the crude product that was purified with column chromatography on silica gel (Supplementary Table S1). Yields 62-92%.

Reference: [1]Monatshefte fur Chemie,1901,vol. 22,p. 418
    Monatshefte fuer Chemie,1906,vol. 27,p. 43
[2]Helvetica Chimica Acta,1964,vol. 47,p. 526 - 544
[3]Journal of the American Chemical Society,1984,vol. 106,p. 7033 - 7037
[4]Journal of the American Chemical Society,1984,vol. 106,p. 4531 - 4536
[5]Journal of Physical Chemistry,1993,vol. 97,p. 12848 - 12857
[6]Archiv der Pharmazie,2007,vol. 340,p. 483 - 490
[7]Synthesis,2008,p. 3663 - 3669
[8]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 5103 - 5113
[9]Journal of Lipid Research,2010,vol. 51,p. 42 - 52
[10]European Journal of Medicinal Chemistry,2011,vol. 46,p. 2861 - 2866
[11]Journal of Natural Products,2011,vol. 74,p. 1364 - 1369
[12]Analytical Chemistry,2012,vol. 84,p. 2388 - 2394
[13]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 788 - 794
[14]Patent: WO2013/35892,2013,A1 .Location in patent: Paragraph 0366-0368
[15]Crystal Growth and Design,2014,vol. 14,p. 4944 - 4954
[16]Patent: US2016/9713,2016,A1 .Location in patent: Paragraph 0118
[17]Chemistry and Physics of Lipids,2016,vol. 201,p. 1 - 10
[18]Patent: CN106167506,2016,A .Location in patent: Paragraph 0042
[19]Molecular Crystals and Liquid Crystals,2018,vol. 665,p. 82 - 90
[20]Patent: JP2018/203793,2018,A .Location in patent: Paragraph 0359; 0360; 0361
[21]Patent: CN109503693,2019,A .Location in patent: Paragraph 0055; 0072-0075
[22]Molecules,2019,vol. 24
[23]Angewandte Chemie - International Edition,2020,vol. 59,p. 3307 - 3314
    Angew. Chem.,2020,vol. 132,p. 3333 - 3340,8
[24]Patent: CN110981933,2020,A .Location in patent: Paragraph 0076; 0092-0094
  • 6
  • [ 6066-82-6 ]
  • [ 506-30-9 ]
  • [ 69888-87-5 ]
YieldReaction ConditionsOperation in experiment
With dicyclohexyl-carbodiimide; In DMF (N,N-dimethyl-formamide); dichloromethane; at -5 - 20℃; for 16h; A. Preparation of eicosanoic Acid N-hydroxysuccinimide Ester Intermediate eicosanoic acid (5.0 mmol) was dissolved in 40 ML of dichloromethane and 10 ML of N,N-dimethylformamide. 1-N-Hydroxysuccinimide (5.0 mmol) and N,N-dicyclohexyl-carbodiimide (5.0 mmol 10.0 ML, of 0.5 M solution) was added at -5 C. and the solution allowed to warm up to room temperature and the reaction mixture stirred at room temperature for 16 hr.. dicyclohexyl urea precipitate was filtered off.. The filtrate was concentrated and the N-hydroxysuccinimide ester derivative purified by crystallization from dichloromethane-n-hexane solution.
  • 7
  • [ 51-28-5 ]
  • [ 506-30-9 ]
  • [ 168907-26-4 ]
  • 8
  • [ 506-30-9 ]
  • [ 1849-36-1 ]
  • [ 168907-23-1 ]
  • 10
  • [ 506-30-9 ]
  • [ 440-60-8 ]
  • Eicosanoic acid pentafluorobenzyl ester [ No CAS ]
  • 11
  • [ 506-30-9 ]
  • [ 100-79-8 ]
  • [ 57156-96-4 ]
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.
  • 12
  • 15-hydroxyimino-tetratriacontanoic acid [ No CAS ]
  • [ 7664-93-9 ]
  • [ 1460-18-0 ]
  • [ 14130-05-3 ]
  • [ 17437-20-6 ]
  • [ 506-30-9 ]
  • 13
  • [ 103799-79-7 ]
  • [ 7664-93-9 ]
  • [ 14130-05-3 ]
  • [ 13108-19-5 ]
  • [ 1852-04-6 ]
  • [ 506-30-9 ]
  • 14
  • [ 506-30-9 ]
  • [ 154383-61-6 ]
  • (S)-2-(4-Icosanoylamino-benzoylamino)-4-methylsulfanyl-butyric acid methyl ester [ No CAS ]
  • 15
  • [ 50908-04-8 ]
  • [ 506-30-9 ]
  • [ 404918-73-6 ]
  • 16
  • [ 3590-93-0 ]
  • [ 506-30-9 ]
  • Icosanoic acid 2,6-dimethoxy-4-((5R,5aR,8aR)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester [ No CAS ]
  • 17
  • [ 506-30-9 ]
  • [ 136586-99-7 ]
  • di-tert-butyl 4-(2-(tert-butoxycarbonyl)ethyl)-4-(1-oxoicosylamino)heptanedioate [ No CAS ]
  • 18
  • [ 506-30-9 ]
  • [ 51360-63-5 ]
YieldReaction ConditionsOperation in experiment
98% With titanium(IV) isopropylate; ammonia; at 165℃; for 7.5h; General procedure: According to the embodiment of the present invention described above, stearic acid amide, which is a kind of carboxylic acid amide compound, was prepared in Example 1 as follows. First, the carboxylic acid injector 250 injects 1000 g of stearic acid into the heater 100, and the heater 100 heats 1000 g of stearic acid to 120 C. Subsequently, when stearic acid is injected into the first reaction tank 210, the first catalyst injector 261 injects 10 g of tetraisopropyl titanium, which is a metal catalyst, into the first reaction tank 210, Was heated by the heater attached to the first reaction tank 210. When 150 g of stearic acid was charged into the first reaction tank 210, the first ammonia injector 281 started to feed the ammonia gas through the ammonia pipe 283 at a rate of 100 L / hr. When 500 g of stearic acid was charged into the first reaction tank 210, the introduction of stearic acid into the first reaction tank 210 was stopped. The propeller in the first reaction tank 210 was mixed with stearic acid and ammonia while maintaining the reaction temperature at 165 C in the first reaction tank 210.Next, when the supply of the stearic acid to the first reaction tank 210 is stopped, the 500 g of stearic acid remaining in the heater 100 through the valve is changed to be supplied to the second reaction tank 220. When stearic acid is injected into the second reaction tank 220, the second catalyst injector 262 injects 10 g of tetraisopropyl titanium as a metal catalyst into the second reaction tank 220 and starts heating the second reaction tank 220 . When 150 g of stearic acid was charged into the second reaction tank 220, the second ammonia feeder 282 started to feed the ammonia gas through the ammonia pipe 283 at a rate of 100 L / hr. When all 500 g of stearic acid was fed to the second reaction tank, the addition of stearic acid to the second reaction tank was stopped. The propeller in the second reaction tank 220 was mixed with stearic acid and ammonia while maintaining the reaction temperature of 165 C in the second reaction tank 220.In Examples 2 to 10, other carboxylic acid amide compounds were prepared in the same manner as in Example 1, except that stearic acid was used instead of stearic acid and other carboxylic acids as shown in the following Table 1 as "acid".
  • 20
  • [ 8001-23-8 ]
  • [ 373-49-9 ]
  • [ 112-80-1 ]
  • [ 112-79-8 ]
  • [ 544-70-7 ]
  • [ 544-70-7 ]
  • [ 7307-45-1 ]
  • [ 1072-36-2 ]
  • [ 60-33-3 ]
  • [ 60-33-3 ]
  • [ 29204-02-2 ]
  • [ 506-30-9 ]
  • [ 112-85-6 ]
  • [ 544-63-8 ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
  • [ 117624-52-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; ethanol; water; at 150 - 215℃; under 7500.75 - 24002.4 Torr; for 0 - 6h;Product distribution / selectivity; Example 1; A comparison was carried out between reactions carried out in 96% ethanol (according to the invention), and 99.9% ethanol (dry ethanol, comparative example). Both reactions were catalysed by sodium hydroxide, which was used in the form of dry pellets. Safflower oil was used as source for linoleic acid. The sample removed at t=0 hr is the first sample taken when the desired temperature was reached. The reaction mixture was analysed by the fatty acid methyl ester (FAME) method using gas chromatography. The results for the process using 96% ethanol are set out in the following table: The results for the process using 99.9% ethanol are set out in the following table When 96% ethanol was used with addition of extra water, 96.6% of C18:2c was converted in 6 hours. Using dry ethanol gave a conversion of 99.5% in 6 hours. However, the reaction mixture with the lower water content produced higher amounts of the conjugated trans, tans isomer, was very viscous and difficult to stir and to remove samples.; Example 4; COMPARATIVE EXAMPLE; A comparative example was carried out to show the formation of trans, trans isomers at temperatures outside the claimed range. Saffower oil (200 g), caustic soda (45 g) and 95-97% ethyl alcohol (450 ml) were heated under a pressure of 30-32 bar at 210-215 C. for 4 hours. Samples of the reaction mixture were taken at the start of the reaction and at 2 and 4 hours. The reaction mixture was analysed by the fatty acid methyl ester (FAME) method using gas chromatography. The results for the trans, trans conjugated isomer of CLA were as follows:; Example 1; A comparison was carried out between reactions carried out in 96% ethanol (according to the invention), and 99.9% ethanol (dry ethanol, comparative example). Both reactions were catalysed by sodium hydroxide, which was used in the form of dry pellets. Safflower oil was used as source for linoleic acid. The sample removed at t=0 hr is the first sample taken when the desired temperature was reached. The reaction mixture was analysed by the fatty acid methyl ester (FAME) method using gas chromatography. The results for the process using 96% ethanol are set out in the following table: The results for the process using 99.9% ethanol are set out in the following table When 96% ethanol was used with addition of extra water, 96.6% of C18:2c was converted in 6 hours. Using dry ethanol gave a conversion of 99.5% in 6 hours. However, the reaction mixture with the lower water content produced higher amounts of the conjugated trans, tans isomer, was very viscous and difficult to stir and to remove samples.
With potassium hydroxide; ethanol; water; at 150℃; under 7500.75 - 9000.9 Torr; for 0 - 6h;Product distribution / selectivity; Example 2; An experiment was carried out to compare processes carried out using ethanol (EtOH) (according to the invention) and propylene glycol (MPG) (comparative example). These reactions were catalysed by potassium hydroxide. Safflower oil was used as source for linoleic acid. The water in the system is from the potassium hydroxide used. Reaction Conditions: The results of FAME analysis of the reaction in ethanol were as follows: The results of FAME analysis of the reaction in propylene glycol were as follows: When 96% ethanol was used as solvent, 99.5% of C18:2c was converted in 2 hours. Using propylene glycol gave a conversion of 90.7% in 2 hours.; Example 3; A series of five experiments was carried out using safflower oil (300 g)>potassium hydroxide pellets and 96% ethanol (250 ml) as the solvent. The amount of potassium hydroxide was varied (72.6 g, 77.5 g, 85.3 g, 103 g and 120.6 g). Since the pellets used contain about 15% water, the water content also varied as a result of varying the amount of potassium hydroxide. The amount of water used in the examples was 10.9%, 11.3%, 11.9%, 13.3% and 14.6%. A measurement of the conversion of linoleic acid showed that the rate of reaction increased with increasing water content, at these levels of water content.
With potassium hydroxide; water; In propylene glycol; at 150℃; under 7500.75 - 9000.9 Torr; for 0 - 6h;Product distribution / selectivity; Example 2; An experiment was carried out to compare processes carried out using ethanol (EtOH) (according to the invention) and propylene glycol (MPG) (comparative example). These reactions were catalysed by potassium hydroxide. Safflower oil was used as source for linoleic acid. The water in the system is from the potassium hydroxide used. Reaction Conditions: The results of FAME analysis of the reaction in ethanol were as follows: The results of FAME analysis of the reaction in propylene glycol were as follows: When 96% ethanol was used as solvent, 99.5% of C18:2c was converted in 2 hours. Using propylene glycol gave a conversion of 90.7% in 2 hours.
  • 21
  • Grape seed oil [ No CAS ]
  • conjugated linoleic acids; mixture of [ No CAS ]
  • [ 506-30-9 ]
  • [ 544-63-8 ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
YieldReaction ConditionsOperation in experiment
PREPARATIVE EXAMPLE 1; Synthesis of CLA by Alcaline Isomerization of Grape Seed Oil in Glycerol (The following synthesis makes the object of a co-pending application); 1 kg glycerol, 235 g potassium hydroxide (KOH) and 1000 g of grape seed oil were added into a 4-neck round bottom flask (5000 ml) equipped with a mechanical stirrer, a thermometer, a reflux condenser, and a nitrogen inlet, the nitrogen being introduced in first run through two oxygen traps.Nitrogen was bubbled into the reaction mixture for 20 min and the temperature was then raised to 90-100 C., and kept under mechanical stirring for about 20 minutes to convert the trigliceride in the corresponding potassium salts. The double phase system disappears to form a glyceric soap suspension, then heated at 230 C. under inert atmosphere and stirred for 4 hours.The reaction mixture was cooled to about 100 C., and the stirring stopped as the reaction mixture tend to reach very high viscosity during cooling. 2 l of water was then slowly added, and the mixture kept at 95 C. for 2 hour. This operation becomes necessary because of the neglegible presence of water and high content of glycerol causing fatty acids to be present as mono- and diglyceride from 5% to 10% by weight of the total lipid content. As partial glyceride esters tend to form W/O emulsion, the water addition and re-heating provides full saponification of the residual esterified fatty acid.The mixture was transferred into a becker, then cooled to room temperature and 50% w/v sulfuric acid was added to the mixture which was stirred for 1 hour until the pH stabilized at about 3.The acidulated oil phase formed a lower hydroglyceric layer and an upper fatty acid oil layer containing CLA, which was separated by decantating. Noteworthy, in industrial operation the separation could be carried out by centrifugation.The CLA was washed with water and finally it was made anhydrous with sodium sulphate and filtered, then it is stored in a dark bottle at 4 C. until time of use. Total yield about 770 g af an amber oil, whose GC-analysis is shown in Table 1; The composition of CLA appears to be a complex mixture, i.e. 9c, 11t- and 8c, 10t-octadecadienoic acids at 30.90%, 11c, 13t-10t, 12c-octadecadienoic acids at 32.05%, 11t, 13c-8c, 10c-9c, 11c-octadecadienoic acid at 1.55%, 10c, 12c-11c, 13c-11t, 13t, 9t, 11t-10t, 12t-8t,10t-octadecadienoic acids making the remaining part.
  • 22
  • [ 506-30-9 ]
  • [ 725693-27-6 ]
  • [ 725693-31-2 ]
YieldReaction ConditionsOperation in experiment
15% With dmap; dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; for 72h; <strong>[506-30-9]Arachidic acid</strong> (611 mg, 4 eq, 1.95 mmol), DCC (402 mg, 4 eq, 1.95 mmol) and DMAP (238 mg, 4 eq, 1.95 mmol), were added to uridine phosphocholine (200 mg, 0.49 mmol) in 20 mL of anhydrous DMF. After 72 hours at room temperature, the DMF was evaporated and the residual solid is dissolved in 20 mL of methylene chloride. DCU was removed by filtration and solvent evaporated. The crude material was purified by exclusion chromatography (LH 20, DCM/MeOH 5/5). 73 mg of the product were isolated. (Yield: 15%). The characterization data were consistent with the chemical structure.
  • 25
  • [ 506-30-9 ]
  • [ 109786-74-5 ]
  • (R)-1,2-di-eicosyloxycarbonyl-3-(p-methoxybenzyl)-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 22h; p-Methoxybenzyl glycerol (212 mg, 1 mmol), eicosanoic acid (781 mg, 2.5 mmol) and dimethylaminopyridine (24 mg, 0.2 mmol) were dissolved in dry dichloromethane (50 ml) and cooled to 0C. Dicyclohexylcarbodiimide (516 mg, 2.5 mmol) was dissolved in 10 ml dry dichloromethane and was added slowly to the stirred reaction mixture. The reaction mixture was allowed to warm up to room temperature and stirred for 22 h. The solvent was removed under reduced pressure und the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate: 6: 1) to give (R)-1,2-di-eicosyloxycarbonyl-3-(p- methoxyberizyl)-sn-glycerol (724 mg, 90%).
  • 26
  • [ 506-30-9 ]
  • [ 154372-20-0 ]
  • [ 867062-60-0 ]
YieldReaction ConditionsOperation in experiment
98% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 24h; Esterification (inositols and glycerols) To a solution of alcohol (1.0 eq) in CH2Cl2 (5 mL) was added DCC (1.4 eq), DMAP (0.66 eq) and the corresponding acid (1.4 eq) and stirred under argon atmosphere for 24 h at room temperature. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography (silica, petroleum ether/EtOAc) to afford the product.Esterification was performed as described in the general procedure to obtain compound 10 (583 mg, 98 %) as a waxy solid.
  • 27
  • [ 908094-01-9 ]
  • [ 506-30-9 ]
  • [ 1120-28-1 ]
YieldReaction ConditionsOperation in experiment
In Petroleum ether Acidic conditions;
  • 28
  • [ 506-30-9 ]
  • [ 155021-56-0 ]
  • [ 1042940-11-3 ]
  • 29
  • [ 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).
  • 30
  • [ 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.
  • 31
  • [ 67-56-1 ]
  • [ 112-79-8 ]
  • 9,12-octadecadienoic acid [ No CAS ]
  • [ 373-49-9 ]
  • [ 506-30-9 ]
  • [ 57-10-3 ]
  • [ 57-11-4 ]
  • [ 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 ]
  • [ 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 at 50 - 53℃; for 20 - 72h; Neat (no solvent); Stage #2: With ethyl vinyl ether Stage #3: methanol 2; 12; 13 Synthesis of diacids (19a-19d) from tall acids (TFA): TFA (16d, (Table 3) 2.5 g, 8.9 mmol) and were metathesized with catalyst 2 (7.5 mg, 8.8 mmol) under conditions used for SFA. At the end of the reaction (12 h) only a small amount of diacid precipitate was observed. The crude reaction mixture was isolated and methylated as above. The GC chromatogram for this methyl ester product is shown in FIG. 6C. The crude ester product (1 g) was fractionally separated by silica gel chromatography using hexane:ethyl acetate (95:5 v/v) as the eluant into a hydrocarbon fraction (17a-17c, 126 mg); an unsaturated fatty methyl ester fraction (18a-18g, 460 mg); and a dimethyl ester fraction (19a-19d, 380 mg, 70% yield). The diester fraction (19a-19d) was analyzed by GC/MS: (retention time=27.5-34 min FIG. 5c) and showed [M]+ ions of m/z 340 (19a); m/z 354 (19b); m/z 368 (19c); and m/z 382 (19d).
  • 32
  • 5''-amino-1,3,2',6',2''',6'''-hexa-N-(tert-butoxycarbonyl)-5''-deoxy-neomycin [ No CAS ]
  • [ 506-30-9 ]
  • [ 1067241-24-0 ]
  • 33
  • [ 506-30-9 ]
  • [ 629-92-5 ]
YieldReaction ConditionsOperation in experiment
35% With 2,4,6-trimethyl-pyridine; ammonium peroxydisulfate In dimethylsulfoxide-d6 at 60℃; for 2h; Sealed tube; Inert atmosphere;
With 1% Pd/C Selcat Q6 In dodecane at 300℃; for 2.5h; Inert atmosphere;
With photodecarboxylase from Chlorella variabilis NC64A In dimethyl sulfoxide at 37℃; for 14h; Irradiation; Sealed tube; Enzymatic reaction;
  • 35
  • [ 23214-92-8 ]
  • [ 506-30-9 ]
  • [ 1310544-49-0 ]
YieldReaction ConditionsOperation in experiment
88.2% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Inert atmosphere; General procedure: Fatty acyl amide derivatives of doxorubicin (2-10) were synthesized by coupling reaction of doxorubicin and the fatty acids in presence of HBTU. All derivatives were synthesized using a similar procedure. As a representative example the synthesis of tetradecanoyl amide derivative is described here. Doxorubicin (50 mg, 0.09 mmol) was suspended in dry DCM (10 mL). Myristic acid (20.9 mg, 0.09 mmol) and HBTU (115 mg, 0.30 mmol) in dry DCM (20 mL) were added slowly to the reaction mixture. Next, DIPEA (100 mg, 0.77 mmol) was added to the reaction mixture at room temperature. The mixture was stirred for 3 h under nitrogen atmosphere. After completion of the reaction (TLC product Rf = 0.8, doxorubicin Rf = 0.1 in DCM/Methanol (8:2 v/v)), water (50 mL) was added to the mixture and the crude product was extracted with DCM (3 × 40 mL). After removal of DCM under reduced pressure, the crude product was purified by column chromatography over silica gel using DCM/methanol (0-20%) as the eluents to afford product (63 mg, 90.8%). The product was further purified on a reverse phase HPLC using C18 column and gradient methanol/water as mobile phase as described above.
  • 36
  • [ 49715-04-0 ]
  • [ 506-30-9 ]
  • [ 77878-05-8 ]
YieldReaction ConditionsOperation in experiment
71% With tetra(n-butyl)ammonium hydrogensulfate; sodium carbonate; In dichloromethane; at 25℃; Example 10; 1-((eicosanoyloxy)methyl)-1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium iodide (Compound 10)To a suspension of arachidic acid (8 g, 25.6 mmol) in water (80 mL) was added Na2CO3 (10.9 g, 102.4 mmol). After 20 minutes, the reaction was cooled to 0 C. and nBu4NHSO4 (1.74 g, 5.12 mmol), dichloromethane (160 mL) and chloromethyl chlorosulfate (3.4 mL, 33.3 mmol) were added. The reaction was allowed to warm to 25 C. and stirred overnight. The reaction mixture was separated and the aqueous extracted with dichloromethane (2×200 mL). The combined organics were dried (MgSO4) and concentrated in vacuo. The product was purified by column chromatography eluting with heptane to 10% dichloromethane/heptane to give the product (6.54 g, 71%).
  • 37
  • [ 506-30-9 ]
  • [ 82203-82-5 ]
  • [ 1309369-50-3 ]
  • 38
  • [ 506-30-9 ]
  • [ 102522-47-4 ]
  • [ 1279697-36-7 ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: Arachidic acid With dicyclohexyl-carbodiimide In dichloromethane for 0.5h; Stage #2: 6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecan-6-amine With dmap In dichloromethane for 2h;
  • 39
  • [ 687-64-9 ]
  • [ 506-30-9 ]
  • C47H92N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; for 16h; To a stirred solution of 01-34-2 (5 g, 0.0312 mol) in DMF (100 mL) at RT was added slowly DIPEA (32 mL, 0.1872 mol), linear fatty acid 01-34-1 (29.2 g, 0.0936 mol), and HATU (41.5 g, 0.1092 mol). The resulting mixture was stirred at 50 C. After 16 h, the reaction mixture was quenched with ice water, the solids isolated by filtration, and then the solids dried under vacuum. Purification of the solids by trituration with THF afforded 01-34-3 as an off-white solid (10 g, 43%).
  • 40
  • [ 506-30-9 ]
  • [ 99-98-9 ]
  • [ 1421060-62-9 ]
YieldReaction ConditionsOperation in experiment
38.4% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 8h;Inert atmosphere; General procedure: Carboxylic acid 1 (2.9 mmol) was dissolved in anhydrous dichloromethane (0.2 M) at room temperature under an Ar atmosphere. N,N-dimethyl-1,4-phenylenediamine (4.3 mmol), EDC (4.3 mmol) and DMAP (0.9 mmol) were added, and the mixture was stirred for 8 h at room temperature. Saturated NH4Cl solution was added, and the mixture was extracted with dichloromethane (3×). The organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel with 5% MeOH/CH2Cl2 to resolve amides.
  • 41
  • [ 4224-70-8 ]
  • n-tetradecylmagnesium chloride [ No CAS ]
  • [ 506-30-9 ]
  • 42
  • [ 506-30-9 ]
  • [ 127-06-0 ]
  • [ 1544620-07-6 ]
YieldReaction ConditionsOperation in experiment
99% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; To a solution of eicosanoic acid (710mg, 2.27mmol), DMAP (20mg, 0.16mmol) and EDAC (463mg, 2.42mmol) in dried dichloromethane (10ml), acetone oxime (193mg, 2.64mmol) was added and the resulting solution was stirred overnight at rt. The reaction solution was passed through a short silica gel column with ethyl acetate/petroleum ether (60:40) as an eluent, affording the product as white crystalline material after evaporation of the solvents and recrystallization from petroleum ether (826mg, 2.25mmol) in 99% yield. Mp=60.6-62.0C. 1H NMR delta 2.39 (t, J=7.6Hz, 2H, CH2COO), 2.04 (s, 3H, N=C(CH3)2), 2.00 (s, 3H, N=C(CH3)2), 1.68 (quin, J=7.6Hz, 2H, CH2CH2COO), 1.38-1.18 (m, 32H, CH2), and 0.87 (t, J=6.8Hz, 3H, -CH3)ppm. 13C delta 171.2 (C=O), 163.6 (C=N), 33.0, 31.9, 29.7 (10), 29.6, 29.3, 29.2, 29.1, 25.0, 22.7, 22.0, 16.9 and 14.1ppm. IR numax 2917 (vs, C-H), 2848 (vs, C-H) and 1757 (vs, C=O)cm-1. HRMS (ESI): calcd for C23H45NO2Na+ m/z 390.3343; found 390.3358amu.
  • 43
  • [ 506-30-9 ]
  • [ 1376134-24-5 ]
  • C38H53NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; acetonitrile; at 90℃; for 0.583333h; General procedure: 150 muL standard fatty acid mixtures, 200 muL BCETS and 100 muL DMF were added orderly to a 2 mL vial containing 15 mg K2CO3. The vial was sealed and allowed to react in a water bath at 90 C for 35 min. 100muL supernatant obtained above was removed to dry under a stream of nitrogen gas in a 2 mL vial and then 15 mg K2CO3, 200 muL BCETS and 100 muL DMF were added orderly into the vial. The vial was sealed and allowed to react in a water bath at 90 C for 35 min. After the reaction was completed, the mixture was cooled to room temperature. The derivatization solution was syringe filtered using a 0.22 mm nylon filter and injected directly into the chromatograph column. The injected volume was 10 muL. The derivatization procedure of fatty acids with BCETS was shown in Fig. 2.
  • 44
  • [ 506-30-9 ]
  • [ 4136-95-2 ]
  • [ 185230-64-2 ]
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.
  • 45
  • methyl (24R,25S)-dihydroxy-26-O-nonadecylcarbonyloxy-3,4-secocycloarta-4(28)-en-3-oate [ No CAS ]
  • [ 506-30-9 ]
  • 24R,25S,26-trihydroxy-3,4-secocycloarta-4(28)-en-3-oic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
3 mg; 6 mg With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 50℃; for 3h; To a stirred solution of 1a (10.4 mg, 0.013 mmol) in a 1:2 mixture of THF-H2O (3 mL),LiOH.H2O (1.2 mg, 0.029 mmol) was added at room temperature. Then, the reaction mixturewas heated at 508C for 3 h (TLC monitoring, with cyclohexane-EtOAc (2:1) as eluent), andthen concentrated in vacuo to dryness. The residue was taken up in 3mL of AcOH-H2O(3:1) and the resulting solution was extracted twice with 5mL of CH2Cl2. The solvent wasevaporated under reduced pressure and the oily residue was partitioned between cyclohexane(3 mL) and a 3:1 mixture of MeOH-H2O (3 mL). Both fractions were concentrated underreduced pressure to dryness in order to obtain as colourless oils, eicosanoic acid (arachidicacid, 3 mg) and 1b (6 mg), respectively. The identification of the fatty acid was confirmed bymass spectrometry analysis (ESI-MS: m/z 311 [M 2 H]2, 623 [2M 2 H]2 (Calcd forC20H40O2, 312)).
  • 46
  • [ 79-20-9 ]
  • [ 506-30-9 ]
  • [ 1120-28-1 ]
YieldReaction ConditionsOperation in experiment
With sodium methylate In hexane Heating;
  • 47
  • [ 506-30-9 ]
  • [ 62-31-7 ]
  • [ 565186-20-1 ]
YieldReaction ConditionsOperation in experiment
32.5% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 0 - 20℃; for 0.5h;Inert atmosphere; General procedure: Dopamine hydrochloride (60.7 mg, 0.32 mmol) and palmitoleic acid (91.0 muL, 0.32 mmol) were mixed in dry CH2Cl2(1 mL) under an Ar atmosphere, and triethylamine (133 muL, 0.96 mmol) was added at 0C. PPACA (50% in ethyl acetate, 200 muL, 0.32 mmol) was slowly added over 30 min at the same temperature, and the reaction mixture was stirred at room temperature overnight. The mixture was worked up followed by evaporation, and the residue was purified by column chromatography (eluent; EtOAc-hexane=1 : 1-4 : 1) to give N-palmitoleoyl dopamine (22.6 mg, 18.1%) as a colorless oil.
  • 48
  • [ 608-07-1 ]
  • [ 506-30-9 ]
  • [ 1192062-13-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; General procedure: <strong>[506-30-9]Arachidic acid</strong> (0.11 mmol, 0.034 g) is mixed with HATU (0.11 mmol, 0.042 g) and triethylamine (0.5 mL, co-solvent) in DMF (2 mL, anhydrous). The reaction mixture is stirred for 30 minutes, and the appropriately substituted compound (0.1 mmol) is added. The reaction mixture is stirred at room temperature for about 4 to about 16 hrs (monitored by HPLC). Upon completion NH4Cl (10 mL, aq., saturated) is added and the solid is collected by filtration, is washed with water (10 mL×2), NaHCO3 (10 mL×2, aq., is saturated) and is washed finally by acetonitrile (2 mL). The desired product is dried under the vacuum.The desired compound is prepared substantially as described above in Example 8 except that 5-methoxy-tryptamine is used as the starting material. ES-MS: mass calculated for Chemical Formula: C31H52N2O2 484.8 (M+).
  • 49
  • [ 50-67-9 ]
  • [ 506-30-9 ]
  • [ 21249-34-3 ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; triethylamine; In N,N-dimethyl-formamide; at 20℃; <strong>[506-30-9]Arachidic acid</strong> (9.38 g, 30 mmol) was mixed with the appropriate amounts (30-45 mmol) of a coupling reagent, and if needed, an additional activating agent (10-45 mmol) (e.g., HOBt, heterocyclic base, heterocyclic acid) and/or organic base (10-60 mmol) (e.g., triethylamine, DIEA, pyridine, DABCO, non-nucleophilic basic nitrogen containing molecule) in an appropriate solvent (e.g., DMF, THF, dioxane, DCM, DCE, glyme, diglyme). The reaction mixture was stirred for 0.5-6 hrs, then serotonin (it's salt, free base or appropriately protected form) was added (either neat or premixed with solvent and/or organic base). The reaction mixture was stirred at room temperature for about 4 to about 16 hrs (monitored by HPLC). Upon completion the excess of the organic solvent was removed and the residual oil was treated with aqueous acid (0.1-3 N HCl, NH4Cl (aq., saturated), 0.1-1N H2SO4, etc.). N-(2-5-hydroxy-1H-indol-3-yl)ethyl)propionamide was collected by filtration as amorphous solid, washed with water (4×250 mL) and acetonitrile (100 mL). The product was dried under the vacuum and re-crystallized from hot organic solvent (ethanol, methanol, isopropanol, acetonitrile, EtOAc, THF, etc.) to yield 12.43 g (88%) of N-(2-5-hydroxy-1H-indol-3-yl)ethyl)propionamide as an off-white amorphous solid.
  • 50
  • [ 506-30-9 ]
  • [ 63-91-2 ]
  • N-eicosanoyl-L-phenylalanine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Method B: To a solution of fatty acid (1 eq.) in DCM was added oxalyl chloride (1.2 eq.) and one drop of DMF at 0C. Then, the mixture was stirred at room temperature for 2 hours. The mixture was concentrated and dissolved in DCM and added to a suspension of amino acid (1.5 eq.) and DIPEA (2 eq.). The reaction mixture was stirred at room temperature overnight before being acidified by HC1 (1.0 M) to pH 4.0. The resulting mixture was extracted with DCM, washed with brine, and dried over anhydrous Na2S04. Then, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel to give the desired amide. Icosanoyl-L-phenylalanine, Method B. White solid. 1H MR (400 MHz, DMSO-d6) delta 0.86 (t, J = 5.0 Hz, 3H), 1.09-1.31 (m, 32H), 1.33-1.40 (m, 2H), 2.02 (t, J = 7.3 Hz, 2H), 2.83 (dd, J = 10.2, 13.8 Hz, 1H), 3.05 (dd, J = 5.3, 14.2 Hz, 1H), 4.38-4.44 (m, 1H), 7.17-7.28 (m, 5H), 8.08 (d, J= 8.0 Hz, 1H), 12.97 (brs, 1H) HRMS (ESI) m/z calcd for C29H50NO3 [M+H]+ 460.3785, found: 460.3796
  • 51
  • [ 506-30-9 ]
  • [ 147-85-3 ]
  • C25H47NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Dicyclohexylcarbodiimide (DCC) (10.45 g, 50.6 mmol) and N-hydroxysuccinimide (NHS) (5.83 g, 50.6 mmol) are added successively to an arachidonic acid solution (15.51 g, 49.63 mmol) in THF (500 mL) at 0 C. After 17 h of stirring at room temperature, the medium is cooled to 0 C. for 20 min, filtered through a sintered filter. L-proline (6 g, 52.11 mmol), DIPEA (60.5 mL) and water (50 mL) are added to the filtrate. After 48 h of stirring at room temperature, the mixture is treated with a 1N aqueous HCl solution to pH 1, and the resulting solid is filtered through a sintered filter, washed with water until the pH of the mother liquors is neutral, then dried under a vacuum to yield a yellowish solid. After purification by chromatography on silica gel (cyclohexane, ethyl acetate), a white solid is obtained. Yield: 10.96 g (54%). 1H NMR (CDCl3, ppm): 0.88 (3H); 1.28 (34H); 1.66 (2H); 1.95-2.15 (2H); 2.34 (2H); 2.45 (1H); 3.47 (1H); 3.56 (1H); 4.60 (1H). LC/MS (ESI): 410.4; (calculated ([M+H]+): 410.6).
  • 52
  • [ 167308-64-7 ]
  • [ 506-30-9 ]
  • (R)-S-icosanoyl-N-pantothenoylcysteamine acetonide [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; General procedure: To a stirred solution of an acid in dry DCM, p-dimethylaminopyridine (DMAP) and 8 were added. N-(3-Dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (EDC·HCl) was added at 0 C, the solution was stirred for 5 minutes at 0 C and overnight at room temperature [12]. 1N HCl was added to the reaction mixture followed by extraction with DCM three times. The combined organic phases were washed with sat. NaHCO3 sol. and brine, dried with MgSO4, filtered and concentrated to give an oil.
  • 53
  • [ 506-30-9 ]
  • C125H166N17O20PolS3 [ No CAS ]
  • C145H204N17O21PolS3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In 1-methyl-pyrrolidin-2-one; at 50℃; for 0.5h; The title compound was prepared according to the procedures described in Example 11, using stearic acid in place of alpha-Tocopheryloxyacetic Acid (AcVitE) (8), a coupling protocol employing HATU/DIEA at 50 C. for 30 min and NMP as solvent in place of DMF in step 2. The crude linear peptide was purified and cyclized according to the modification described in Example 19, using a gradient of 20-80% B. Final product purification was performed using a gradient of 20-80% B (30 mpm) over 36 min.
  • 54
  • [ 506-30-9 ]
  • C34H39N4O7PolS [ No CAS ]
  • [ 109425-51-6 ]
  • Nα-Fmoc-Arg(Ng-Pbf)-OH [ No CAS ]
  • C68H116N28O10 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The synthesis of fatty acyl derivatives of linear (HR)4 peptides were carried on solid-phase.The peptide was synthesized using Fmoc-Arg(Pbf)-Wang resin (0.3 mmol, 750.0 mg, 0.40 mmol/g).Once, the linear peptide was assembled after coupling Fmoc-His(Trt)-OH (557.74 mg, 0.9 mmol) andFmoc-Arg(Pbf)-OH (583.90 mg, 0.9 mmol) alternatively using HBTU (341.32. mg, 0.9 mmol) andDIPEA (315 L, 1.8 mmol) in DMF for 1 h with Fmoc deprotection in between each coupling cycleusing 20% piperidine in DMF. After the last coupling was completed, the resin was washed with DMF(3 15 mL) followed by N-terminal Fmoc deprotection using 20% piperidine in DMF (2 10 mL,10 min each). Then, lauric acid (180 mg, 0.9 mmol) was coupled to the N-terminal of the linear (HR)4peptide using HBTU (341.32. mg, 0.9 mmol) and DIPEA (315 L, 1.8 mmol) in the DMF. The resin was washed with DCM (3 25 mL) and methanol (3 25 mL) and vacuum dried. Then the resinand the side chain protecting groups were cleaved from the peptidyl resin using cleavage cocktailTFA/thioanisole/EDT/anisole (90:5:3:2, v:v:v:v, 15 mL) for 5 h. The crude peptide was precipitatedby adding cold diethyl ether (100 mL, Et2O) and centrifuged at 4000 rpm for 10 min, followed bydecantation to obtain the solid precipitate. The solid material was further washed with cold ether(2 100 mL) for 2 times. The peptide was resolubilized in a solvent (CH3CN + 0.1% TFA and water+ 0.1% TFA). The crude peptide was purified by using the reverse-phase high performance liquidchromatography (RP-HPLC) equipped with a Waters XBridgeTM BEH130 Prep C18 column OBDTM10 m (19 mm 250 mm). A gradient of 0-100% acetonitrile and water in 0.1% TFA (v/v) witha flow rate at 10.0 mL/min was used for the purification. The peptide powder was obtained afterlyophilization of pure HPLC fraction. Other fatty acid conjugates of (HR)4 were synthesized in asimilar manner
  • 55
  • [ 506-30-9 ]
  • C34H39N4O7PolS [ No CAS ]
  • [ 109425-51-6 ]
  • Nα-Fmoc-Arg(Ng-Pbf)-OH [ No CAS ]
  • C44H78N14O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The synthesis of fatty acyl derivatives of linear (HR)4 peptides were carried on solid-phase.The peptide was synthesized using Fmoc-Arg(Pbf)-Wang resin (0.3 mmol, 750.0 mg, 0.40 mmol/g).Once, the linear peptide was assembled after coupling Fmoc-His(Trt)-OH (557.74 mg, 0.9 mmol) andFmoc-Arg(Pbf)-OH (583.90 mg, 0.9 mmol) alternatively using HBTU (341.32. mg, 0.9 mmol) andDIPEA (315 L, 1.8 mmol) in DMF for 1 h with Fmoc deprotection in between each coupling cycleusing 20% piperidine in DMF. After the last coupling was completed, the resin was washed with DMF(3 15 mL) followed by N-terminal Fmoc deprotection using 20% piperidine in DMF (2 10 mL,10 min each). Then, lauric acid (180 mg, 0.9 mmol) was coupled to the N-terminal of the linear (HR)4peptide using HBTU (341.32. mg, 0.9 mmol) and DIPEA (315 L, 1.8 mmol) in the DMF. The resin was washed with DCM (3 25 mL) and methanol (3 25 mL) and vacuum dried. Then the resinand the side chain protecting groups were cleaved from the peptidyl resin using cleavage cocktailTFA/thioanisole/EDT/anisole (90:5:3:2, v:v:v:v, 15 mL) for 5 h. The crude peptide was precipitatedby adding cold diethyl ether (100 mL, Et2O) and centrifuged at 4000 rpm for 10 min, followed bydecantation to obtain the solid precipitate. The solid material was further washed with cold ether(2 100 mL) for 2 times. The peptide was resolubilized in a solvent (CH3CN + 0.1% TFA and water+ 0.1% TFA). The crude peptide was purified by using the reverse-phase high performance liquidchromatography (RP-HPLC) equipped with a Waters XBridgeTM BEH130 Prep C18 column OBDTM10 m (19 mm 250 mm). A gradient of 0-100% acetonitrile and water in 0.1% TFA (v/v) witha flow rate at 10.0 mL/min was used for the purification. The peptide powder was obtained afterlyophilization of pure HPLC fraction. Other fatty acid conjugates of (HR)4 were synthesized in asimilar manner
  • 56
  • [ 506-30-9 ]
  • C34H39N4O7PolS [ No CAS ]
  • [ 109425-51-6 ]
  • Nα-Fmoc-Arg(Ng-Pbf)-OH [ No CAS ]
  • C56H97N21O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The synthesis of fatty acyl derivatives of linear (HR)4 peptides were carried on solid-phase.The peptide was synthesized using Fmoc-Arg(Pbf)-Wang resin (0.3 mmol, 750.0 mg, 0.40 mmol/g).Once, the linear peptide was assembled after coupling Fmoc-His(Trt)-OH (557.74 mg, 0.9 mmol) andFmoc-Arg(Pbf)-OH (583.90 mg, 0.9 mmol) alternatively using HBTU (341.32. mg, 0.9 mmol) andDIPEA (315 L, 1.8 mmol) in DMF for 1 h with Fmoc deprotection in between each coupling cycleusing 20% piperidine in DMF. After the last coupling was completed, the resin was washed with DMF(3 15 mL) followed by N-terminal Fmoc deprotection using 20% piperidine in DMF (2 10 mL,10 min each). Then, lauric acid (180 mg, 0.9 mmol) was coupled to the N-terminal of the linear (HR)4peptide using HBTU (341.32. mg, 0.9 mmol) and DIPEA (315 L, 1.8 mmol) in the DMF. The resin was washed with DCM (3 25 mL) and methanol (3 25 mL) and vacuum dried. Then the resinand the side chain protecting groups were cleaved from the peptidyl resin using cleavage cocktailTFA/thioanisole/EDT/anisole (90:5:3:2, v:v:v:v, 15 mL) for 5 h. The crude peptide was precipitatedby adding cold diethyl ether (100 mL, Et2O) and centrifuged at 4000 rpm for 10 min, followed bydecantation to obtain the solid precipitate. The solid material was further washed with cold ether(2 100 mL) for 2 times. The peptide was resolubilized in a solvent (CH3CN + 0.1% TFA and water+ 0.1% TFA). The crude peptide was purified by using the reverse-phase high performance liquidchromatography (RP-HPLC) equipped with a Waters XBridgeTM BEH130 Prep C18 column OBDTM10 m (19 mm 250 mm). A gradient of 0-100% acetonitrile and water in 0.1% TFA (v/v) witha flow rate at 10.0 mL/min was used for the purification. The peptide powder was obtained afterlyophilization of pure HPLC fraction. Other fatty acid conjugates of (HR)4 were synthesized in asimilar manner
  • 57
  • [ 506-30-9 ]
  • C34H39N4O7PolS [ No CAS ]
  • [ 109425-51-6 ]
  • Nα-Fmoc-Arg(Ng-Pbf)-OH [ No CAS ]
  • C80H135N35O12 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The synthesis of fatty acyl derivatives of linear (HR)4 peptides were carried on solid-phase.The peptide was synthesized using Fmoc-Arg(Pbf)-Wang resin (0.3 mmol, 750.0 mg, 0.40 mmol/g).Once, the linear peptide was assembled after coupling Fmoc-His(Trt)-OH (557.74 mg, 0.9 mmol) andFmoc-Arg(Pbf)-OH (583.90 mg, 0.9 mmol) alternatively using HBTU (341.32. mg, 0.9 mmol) andDIPEA (315 L, 1.8 mmol) in DMF for 1 h with Fmoc deprotection in between each coupling cycleusing 20% piperidine in DMF. After the last coupling was completed, the resin was washed with DMF(3 15 mL) followed by N-terminal Fmoc deprotection using 20% piperidine in DMF (2 10 mL,10 min each). Then, lauric acid (180 mg, 0.9 mmol) was coupled to the N-terminal of the linear (HR)4peptide using HBTU (341.32. mg, 0.9 mmol) and DIPEA (315 L, 1.8 mmol) in the DMF. The resin was washed with DCM (3 25 mL) and methanol (3 25 mL) and vacuum dried. Then the resinand the side chain protecting groups were cleaved from the peptidyl resin using cleavage cocktailTFA/thioanisole/EDT/anisole (90:5:3:2, v:v:v:v, 15 mL) for 5 h. The crude peptide was precipitatedby adding cold diethyl ether (100 mL, Et2O) and centrifuged at 4000 rpm for 10 min, followed bydecantation to obtain the solid precipitate. The solid material was further washed with cold ether(2 100 mL) for 2 times. The peptide was resolubilized in a solvent (CH3CN + 0.1% TFA and water+ 0.1% TFA). The crude peptide was purified by using the reverse-phase high performance liquidchromatography (RP-HPLC) equipped with a Waters XBridgeTM BEH130 Prep C18 column OBDTM10 m (19 mm 250 mm). A gradient of 0-100% acetonitrile and water in 0.1% TFA (v/v) witha flow rate at 10.0 mL/min was used for the purification. The peptide powder was obtained afterlyophilization of pure HPLC fraction. Other fatty acid conjugates of (HR)4 were synthesized in asimilar manner
  • 58
  • [ 74124-79-1 ]
  • [ 506-30-9 ]
  • [ 69888-87-5 ]
YieldReaction ConditionsOperation in experiment
100% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 40℃; for 1h; <strong>[506-30-9]Arachidic acid</strong> (1 g, 3.2 mmol, 1 eq) is dissolved in 100 ml of N, N-dimethylformamide, DMF.N, N-disuccinimidyl carbonate (DSC, 2.54 g, 9.6 mmol, 3 eq) and N, N-diisopropylethylamine Hunig base, 5.44 ml, 32 mmol, 10 eq), and the mixture was stirred at 40 C for 1 hour. After completion of the reaction, the compound was lyophilized to obtain Compound 2-2 (1.4 g, 100%)
  • 59
  • [ 334-48-5 ]
  • [ 506-30-9 ]
  • [ 616-29-5 ]
  • C33H66N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
10268] Compound 2-8 is dissolved in DMF and dichloromethane. DIEA and HI3TU are added thereto, and the mixture is stirred at room temperature. To the resulting suspended solution, Compound 1 is added at room tempera- tare, and the mixture was stirred. The activated solution of Compound 2-18 which is separately prepared [Compound 2-18 is dissolved in DMF and dichioromethane. DIEA and HI3TU are added thereto, and the mixture is stirred at room temperature] was added to the reaction vessel, and the mixture is stirred at room temperature. The mixture is heated to 40 C. and then stirred. To the reaction mixture, is added aqueous saturated sodium bicarbonate solution, the resulting solid is collected by filtration. The resulting solid is washed with water, acetonitrile and dichloromethane to obtain Compound 6-8,18.
  • 60
  • [ 506-30-9 ]
  • [ 616-29-5 ]
  • C43H86N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
10 g 10256] Compound 2-18 (13.9 g, 44.4 mmol, Tokyo Chemical Industry Co., Ltd.) was dissolved in DMF (207 mL) and dichioromethane (214 mL). DIEA (16.3 mL, 93 mmol) and HI3TU (18.5 g, 48.8 mmol) were added thereto, and the mixture was vigorously stirred at room temperature for 30 minutes. To the resulting suspended solution, Compound 1 (2.0 g, 22.2 mmol) was added at room temperature, and the mixture was vigorously stirred. Then, the mixture was heated to 40 C., and then stirred for 2 hours. To the reaction mixture, was added aqueous saturated sodium bicarbonate solution (10 mL), the resulting white solid was collected by filtration. The resulting solid was washed with water (100 mL), acetonitrile (100 mL) and dichloromethane (100 mL) to obtain Compound 3-18 (10.0 g, 14.7 mmol) as a white solid.10257] ?H-NMR (CDC13) oe:6.20 (brs, 2H), 3.96 (m, 1H),3.75 (m, 1H), 3.42 (m, 2H), 3.23 (m, 2H), 2.22 (m, 4H),1.68-1.20 (m, 68H), 0.88 (m, 6H)
  • 61
  • S6-amino-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)hexan-1-ol [ No CAS ]
  • [ 506-30-9 ]
  • C48H73NO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
494 mg 10316] To Compound 2-18 (466 mg, 1.490 mmol) in ethanol solution (5.0 mE), DMT-MM (471 mg, 1.702 mmol) was added, the mixture was stirred at room temperature for 15 minutes. The resulting reaction mixture was added to the crude product of Compound 12 in ethanol solution (2.5 mE), the mixture was stirred at room temperature for 4.5 hours. Afier the solvent was concentrated under reduced pressure, aqueous saturated sodium bicarbonate solution and water were added to the resulting residue, and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over sodium sulfate. The solvent was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate=70:30-20:80) to obtain Compound 13-18 (494 mg, Yield 62%) as colorless oil.10317] ?H-NMR (CDC13) oe: 7.41 (2H, d, J=7.2 Hz), 7.32-7.26 (6H, m), 7.21 (1H, t, J=7.2 Hz), 6.83 (4H, d, J=8.8 Hz),5.36 (1H, s), 3.79 (6H, s), 3.70-3.65 (1H, m), 3.63-3.57 (1H, m), 3.27 (1H, dd, J=9.2, 4.0 Hz), 3.24-3.13 (2H, m), 3.07 (1H, dd, J=9.2, 7.2 Hz), 2.45 (1H, t, J=5.6 Hz), 2.12 (2H, t, J=7.6 Hz), 1.78 (1H, s), 1.63-1.25 (40H, m), 0.88 (3H, t, J=6.8 Hz).
  • 62
  • [ 506-30-9 ]
  • (2S)-2-amino-N-dodecyl-5-[(N-nitrocarbamimidoyl)amino]pentanamide hydrochloride [ No CAS ]
  • N-[(1S)-1-(dodecylcarbamoyl)-4-[(N-nitrocarbamimidoyl)amino]butyl]icosanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% To a dichloromethane solution (10 mL) of icosanic acid (500 mg, 1.60 mmol) were added DMF (0.2 mL) and oxalyl dichloride (254 mg, 2.00 mmol), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated and the obtained residue was dissolved in THF (10 mL), added to a THF solution (20 mL) of the compound (870 mg, 2.06 mmol) obtained in Synthetic Example 1, step 2 and triethylamine (606 mg, 6.00 mmol) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (dichloromethane/methanol=40/1) and concentrated under reduced pressure. The obtained solid was washed with water and dried to give the title compound (920 mg, 1.35 mmol, yield 65%).
  • 63
  • [ 506-30-9 ]
  • [ 142217-69-4 ]
  • entecavir 5'-arachidate [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With diisopropyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; for 16h; DMF is a solvent and DIC is a condensing agent. Entecavir (1.0g) was reacted with arachidic acid (2.118g) for 16h at room temperature. A white solid precipitated, suction filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in an appropriate amount of methanol and subjected to silica gel column chromatography. Obtained a white solid, recrystallization from methanol gave 0.532 g of a white solid. Melting point: 185.7-188.6 C, yield 27.0%.
  • 64
  • [ 506-30-9 ]
  • [ 2400-66-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; water; sodium hydrogencarbonate; In dichloromethane; at 25 - 40℃;pH 8.5-9.5; 100 g (0.335 moles) of i-eicosonol (IV) and dichioromethane were added to a round bottom flask at 25-30 C. and temperature was raised to 35-40 C. to get the clear solution. The reaction mass was cooled to 25-30 C. and 0.47 g (0.003 moles) of (2,2,6,6-tetramethylpiperidin- i-yl)oxyl (TEMPO) was added. A mixture of 9-12% aqueous sodium hypochiorite and sodium bicarbonate solution (8%) were then added for 1-2 hours to maintain pH between 8.5 to 9.5. After completion of reaction, 40% aqueous sodium thiosulphate pentahydrate solution was added to the reaction mixture and stirred for 5 minutes at 25-30 C. The reaction mass was then extracted with dichloromethane and distilled off under reduced pressure till 6 volumes of dichloromethane remains. The intermediate Icosanal (III) so obtained can be immediately used in the next step. Purity %: 80.0
  • 65
  • [ 506-30-9 ]
  • [ 1240303-94-9 ]
  • C32H51N2O(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In water; N,N-dimethyl-formamide; acetonitrile; at 60℃; for 0.5h;Sealed tube; General procedure: Briefly, 20 muL of 4:1acetonitrile:dimethylformamide was added to the hydrolyzed TG fraction prepared above, followed by 20 muL 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC;640 mM in water), 10 muL hydroxybenzotriazole (20 mMin 99:1 acetonitrile:dimethylformamide), and 30 muL of AMPP coupling reagent (20 mM in acetonitrile). The resulting solution was vortexed, sealed, and heated at 60C for 30 min. After cooling to room temperature, 1 mL of methyl tert-butyl ether (MTBE) and 1 mL of water were added. The organic upper layer was then dried under N2 and reconstituted in 100 muL of 1:1 (v/v) methanol/chloroform for ESI-MS.
  • 66
  • [ 506-30-9 ]
  • [ 147-85-3 ]
  • C25H47NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% General procedure: Dicyclohexyl carbodiimide (DCC) (8.01 g, 38.8 mmol) and N-hydroxysuccinimide (NHS) (4.47 g, 38.8 mmol) are successively added to a solution of molecule A4 (10 g, 37 mmol) in THF (360 ml) at 0C. After stirring for 17 hours at room temperature, the medium is cooled to 0C. for 20 minutes, filtered through a sintered frit. L-Proline (4 g, 37.7 mmol), triethylamine (34 mL) and water (30 mL) are added to the filtrate. After stirring for 20 h at room temperature, the medium is treated with a 1N HCl aqueous solution to pH 1. The aqueous phase is extracted with dichloromethane (2125 mL). The combined organic phases are washed with an aqueous solution of 1 N HCl (2100 mL), water (100 mL), then a saturated aqueous solution of NaCl (100 mL). After drying over Na2SO4, the organic phase is filtered, concentrated under vacuum, and the residue is purified by chromatography on silica gel (cyclohexane, ethyl acetate, acetic acid) Yield: 9.2 g (72%)1H-NMR (CDCl3, ppm): 0.86 (6H); 1.14 (2H); 1.22-1.38 (20H); 1.50 (1H); 1.67 (2H); 1.95-2.10 (3H); 2.34 (2H); 2.49 (1H); 3.47 (1H); 3.56 (1H); 4.61 (1H). LC/MS (ESI): 368.3; (calculated ([M+H]+): 368.6).
63% General procedure: Dicyclohexyl carbodiimide (DCC) (8.01 g, 38.8 mmol) and N-hydroxysuccinimide (NHS) (4.47 g, 38.8 mmol) are successively added to a solution of molecule A4 (10 g, 37 mmol) in THF (360 ml) at 0C. After stirring for 17 hours at room temperature, the medium is cooled to 0C. for 20 minutes, filtered through a sintered frit. L-Proline (4 g, 37.7 mmol), triethylamine (34 mL) and water (30 mL) are added to the filtrate. After stirring for 20 h at room temperature, the medium is treated with a 1N HCl aqueous solution to pH 1. The aqueous phase is extracted with dichloromethane (2125 mL). The combined organic phases are washed with an aqueous solution of 1 N HCl (2100 mL), water (100 mL), then a saturated aqueous solution of NaCl (100 mL). After drying over Na2SO4, the organic phase is filtered, concentrated under vacuum, and the residue is purified by chromatography on silica gel (cyclohexane, ethyl acetate, acetic acid) Yield: 9.2 g (72%)1H-NMR (CDCl3, ppm): 0.86 (6H); 1.14 (2H); 1.22-1.38 (20H); 1.50 (1H); 1.67 (2H); 1.95-2.10 (3H); 2.34 (2H); 2.49 (1H); 3.47 (1H); 3.56 (1H); 4.61 (1H). LC/MS (ESI): 368.3; (calculated ([M+H]+): 368.6).
  • 67
  • [ 506-30-9 ]
  • [ 99755-59-6 ]
  • rotigotine arachidate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% 31.2 g (0.1 mol) of arachidic acid was dissolved in 300 ml of dichloromethane (DCM) under nitrogen at room temperature, and 12.7 g (0.1 mol) of oxalyl chloride was added dropwise to the mixed solution, the resulting solution after completion of the reaction was referred to as Solution I; 31.5 g (0.1 mol) of rotigotine was dissolved in a mixed solution containing 15.2 g (0.15 mol) of triethylamine and 300 ml of dichloromethane (DCM), which was referred to as Solution II; Solution I was added dropwise to Solution II; the abovementioned reaction solution was washed with an equal volume of water after completion of the reaction, and the solvent of the organic phase was evaporated under reduced pressure evaporated to give a oil, which was subjected to the subsequent cooling to provide a white solid. The white solid was washed with an appropriate amount of ethanol to give a white-like wet solid; after the abovementioned wet solid was dissolved in ethyl acetate by thermal dissolution, methanol was added to give a clear solution, followed by complete crystalization upon cooling; the mixture was filtered, and the filter cake was washed with an appropriate amount of methanol to provide a white-like solid (43.3 g) in a yield of 70.0%, melting point 30-33 C. (0069) 1H NMR (CDCl3, 400 MHz) deltaH: 7.10 (m, 2H, H-7 & H-14), 6.96 (d, J=7.56 Hz, 1H, H-6), 6.91 (q, J=3.40, 5.08 Hz, 1H, H-15), 6.80 (t, J=3.92 Hz, 2H, H-8 & H-13), ?2.94 (m 4H, H-1 & H-4), 2.81 (m, 4H, H-19 & H-20), 2.53 (m, 5H, H-2, H-16 & H-22), 2.03 (m, 1H, H-3), 1.76 (m, 2H, H-23), 1.56 (m, 1H, H-3), 1.49 (m, 2H, H-39), 1.38 (m, 2H, H-17), 1.26 (m, 30H, H-24H-38), 0.88 (m, 6H, H-18 & H-40).
  • 68
  • [ 506-30-9 ]
  • nalmefene hydrochloride [ No CAS ]
  • (4aS,7aS,12bs)-3-(cyclopropylmethyl)-4a-hydroxy-7-methylene-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl icosanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
10.84% With oxalyl dichloride; triethylamine; N,N-dimethyl-formamide; In dichloromethane; at 0 - 25℃; for 12h; The title compound was synthesized according to the general Scheme 1 for the synthesis of nalmefene prodrugs. 1.1 g; 1H NMR (400 MHz, CDCl3): see . Briefly, to a solution of icosanoic acid (5 g, 16.00 mmol, 5.92 mL, 1 eq) in DCM (50 mL) was added DMF (116.93 mg, 1.6 mmol, 123.09 muL, 0.1 eq), cooled to 0 C., was add (COCl)2 (2.34 g, 18.40 mmol, 1.61 mL, 1.15 eq). TEA (4.86 g, 48.80 mmol, 6.68 mL, 3 eq) and (3R,4aS,7aS,12bS)-3-(cyclopropylmethyl)-7-methylene-2,4,56,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol (3.01 g, 8.00 mmol, 0.5 eq, HCl). The mixture was stirred at 25 C. for 12 hours. The reaction mixture was extracted with H20 (80 mL*1) and DCM (80 mL*2). The combined organic phase was washed with brine (60 mL*3), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The compound was purified by column chormoatrography (SiO2, petroleum ether/ethyl acetate=10/1 to 1:1. The compound [4aS,7aS,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-7-methylene-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl icosanoate] was 100% pure and obtained as a white solid (1.1 g, 10.84% yield).
  • 69
  • [ 506-30-9 ]
  • [ 629-92-5 ]
  • [ 201230-82-2 ]
  • 70
  • [ 1120-28-1 ]
  • [ 506-30-9 ]
YieldReaction ConditionsOperation in experiment
65.1 g With water; sodium hydroxide In tetrahydrofuran at 20 - 70℃; for 2h; 3 Example 3: Preparation of arachidic acid (III) To a solution of methyl arachidate (Ila) (80 g) and tetrahydrofuran (400 mL), water (160 mL was added. A solution of sodium hydroxide, prepared by slowly adding sodium hydroxide (16.17 g) in water (160 mL), was added to the above solution maintaining the temperature of the reaction mass at 20-40 °C. Water (80 mL) was further added to the reaction mass and heated to 60-70 °C. The reaction mass was stirred for 2 hours at the same temperature and cooled to 45-55 °C. Water (80 mL) was added to the reaction mass and the temperature of the reaction mass was cooled to 25-35 °C. The pH of the reaction mass was adjusted to 6.5-7.5 by slowly adding dilute hydrochloric acid (IN) and stirred the reaction mass for 2 hours and 30 minutes. The precipitated compound was filtered. The wet compound was added to a mixture of tetrahydrofuran (80 mL) and acetone (400 mL). The reaction mass was heated to 50-60 °C and stirred for 40 minutes. The reaction mass was cooled to 25-35 °C and stirred for 40 minutes. The reaction mass was further cooled to 5-10 °C and the precipitated compound was filtered, washed with acetone (80 mL) and dried at 40-50 °C under vacuum for 9 hours to afford the desired compound. Yield: 65.1 g (84.5%) Purity : 99.96%
Same Skeleton Products
Historical Records

Similar Product of
[ 506-30-9 ]

Chemical Structure| 335080-96-1

A1267967[ 335080-96-1 ]

Eicosanoic Acid-1-13C

Reason: Stable Isotope