(2S)-1-[(2S)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】50798

【品名】(2S)-1-[(2S)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylic acid

【CA登记号】

【分子式】C₁₅H₁₉NO₄

【分子量】277.3202

【元素组成】C 64.97% H 6.91% N 5.05% O 23.08%

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：(XXXV)

Treatment of ethyl lactate (XXXII) with benzyl bromide and silver oxide in DMF gives Bzl-Lac-OH (XXXIII), which is then coupled with H-Pro-OMe (XXXIV) by means of DEPC and then saponified with NaOH in MeOH to yield derivative (XXXV). Finally, didemnin B is obtained by coupling of intermediate (XXXI) with (XXXV) by means of BOPCl and Et3N, followed by debenzylation with HCO2H and Pd in MeOH.

参考文献中间体

合成目标

【1】 Harris, B.D.; et al.; Synthetic studies of didemnins. II. Approaches to statine diastereomers. Tetrahedron Lett 1987, 28, 25, 2837.
【2】 Hamada, Y.; et al.; Efficient total synthesis of didemnins A and B. J Am Chem Soc 1989, 111, 2, 669.
【3】 Hamada, Y.; Shioiri, T.; Anti-tumor active cyclic peptide derived from marine organism: Synthesis, conformation and bioactivity. Kagaku Zokan 1990, 118, 31.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXI)	50796	(2R)-N-[(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]-4-methyl-2-(methylamino)pentanamide		C₄₉H₇₈N₆O₁₂	详情	详情
(XXXII)	16659	ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate	687-47-8	C₅H₁₀O₃	详情	详情
(XXXIII)	50797	(2S)-2-(benzyloxy)propionic acid		C₁₀H₁₂O₃	详情	详情
(XXXIV)	29552	methyl (2S)-2-pyrrolidinecarboxylate	2133-40-6	C₆H₁₁NO₂	详情	详情
(XXXV)	50798	(2S)-1-[(2S)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylic acid		C₁₅H₁₉NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Removal of the Z protecting group of (XIV) by hydrogenation over Pd/C gives secondary amine (XV), which is then condensed with carboxylic acid derivative (XVI) by means of EDC to furnish benzyl-protected didemnin B (XX) (in turn, synthesis of (XVI) can be performed by coupling of O-benzyl lactyl azide (obtained from ethyl O-benzyl lactate (XVII)) with Pro-OMe (XVIII) to afford methyl ester (XIX), followed by saponification of the methyl ester with NaOH). Finally, didemnin B is obtained by hydrogenation of (XX) over Pd/C for benzyl group removal.

参考文献中间体

合成目标

【1】 Rinehart, K.L.; et al.; Total synthesis of didemnins A, B, and C. J Am Chem Soc 1987, 109, 22, 6846.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	50810	benzyl (1R)-1-[([(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin		C₅₇H₈₄N₆O₁₄	详情	详情
(XV)	50796	(2R)-N-[(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]-4-methyl-2-(methylamino)pentanamide		C₄₉H₇₈N₆O₁₂	详情	详情
(XVI)	50798	(2S)-1-[(2S)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylic acid		C₁₅H₁₉NO₄	详情	详情
(XVII)	50812	ethyl (2S)-2-(benzyloxy)propanoate		C₁₂H₁₆O₃	详情	详情
(XVIII)	29552	methyl (2S)-2-pyrrolidinecarboxylate	2133-40-6	C₆H₁₁NO₂	详情	详情
(XIX)	50813	methyl (2S)-1-[(2S)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylate		C₁₆H₂₁NO₄	详情	详情
(XX)	50811	(2S)-N-[(1R)-1-[([(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]amino)carbonyl]-3-methylbutyl]-1-[(2S)-2-(benzyloxy)propanoyl]-N-methyl-2-pyrrolidinecarboxamide		C₆₄H₉₅N₇O₁₅	详情	详情

Extended Information