(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid -Drug Synthesis Database

【结构式】

【分子编号】47774

【品名】(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid

【CA登记号】

【分子式】C₆H₁₄N₂O₃

【分子量】162.18884

【元素组成】C 44.43% H 8.7% N 17.27% O 29.59%

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)

Cyclization of 5(R)-hydroxy-L-lysine (VIII) by means of EDC and HOBt, followed by treatment of the resulting amino lactam (IX) with Boc2O, furnished the N-Boc aminolactam (X). The configuration of the (R)-secondary alcohol was inverted by Mitsunobu coupling with p-nitrobenzoic acid (XI) to produce the (S)-p-nitrobenzoate ester (XII). Methylation of the lactam N of (XII) yielded (XIII), and hydrolysis of the p-nitrobenzoate ester of (XIII) with LiOH afforded the (S)-hydroxy lactam (XIV). Esterification of (XIV) with myristic acid (XV) in the presence of EDC and DMAP produced the myristate ester (XVI). Treatment of (XVI) with trifluoroacetic acid removed the Boc protecting group to yield amine (XVII). This was then condensed with the intermediate lactone (VIII) in refluxing isopropanol to produce amide (XVIII). Finally, acetonide hydrolysis in (XVIII) employing trifluoroacetic acid generated the title compound.

参考文献中间体

合成目标

【1】 Kinder, F.R. Jr.; et al.; Total synthesis of bengamides B and E. J Org Chem 2001, 66, 6, 2118.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	47773	(4R,4aR,7R,7aS)-7-methoxy-2,2-dimethyl-4-[(E)-3-methyl-1-butenyl]tetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one		C₁₄H₂₂O₅	详情	详情
(VIII)	47774	(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid		C₆H₁₄N₂O₃	详情	详情
(IX)	47775	(3S,6R)-3-amino-6-hydroxy-2-azepanone		C₆H₁₂N₂O₂	详情	详情
(X)	47776	tert-butyl (3S,6R)-6-hydroxy-2-oxoazepanylcarbamate		C₁₁H₂₀N₂O₄	详情	详情
(XI)	18119	4-nitrobenzoic acid; p-nitrobenzoic acid	62-23-7	C₇H₅NO₄	详情	详情
(XII)	47777	(3S,6S)-6-[(tert-butoxycarbonyl)amino]-7-oxoazepanyl 4-nitrobenzoate		C₁₈H₂₃N₃O₇	详情	详情
(XIII)	47778	(3S,6S)-6-[(tert-butoxycarbonyl)amino]-1-methyl-7-oxoazepanyl 4-nitrobenzoate		C₁₉H₂₅N₃O₇	详情	详情
(XIV)	47779	tert-butyl (3S,6S)-6-hydroxy-1-methyl-2-oxoazepanylcarbamate		C₁₂H₂₂N₂O₄	详情	详情
(XV)	47780	myristic acid		C₁₄H₂₈O₂	详情	详情
(XVI)	47781	(3S,6S)-6-[(tert-butoxycarbonyl)amino]-1-methyl-7-oxoazepanyl myristate		C₂₆H₄₈N₂O₅	详情	详情
(XVII)	47783	(3S,6S)-6-amino-1-methyl-7-oxoazepanyl myristate		C₂₁H₄₀N₂O₃	详情	详情
(XVIII)	47782	(3S,6S)-6-[((2R)-2-[(4R,5R,6R)-5-hydroxy-2,2-dimethyl-6-[(E)-3-methyl-1-butenyl]-1,3-dioxan-4-yl]-2-methoxyethanoyl)amino]-1-methyl-7-oxoazepanyl myristate		C₃₅H₆₂N₂O₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Cyclization of (5R)-5-hydroxy-L-lysine (VIII) by means of EDC and HOBt afforded the caprolactam (IX). The amino group of (IX) was then protected as the N-Boc derivative (X) by treatment with Boc2O. Hydroxyl group acylation in (X) with cyclohexanecarbonyl chloride (XI) produced ester (XII). The Boc protecting group of (XII) was then removed by treatment with trifluoroacetic acid, yielding the aminocaprolactam (XIII). Coupling of amine (XIII) with lactone (VII) in refluxing isopropanol produced amide (XIV). The title compound was then obtained by acidic hydrolysis of the remaining acetonide function of (XIV).

参考文献中间体

合成目标

【1】 Kinder, F.R. Jr.; Versace, R.W.; Bair, K.W.; et al.; Synthesis and antitumor activity of ester-modified analogues of bengamide B. J Med Chem 2001, 44, 22, 3692.
【2】 Bair, K.W.; Kinder, F.R. Jr.; Jagoe, C.T. (Novartis AG); Certain substd. caprolactams, pharmaceutical compsns. containing them and their use in treating tumors. EP 1131297; WO 0029382 .
【3】 Bair, K.W.; Wattanasin, S.; Versace, R.W.; Kinder, F.R. Jr.; Jagoe, C.T. (Novartis AG); Certain substd. caprolactams, pharmaceutical compsns. containing them and a process for their preparation. US 6239127 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	54665	(4R,4aR,7R,7aS)-4-[(E)-3,3-dimethyl-1-butenyl]-7-methoxy-2,2-dimethyltetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one		C₁₅H₂₄O₅	详情	详情
(VIII)	47774	(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid		C₆H₁₄N₂O₃	详情	详情
(IX)	47775	(3S,6R)-3-amino-6-hydroxy-2-azepanone		C₆H₁₂N₂O₂	详情	详情
(X)	47776	tert-butyl (3S,6R)-6-hydroxy-2-oxoazepanylcarbamate		C₁₁H₂₀N₂O₄	详情	详情
(XI)	17220	cyclohexanecarbonyl chloride; Cyclohexanecarboxylic acid chloride	2719-27-9	C₇H₁₁ClO	详情	详情
(XII)	54666	(3R,6S)-6-[(tert-butoxycarbonyl)amino]-7-oxoazepanyl cyclohexanecarboxylate		C₁₈H₃₀N₂O₅	详情	详情
(XIII)	54667	(3R,6S)-6-amino-7-oxoazepanyl cyclohexanecarboxylate		C₁₃H₂₂N₂O₃	详情	详情
(XIV)	54668	(3R,6S)-6-[((2R)-2-{(4R,5R,6R)-6-[(E)-3,3-dimethyl-1-butenyl]-5-hydroxy-2,2-dimethyl-1,3-dioxan-4-yl}-2-methoxyethanoyl)amino]-7-oxoazepanyl cyclohexanecarboxylate		C₂₈H₄₆N₂O₈	详情	详情

Extended Information