methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate -Drug Synthesis Database

【结构式】

【分子编号】31069

【品名】methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate

【CA登记号】

【分子式】C₁₅H₂₂N₂O₄

【分子量】294.35076

【元素组成】C 61.21% H 7.53% N 9.52% O 21.74%

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：(XVI)

The Wittig condensation of decanal (I) with phosphorane (II) in benzene gives trans-2-dodecenoic acid methyl ester (III), which by thermal Michael addition of benzylamine yields the protected beta-aminoester (IV). The debenzylation of (IV) with H2 over Pd/C in methanol affords the free aminoester (V), which is condensed with N-(tert-butoxycarbonyl)-L-valine (VI) by means of 1-[3-(dimethylamino)propyl]-1-ethyl carbodiimide (WSC) in dichloromethane to give the dipeptide (VII) as a diastereomeric mixture, from which the desired isomer (VIII) is isolated by crystallization. The deprotection of the amino group of (VIII) with TFA in dichloromethane affords the peptide (IX), which is coupled with the conveniently protected glycyl-L-lysine dipeptide (X) by means of WSC as before to give the tetrapeptide (XI). The hydrolysis of the methyl ester group of (XI) with LiOH in THF/methanol/water yields the acidic tetrapeptide (XII). The intermediate glycyl-L-lysine dipeptide (X) has been obtained by coupling N-(tert-butoxycarbonyl)glycine (XV) with Nomega-(benzyloxycarbonyl)-L-lysine methyl ester (XVI) by means of WSC as before to give dipeptide (XVI), which is submitted to alkaline hydrolysis to provide the intermediate dipeptide (X).

参考文献中间体

合成目标

【1】 Sakai, K.; Yoshioka, T.; Agematu, H.; Chiba, H.; Dobashi, K.; Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. III. Synthetic study of rhodopeptins. J Antibiot 1999, 52, 8, 710.

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)	31059	decanal	112-31-2	C₁₀H₂₀O	详情	详情
(II)	14686	2-phenyl-1,3-dioxane		C₁₀H₁₂O₂	详情	详情
(III)	31060	methyl (E)-2-dodecenoate		C₁₃H₂₄O₂	详情	详情
(IV)	31061	methyl 3-(benzylamino)dodecanoate		C₂₀H₃₃NO₂	详情	详情
(V)	31062	methyl 3-aminododecanoate		C₁₃H₂₇NO₂	详情	详情
(VI)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(VII)	31063	methyl 3-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)dodecanoate		C₂₃H₄₄N₂O₅	详情	详情
(VIII)	31064	methyl (3R)-3-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)dodecanoate		C₂₃H₄₄N₂O₅	详情	详情
(IX)	31065	methyl (3R)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]dodecanoate		C₁₈H₃₆N₂O₃	详情	详情
(X)	31066	(2S)-6-[[(benzyloxy)carbonyl]amino]-2-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)hexanoic acid		C₂₁H₃₁N₃O₇	详情	详情
(XI)	31067	methyl (9S,12S,15R)-9-(4-[[(benzyloxy)carbonyl]amino]butyl)-12-isopropyl-2,2-dimethyl-15-nonyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazaheptadecan-17-oate		C₃₉H₆₅N₅O₉	详情	详情
(XII)	31068	(9S,12S,15R)-9-(4-[[(benzyloxy)carbonyl]amino]butyl)-12-isopropyl-2,2-dimethyl-15-nonyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazaheptadecan-17-oic acid		C₃₈H₆₃N₅O₉	详情	详情
(XV)	18066	N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid	4530-20-5	C₇H₁₃NO₄	详情	详情
(XVI)	31069	methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate		C₁₅H₂₂N₂O₄	详情	详情
(XVII)	31070	methyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-([2-[(tert-butoxycarbonyl)amino]acetyl]amino)hexanoate		C₂₂H₃₃N₃O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Indoline-2-carboxylic acid (I) is converted into the N-Boc derivative (II) by treatment with Boc2O. Subsequent coupling of (II) with methyl indoline-2-carboxylate (III) by using 2-chloro-1-methylpyridinium iodide (CMPI) provides amide (IV). Hydrolysis of the methyl ester function of (IV) employing LiOH leads to carboxylic acid (V). This is then coupled to N-epsilon-(benzyloxycarbonyl)-lysine methyl ester (VI) in the presence of CMPI to furnish the title compound.

参考文献中间体

合成目标

【1】 Reichert, D.; Kutscher, B.; Bang, H.; Brune, K.; Quinkert, G.; Schaible, H.-G. (Asta Medica AG); Specific immunophilin ligands as antiasthmatics and immunosuppressants. DE 19616509; EP 0896580; JP 2000500776; WO 9741148 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	34308	ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate	C₁₁H₁₃NO₂	详情	详情
(II)	61011	1-(tert-butoxycarbonyl)-2-indolinecarboxylic acid	C₁₄H₁₇NO₄	详情	详情
(III)	61012	methyl 2-indolinecarboxylate	C₁₀H₁₁NO₂	详情	详情
(IV)	61013	tert-butyl 2-{[2-(methoxycarbonyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1-indolinecarboxylate	C₂₄H₂₆N₂O₅	详情	详情
(V)	61014	1-{[1-(tert-butoxycarbonyl)-2,3-dihydro-1H-indol-2-yl]carbonyl}-2-indolinecarboxylic acid	C₂₃H₂₄N₂O₅	详情	详情
(VI)	31069	methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate	C₁₅H₂₂N₂O₄	详情	详情

Extended Information