[ CAS No. 73548-77-3 ] {[proInfo.proName]}

Name: 73548-77-3|(S)-Methyl 6-(((benzyloxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)hexanoate|97%
Brand: Ambeed
SKU: A746900
Price: 20.0 USD
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2D 3D

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COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 73548-77-3 ]

CAS No. :	73548-77-3	MDL No. :	MFCD03788041
Formula :	C₂₀H₃₀N₂O₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PUJVYJATJHQXRX-INIZCTEOSA-N
M.W :	394.46	Pubchem ID :	11132998
Synonyms :		Chemical Name :	(S)-Methyl 6-(((benzyloxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)hexanoate

Calculated chemistry of [ 73548-77-3 ]

Physicochemical Properties

Num. heavy atoms :	28
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.55
Num. rotatable bonds :	15
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	104.17
TPSA :	102.96 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.46 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.02
Log Po/w (XLOGP3) :	3.17
Log Po/w (WLOGP) :	3.0
Log Po/w (MLOGP) :	2.15
Log Po/w (SILICOS-IT) :	2.64
Consensus Log Po/w :	2.8

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.45
Solubility :	0.14 mg/ml ; 0.000354 mol/l
Class :	Soluble
Log S (Ali) :	-5.0
Solubility :	0.00392 mg/ml ; 0.00000993 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.17
Solubility :	0.0027 mg/ml ; 0.00000684 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.67

Safety of [ 73548-77-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 73548-77-3 ]

* 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.

Upstream synthesis route of [ 73548-77-3 ]
Downstream synthetic route of [ 73548-77-3 ]

[ 73548-77-3 ] Synthesis Path-Upstream 1~5

1
[ 73548-77-3 ]
[ 2389-45-9 ]

Reference： [1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 10, p. 995 - 999
[2] Chemistry - A European Journal, 2014, vol. 20, # 5, p. 1258 - 1262

2
[ 73548-77-3 ]
[ 27894-50-4 ]

Reference： [1] Tetrahedron Letters, 1998, vol. 39, # 31, p. 5631 - 5634
[2] Patent: EP1903034, 2008, A1, . Location in patent: Page/Page column 7
[3] Chemical Biology and Drug Design, 2012, vol. 79, # 4, p. 459 - 469

3
[ 73548-77-3 ]
[ 55757-60-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With palladium on activated charcoal; hydrogen In methanol at 20℃; for 0.666667 h;	[0047] Intermediate 4 (839 mg, 2.1 mmol) was dissolved in methanol (15 mL). After adding Pd/C (catalytic amount), the mixture was stirred under hydrogen atmosphere at room temperature for 40 min. After confirming completion of the reaction by TLC (ethyl acetate:n-hexane=2:1), the reaction solution was filtered through a Celite pad. After evaporation under a reduced pressure, intermediate 5 (563 mg, q.y.) was obtained as a colorless oil, which was used as such in the next reaction.

Reference： [1] Patent: US2015/80551, 2015, A1, . Location in patent: Paragraph 0047
[2] Angewandte Chemie - International Edition, 2017, vol. 56, # 6, p. 1643 - 1647[3] Angew. Chem., 2017, vol. 129, # 6, p. 1665 - 1669,5
[4] Tetrahedron, 1982, vol. 38, p. 697
[5] Chemistry - A European Journal, 2011, vol. 17, # 18, p. 5011 - 5018
[6] European Journal of Organic Chemistry, 2002, # 23, p. 4063 - 4070
[7] Tetrahedron Letters, 1989, vol. 30, # 3, p. 313 - 316
[8] Journal of Medicinal Chemistry, 1984, vol. 27, # 7, p. 888 - 893
[9] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 18, p. 6349 - 6358
[10] Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 870 - 876
[11] Patent: WO2010/48582, 2010, A1, . Location in patent: Page/Page column 168
[12] Angewandte Chemie - International Edition, 2010, vol. 49, # 18, p. 3211 - 3214
[13] Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, # 17, p. 6793 - 6798
[14] Chemical Biology and Drug Design, 2012, vol. 79, # 4, p. 459 - 469
[15] Angewandte Chemie - International Edition, 2013, vol. 52, # 27, p. 7033 - 7037[16] Angew. Chem., 2013, vol. 125, # 27, p. 7171 - 7175,5
[17] Patent: US2014/243527, 2014, A1, . Location in patent: Paragraph 0123

4
[ 73548-77-3 ]
[ 82689-20-1 ]

Reference： [1] European Journal of Organic Chemistry, 2015, vol. 2015, # 12, p. 2654 - 2660
[2] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 5, p. 1921 - 1924

5
[ 73548-77-3 ]
[ 82689-20-1 ]

Reference： [1] Patent: US2002/22631, 2002, A1,

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Yield	Reaction Conditions	Operation in experiment
93%	In diethyl ether at 25℃; for 0.0833333h;
72%	In methanol; diethyl ether for 0.333333h; cooling;
	In diethyl ether

Yield	Reaction Conditions	Operation in experiment
	In methanol; benzene
1.0 g	In methanol at 20℃; for 0.333333h;
	With methanol at 20℃; for 1h;	9.I Example 9 Example 9 Step (I): Synthesis of Nα-butyloxycarbonyl-Nε-benzyloxycarbonyl-Lysin methyl ester (Boc-Lys(Cbz)-OMe) referred to the paper [Kobayashi et al., J. Org. Chem. 66:6626-6623(2001)]. 2 g of Nα-butyloxycarbonyl-Nε-benzyloxycarbonyl-Lysin (Boc-Lys(Cbz)-OH) was dissolved in 15 mL of trimethylsilydiazomethane, 10 mL of anhydrous methanol was added thereto, and then stirred at room temperature for 60 min. The reaction product was passed through 7.7 g of silica gel (Sigma Aldrich, Silical Davisil Grade 635, pore 60, 60-100 mesh) to obtain a filtrate. The filtrate was evaporated to obtain a light yellow Nα-butyloxycarbonyl-Nε-benzyloxycarbonyl-Lysin methyl ester (Boc-Lys(Cbz)-OMe).

Yield	Reaction Conditions	Operation in experiment
90%	With palladium diacetate; triethylamine In dichloromethane for 8h; Ambient temperature;
96 mg	With triethylamine In dichloromethane for 8h; Ambient temperature;

Yield	Reaction Conditions	Operation in experiment
99%	With 2,6-dimethylpyridine In dichloromethane Ambient temperature;
238 mg	With 2,6-dimethylpyridine In dichloromethane for 0.25h; Ambient temperature;

[ CAS No. 73548-77-3 ] {[proInfo.proName]}

Quality Control of [ 73548-77-3 ]

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Product Details of [ 73548-77-3 ]

Calculated chemistry of [ 73548-77-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 73548-77-3 ]

Application In Synthesis of [ 73548-77-3 ]

[ 73548-77-3 ] Synthesis Path-Upstream 1~5

[ 73548-77-3 ] Synthesis Path-Downstream 1~88

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Yield	Reaction Conditions	Operation in experiment
100%	With palladium on activated charcoal; hydrogen In methanol at 20℃; for 0.666667h;	3 3) Synthesis of Intermediate 5 [0047] Intermediate 4 (839 mg, 2.1 mmol) was dissolved in methanol (15 mL). After adding Pd/C (catalytic amount), the mixture was stirred under hydrogen atmosphere at room temperature for 40 min. After confirming completion of the reaction by TLC (ethyl acetate:n-hexane=2:1), the reaction solution was filtered through a Celite pad. After evaporation under a reduced pressure, intermediate 5 (563 mg, q.y.) was obtained as a colorless oil, which was used as such in the next reaction.
100%	With palladium 10% on activated carbon; hydrogen In methanol at 80℃;
93%	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 3h;

90%	With hydrogen In methanol at 25℃; for 48h;
85%	With palladium on carbon; hydrogen In methanol; dichloromethane for 0.5h;
62%	With hydrogen; acetic acid In methanol for 4h;
	With hydrogen In methanol Yield given;
	With hydrogen In methanol; acetic acid
	With hydrogen In methanol; ethyl acetate for 2h;
	Multi-step reaction with 2 steps 1: 96 mg / triethylamine / Pd(OAc)2 / CH₂Cl₂ / 8 h / Ambient temperature 2: n-Bu₄NF / tetrahydrofuran / 1 h / Ambient temperature
	With hydrogen In methanol at 20℃; for 3h;	33.4 (S)-methyl 6-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)hexanoate (8.6Og) was hydrogenated in 150 rnL MeOH over 5% palladium on activated carbon (1.08g) under 1 atm hydrogen at ambient temperature for 3 hours. The spent catalyst was removed by vacuum filtration through a celite pad which was washed with MeOH. The combined filtrate and wash were concentrated under reduced pressure, affording (S)-methyl 6-amino-2-(tert- butoxycarbonylamino)hexanoate (TU3000-128) as clear viscous oil. MS (ESI+): calcd. 261.17, found 261.20 (MH+). H-NMR (600MHz, CDC13): 1.328 (2H, m), 1.375 (9H, s), 1.390 (2H, m), 1.55 (IH, m), 1.74(1H, m), 2.623(2H, d, J= 6.9Hz), 3.671 (3H, s), 4.237 (IH, m), 5.007 (IH, m).
	With palladium on alumina; hydrogen In methanol at 20℃; for 4h;
	With palladium on activated charcoal; hydrogen In methanol
	With palladium 10% on activated carbon; hydrogen In methanol at 20℃;
	With palladium on activated charcoal; hydrogen In methanol
	With palladium on activated charcoal; hydrogen In methanol; ethyl acetate at 20℃; for 4h;	9.II Example 9 Example 9 Step (II): A total amount of Boc-Lys(Cbz)-OMe was dissolved in a mixed solvent of 40 ml of ethyl acetate and 40 ml of methanol, and then the resultant solution was stirred at room temperature for 4 hours under a hydrogen atmosphere while gradually adding 0.223 g of Pd/C. The reaction product was passed through 3.56 g of celite (Sigma Aldrich) to remove Pd/C, and was then washed with 20 ml of methanol (MeOH) two times to obtain a filtrate. The filtrate was evaporated to obtain light viscous solid Boc-Lys-OMe.
	With palladium 10% on activated carbon; hydrogen In methanol
	With palladium 10% on activated carbon; hydrogen In methanol for 8h;

Yield	Reaction Conditions	Operation in experiment
70%	With diisobutylaluminium hydride
	With diisobutylaluminium hydride
	With diisobutylaluminium hydride In toluene at -78℃;

920 mg	With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 0.25h;
	Multi-step reaction with 2 steps 1: NaBH₄, LiCl / ethanol; tetrahydrofuran 2: 77 percent / sulfur trioxide-pyridine complex, triethylamine / dimethylsulfoxide / 0.17 h / Ambient temperature

Yield	Reaction Conditions	Operation in experiment
95%	In tetrahydrofuran at 20℃; for 2h;
	In dichloromethane at 23℃; for 0.75h;
	at 20 - 22℃; for 0.5h;

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 19h;Inert atmosphere;	To a mixture of Boc-Lys(Cbz)-OH (5.0 g, 13.1 minol) and potassium carbonate (3.6 g, 26.3 minol) in dimethylformamide (10 mL) at 0 C was added dropwise a solution of methyliodide (1.23 mL, 19.7 minol) in dimethylformamide (5 mL), and the mixture stirred at 0 C for 10 min, then room temperature for 19 h. The mixture was then diluted with ethyl acetate, washed with water, then brine, dried over anhydrous magnesium sulfate, filtered and the solution concentrated in vacuo. Purification by column chromatography (EtOAc/hexanes, 1:2) afforded the title compound 62 (5.17 g, 99%) as a colourless oil.[aID207 +7.0 (c 0.682 in CHCI3) (lit32 +6.1 (c 2.90 in CHCI3)); 1H NMR (400 MHz, CDCI3) oe1.36-1.40 (2H, m, H-4), 1.43 (9H, s, Boc), 1.43 (9H, s, Boc), 1.49-1.53 (2H, m, H-5), 1.59-1.66 (1H, m, Hb-3), 1.77-1.80 (1H, m, Ha3), 3.15-3.20 (2H, m, H-6), 3.72 (3H, s, OMe),4.25-4.30 (1H, m, H-2), 4.90-4.94 (1H, m, NH), 5.09 (2H, s, CH2Ph), 5.10-5.15 (1H, m,NH), 7.30-7.35 (5H, m, 5 x Ph); 13C NMR (100 MHz, CDCI3) oe 22.4 (CH2, C-4), 28.3 (3 xCH3, Boc), 29.4 (CH2, C-3), 32.3 (CH2, C-5), 40.6 (CH2, C-6), 52.2 (CH3, OMe), 53.2 (CH,C-2), 66.6 (CH2, CH2Ph), 79.9 (C, Boc), 128.06 (2 x CH, Ph), 128.10 (CH, Ph), 128.5 (2 xCH, Ph), 136.6 (C, Ph), 155.5 (C, Boc), 156.5 (C, Cbz), 173.3 (C, C-i); vmax(cm1) 3343,2932, 1692, 1519, 1247, 1160, 1023, 750.
97%		To a solution of Boc-L-Lys(Z)OH (2.00 g, 5.2 mmol) in dry DMF (50 mL) was added Cs2CO3 (1.71 g, 5.2 mmol). The mixture was stirred at rt for 2 h. To the reaction mixture was then added dropwise methyl iodide (392 muL, 6.3 mmol) and the mixture was stirred at rt overnight. The solvent was removed in vacuo and the residue was dissolved in EtOAc (100 m L) and washed with saturated NaHCO3 solution water and brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude compound was purified on column of silica gel (2% MeOH/DCM) to give the subject compound (2.00 g, yield 97%). Intermediate 31 was characterized by the following spectroscopic data: 1H NMR (DMSO-d6, 300 MHz) delta (ppm) 7.34 (m, 5H), 7.23 (t, 1H), 4.99 (s, 2H), 3.91 (m, 1H), 3.60 (s, 3H), 3.34 (s, 2H), 2.96 (m, 2H), 1.56 (m, 2H), 1.37 (m, 11H), 1.32 (m, 2H).
97%		(S)-Methyl 6-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)hexanoate To a solution of Boc-L-Lys(Z)OH (2.00 g, 5.2 mmol) in dry DMF (50 mL) was added Cs2CO3 (1.71 g, 5.2 mmol). The mixture was stirred at rt for 2 h. To the reaction mixture was then added dropwise methyl iodide (392 muL, 6.3 mmol) and the mixture was stirred at rt overnight. The solvent was removed in vacuo and the residue was dissolved in EtOAc (100 mL) and washed with saturated NaHCO3 solution water and brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude compound was purified on column of silica gel (2% MeOH/DCM) to give the subject compound (2.00 g, yield 97%). Intermediate 31 was characterized by the following spectroscopic data: 1H NMR (DMSO-d6, 300 MHz) delta (ppm) 7.34 (m, 5H), 7.23 (t, 1H), 4.99 (s, 2H), 3.91 (m, 1H), 3.60 (s, 3H), 3.34 (s, 2H), 2.96 (m, 2H), 1.56 (m, 2H), 1.37 (m, 11H), 1.32 (m, 2H).

Yield	Reaction Conditions	Operation in experiment
65%	With bis(tri-n-butyltin)oxide In toluene at 70℃; for 36h;
	With methanol; sodium hydroxide Reflux;

Yield	Reaction Conditions	Operation in experiment
100%	With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	4.32 (S)-Methyl 2-amino-6-(benzyloxycarbonylamino)hexanoate To a solution of Boc-L-Lys(Z)OMe 31 (2.00 g, 12.6 mmol) in DCM (30 mL) was added 30 mL of TFA. The mixture was stirred at rt for 1 h. Then the solvent were removed in vacuo, the residue was coevaporated 3 times with toluene. The residue was precipitated in Et2O to give the subject compound (2.1 g, yield 100%). Intermediate 32 was characterized by the following spectroscopic data: 1H NMR (DMSO-d6, 300 MHz) δ (ppm) 8.45 (sl, 2H), 7.33 (m, 5H), 7.31 (t, 1H), 5.00 (s, 2H), 4.03 (m, 1H), 3.74 (s, 3H), 2.97 (m, 2H), 1.75 (m, 2H), 1.39 (m, 4H).
100%	With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	4 (S)-Methyl 2-amino-6-(benzyloxycarbonylamino)hexanoate (S)-Methyl 2-amino-6-(benzyloxycarbonylamino)hexanoate To a solution of Boc-L-Lys(Z)OMe 31 (2.00 g, 12.6 mmol) in DCM (30 mL) was added 30 mL of TFA. The mixture was stirred at rt for 1 h. Then the solvent were removed in vacuo, the residue was coevaporated 3 times with toluene. The residue was precipitated in Et2O to give the subject compound (2.1 g, yield 100%). Intermediate 32 was characterized by the following spectroscopic data: 1H NMR (DMSO-d6, 300 MHz) δ (ppm) 8.45 (sl, 2H), 7.33 (m, 5H), 7.31 (t, 1H), 5.00 (s, 2H), 4.03 (m, 1H), 3.74 (s, 3H), 2.97 (m, 2H), 1.75 (m, 2H), 1.39 (m, 4H).
92%	With aluminium trichloride In dichloromethane for 1h; Ambient temperature;

92%	With tin(II) trifluoromethanesulfonate In dichloromethane at 20℃; for 2h;
	Multi-step reaction with 2 steps 1: 238 mg / 2,6-lutidine / CH₂Cl₂ / 0.25 h / Ambient temperature 2: n-Bu₄NF / tetrahydrofuran / 1 h / Ambient temperature

Yield	Reaction Conditions	Operation in experiment
95%	With aluminium chloride doped on a neutral alumina for 0.0233333h; Irradiation;
	With hydrogenchloride; methanol	Oligopeptide Derivatives; The preparation of L-lysine containing di- and tripeptide building blocks (see Figure 14) is carried out in solution, using standard peptide coupling procedures. Formation of an amide bond between BOC-L-Lys(Z)-OH 44 and methyl 6-aminocaproate hydrochloride 48 with TBTU in DMF in the presence of triethylamine furnishes compound 49 in quantitative yields. Boc-L-Lys(Z)-OMe 45 can easily be converted to H-L-Lys(Z)-OMe 50 by standard Boc-deprotection in dry methanol containing anhydrous HCl. The benzyl carbamate proves to be stable under these conditions. Peptide coupling of 50 with 44 using TBTU leads to Boc-L-Lys(Z)-L-Lys(z)-OMe 51, a dipeptide suitable for catalytic reductive amination of both protected Ng-amino functionalities of the two lysine residues.
	With hydrogenchloride In 1,4-dioxane at 20℃; for 2h;

Yield	Reaction Conditions	Operation in experiment
70%	With hydrogen In methanol; water at 20℃;	1,5-Dideoxy-1,5-iminoxylitol Derivatives; For the synthesis of 1,5-dideoxy-1,5-iminoxylitol derivatives, easily available xylo-pentodialdose 40 is used as sugar component, as shown in Figure 21. Reductive amination of crude 40 with 45 and 49, respectively, in aqueous methanol in the presence of Pearlman's catalyst and hydrogen at ambient pressure and temperature furnishes the desired products 91 and 92 in yields of about 70%. Similar reaction of 40 with dilysine derivative 51 results in the formation of target compound 93 in high yield. Since xylo-pentodialdose 40 shows two aldehyde functionalities, the reductive amination procedure proceeds very fast, resulting in a shortening of the reaction time needed for complete conversion. Additionally, the achieved overall yields are higher than in the previously reported cases. The obtained iminosugars are meso-configured, showing a mirror plane as an element of symmetry.
128 mg	With Pearlman catalyst; hydrogen In methanol; water at 20℃; for 24h;

Yield	Reaction Conditions	Operation in experiment
1: 41% 2: 10%	With hydrogen In methanol for 44h;
		Reductive amination of ketoaldose 5 and Boc-L-Lys(z)-OMe 45, with concomitant cleavage of the Z-protecting group, furnishes the N-substituted 1,5-dideoxy-1,5-imino-D-glucitol 61 as well as the L-ido derivative 62 in a ratio of about 4:1. Although the Rf values of the reaction products are very similar, the obtained mixture of diastereomers can be separated by repeated column chromatography on silica gel. Moreover, reaction of 5 with compound 49 also results in a mixture of diastereomeric compounds 63 and 64.

Yield	Reaction Conditions	Operation in experiment
99%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 2h;Inert atmosphere; Cooling with ice;	[0045] Under an Ar atmosphere, Nalpha-(tert-butoxycarbonyl)-Nepsilon-(benzyloxycarbonyl)-L-lysine (3) (810 mg, 2.1 mmol) was dissolved in anhydrous DMF (2 mL) and anhydrous methanol (1 mL). To the solution were sequentially added 1-hydroxybenzotriazole monohydrate (390 mg, 2.6 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (490 mg, 2.6 mmol), and the mixture was ice-cooled and stirred for 2 hours. After confirming completion of the reaction by TLC (ethyl acetate alone), the reaction solution was poured into water and extracted with ethyl acetate (3×70 mL). The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution (70 mL), water (70 mL) and then saturated saline (70 mL), and dried over anhydrous magnesium sulfate. After evaporation under a reduced pressure, the obtained material was purified by flash column chromatography (ethyl acetate:n-hexane=1:4 to 1:2), to give intermediate 4 (839 mg, 99%) as a colorless oil. [0046] 1H-NMR (300 MHz, CDCl3) delta: 7.36-7.33 (m, 5H), 5.09 (s, 2H), 5.06 (s, 1H), 4.81 (s, 1H), 3.73 (s, 3H), 3.20 (q, 2H, J=6.5 Hz), 1.77-1.67 (m, 2H), 1.53-1.51 (m, 2H), 1.42-1.37 (m, 11H).
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; at 20℃;	Amino Acid Derivatives; In order to synthesize iminosugar-amino acid conjugates that contain just one single amino acid residue, different L-lysine and L-serine derivatives have to be prepared, following standard procedures (see Figure 13). Commercially available H-L-Lys(Boc)-OMe hydrochloride 41 can be used directly for reductive amination of the Nepsilon-amino function. Selective reaction of the Nepsilon-amino functionality can be achieved by the use of Boc-L-Lys(Z)-OMe 45, which can be prepared from Boc-L-Lys(Z)-OH 44 by simple treatment with TBTU and triethylamine in methanol at ambient temperature. For simultaneous reaction of both amino functions, L-lysine methyl ester dihydrochloride 43 can be used in the reductive amination process. Reaction of L-lysine hydrochloride 42 with SOCl2 in dry methanol furnishes the corresponding methyl ester dihydrochloride 43 in high yield. Although commercially available L-serine methyl ester hydrochloride 46 could be directly employed, Z-L-Ser-OMe 47 is prepared by treatment of 46 with benzyl chloroformate in pure DMF in the presence of triethylamine. Compound 47 is very easy to handle in the reductive amination process, since the addition of base is not necessary to deprotonate the hydrochloride, as it would be necessary for 46.

Yield	Reaction Conditions	Operation in experiment
89%	With ammonia In methanol Ambient temperature;
53%	With ammonia In methanol at -78 - 20℃; for 72h;

Yield	Reaction Conditions	Operation in experiment
51%	With hydrogen In methanol for 18h;
	With hydrogen In water at 20℃;	1-Deoxymannonojirimycin Derivatives; In analogy to D-xylo-hexos-5-ulose 5, crude D-lyxo-hexos-5-ulose 10 is used as sugar component in the reductive amination procedure according to the invention (Figure 17), using Pearlman's catalyst and hydrogen in aqueous methanol at ambient pressure and temperature. Reaction of 10 with the amino acid building blocks 45 and 49 furnishes the desired D-manno-configured products 71 and 72, respectively, in fair overall yields. In both cases the formation of the corresponding L-gulo-isomers is not observed.

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogen / Pd/C / methanol; ethyl acetate / 2 h 2: 1.3 g / 1-hydroxybenzotriazole hydrate; 1,3-dicyclohexylcarbodiimide; triethylamine / tetrahydrofuran / 50 h
	Multi-step reaction with 2 steps 1: hydrogen; palladium on activated charcoal / ethyl acetate; methanol / 4 h / 20 °C 2: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 2 h / 0 °C

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrogen / Pd/C / methanol; ethyl acetate / 2 h 2: 1.3 g / 1-hydroxybenzotriazole hydrate; 1,3-dicyclohexylcarbodiimide; triethylamine / tetrahydrofuran / 50 h 3: 142.6 mg / lithium hydroxide monohydrate / tetrahydrofuran; H₂O / 20 °C
	Multi-step reaction with 3 steps 1: hydrogen; palladium on activated charcoal / ethyl acetate; methanol / 4 h / 20 °C 2: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 2 h / 0 °C 3: lithium hydroxide monohydrate / tetrahydrofuran; water / 7 h / 20 °C

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 53 percent / NH₃ / methanol / 72 h / -78 - 20 °C 2.1: H₂ / 10 percent Pd/C / methanol / 0.5 h / 20 °C 2.2: MS 3 Angstroem / dimethylformamide; acetonitrile / 2 h / 20 °C 2.3: 73 percent / NaBH₄ / methanol; acetonitrile; dimethylformamide / 0.5 h
	Multi-step reaction with 4 steps 1: 89 percent / NH₃ / methanol / Ambient temperature 2: H₂ / Pd/C / methanol 3: molecular sieves 3 Angstroem / acetonitrile; dimethylformamide / 1 h / Ambient temperature 4: NaBH₄ / methanol

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1N NaOH 2: 99 percent 3: 1) 1,5-dimethoxynaphthalene, ammonia borane / 1) aqueous ethanol, UV irradiation, 2 h, 2) benzyloxycarbonylation
	Multi-step reaction with 2 steps 1: 90 percent / NMP / CH₂Cl₂ / 3 h 2: 7 percent / NMP / CH₂Cl₂ / -5 °C

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C / pH 10
	Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C
	Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C / pH 10

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C / pH 10 4: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C
	Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C 4: 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
	Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 3: lithium hydroxide / 1,4-dioxane / 20 °C / pH 10 4: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
	Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling