benzyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate -Drug Synthesis Database

【结构式】

【分子编号】18551

【品名】benzyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate

【CA登记号】

【分子式】C₁₃H₁₈N₂O₃

【分子量】250.2976

【元素组成】C 62.38% H 7.25% N 11.19% O 19.18%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

Condensation of protected fucopyranose (I) with Z-serine methyl ester (II) in the presence of trimethylsilyl triflate afforded fucosylated serine derivative (III). Then, selective elimination of benzyloxycarbonyl group was performed by hydrogenolysis in the presence of Pd/C to give amine (IV). Subsequent coupling with acid (V) using EDC and HOBt as the condensing reagents provided amide (VI). Hydrolysis of ester group of (VI) by treatment with LiI in pyridine gave acid (VII), which was condensed with glutamic acid derivative (VIII) to yield (IX). Finally, debenzylation of (IX) by hydrogenolysis in the presence of Pd(OH)2 provided the target compound.

参考文献中间体

合成目标

【1】 Kiyoi, T.; Kondo, H.; A stereoselective alpha-fucosylation reaction using 1-hydroxy 2,3,4-tri-O-benzyl-L-fucose donor for the practical synthesis of selectin blocker. Bioorg Med Chem Lett 1998, 8, 20, 2845.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	18544	(3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-ol		C₂₇H₃₀O₅	详情	详情
(II)	18545	methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropanoate	1676-81-9	C₁₂H₁₅NO₅	详情	详情
(III)	18546	methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-[[(2R,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl]oxy]propanoate		C₃₉H₄₃NO₉	详情	详情
(IV)	18547	methyl (2R)-2-amino-3-[[(2R,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl]oxy]propanoate		C₃₁H₃₇NO₇	详情	详情
(V)	18548	2-tetradecylhexadecanoic acid		C₃₀H₆₀O₂	详情	详情
(VI)	18549	methyl (2R)-2-[(2-tetradecylhexadecanoyl)amino]-3-[[(2R,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl]oxy]propanoate		C₆₁H₉₅NO₈	详情	详情
(VII)	18550	(2R)-2-[(2-tetradecylhexadecanoyl)amino]-3-[[(2R,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl]oxy]propionic acid		C₆₀H₉₃NO₈	详情	详情
(VIII)	18551	benzyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate		C₁₃H₁₈N₂O₃	详情	详情
(IX)	18552	benzyl (4S)-5-(methylamino)-5-oxo-4-[((2R)-2-[(2-tetradecylhexadecanoyl)amino]-3-[[(2R,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl]oxy]propanoyl)amino]pentanoate		C₇₃H₁₀₉N₃O₁₀	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Coupling of N-Boc-D-serine (I) with L-glutamic acid 1-methylamide 5-benzyl ester (II) by means of EDC and HOBt affords the dipeptide derivative (III). Subsequent glycosylation of the serine hydroxyl group of (III) with the perbenzylfucose donor (IV) in the presence of SnCl2 and AgOTf gives the alpha-glycoside (V). The N-Boc protecting group of (V) is removed under acidic conditions to furnish amine (VI), which is acylated by 2-tetradecylhexadecanoic acid (VII), yielding amide (VIII). The O-benzyl protecting groups of (VIII) are then removed by hydrogenolysis in the presence of Pearlman's catalyst, and the resultant carboxylic acid is finally converted to the corresponding arginine salt.

参考文献中间体

合成目标

【1】 Hiramatsu, Y.; Moriyama, H.; Koyoi, T.; Tsukida, T.; Inoue, Y.; Kondo, H.; Studies on selectin blockers. 6. Discovery of homologous fucose sugar unit necessary for E-selectin binding. J Med Chem 1998, 41, 13, 2302.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20126	(2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropionic acid		C₈H₁₅NO₅	详情	详情
(II)	18551	benzyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate		C₁₃H₁₈N₂O₃	详情	详情
(III)	60186	phenylmethyl 4-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-hydroxypropanoyl]amino}-5-(methylamino)-5-oxopentanoate		C₂₁H₃₁N₃O₇	详情	详情
(IV)	60187	1-{5-fluoro-3,4-bis[(phenylmethyl)oxy]tetrahydro-2-furanyl}ethyl phenylmethyl ether; 2-fluoro-3,4-bis[(phenylmethyl)oxy]-5-{1-[(phenylmethyl)oxy]ethyl}tetrahydrofuran		C₂₇H₂₉FO₄	详情	详情
(V)	60188	phenylmethyl 4-{[3-[(3,4-bis[(phenylmethyl)oxy]-5-{1-[(phenylmethyl)oxy]ethyl}tetrahydro-2-furanyl)oxy]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propanoyl]amino}-5-(methylamino)-5-oxopentanoate		C₄₈H₅₉N₃O₁₁	详情	详情
(VI)	60189	phenylmethyl 4-({2-amino-3-[(3,4-bis[(phenylmethyl)oxy]-5-{1-[(phenylmethyl)oxy]ethyl}tetrahydro-2-furanyl)oxy]propanoyl}amino)-5-(methylamino)-5-oxopentanoate		C₄₃H₅₁N₃O₉	详情	详情
(VII)	33399	2-methylpropionic acid	79-31-2	C₄H₈O₂	详情	详情
(VIII)	60190	phenylmethyl 4-({3-[(3,4-bis[(phenylmethyl)oxy]-5-{1-[(phenylmethyl)oxy]ethyl}tetrahydro-2-furanyl)oxy]-2-[(2-tetradecylhexadecanoyl)amino]propanoyl}amino)-5-(methylamino)-5-oxopentanoate		C₇₃H₁₀₉N₃O₁₀	详情	详情

Extended Information