(2S)-2-amino-4-[[(3S)-3-amino-3-carboxypropyl]disulfanyl]butyric acid -Drug Synthesis Database

【结构式】

【分子编号】42169

【品名】(2S)-2-amino-4-[[(3S)-3-amino-3-carboxypropyl]disulfanyl]butyric acid

【CA登记号】

【分子式】C₈H₁₆N₂O₄S₂

【分子量】268.35812

【元素组成】C 35.81% H 6.01% N 10.44% O 23.85% S 23.9%

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：(X)

The reaction of tetrahydrofuran (I) with HBr gives 4-bromobutanol (II), which is oxidized with NaOCl and TEMPO to yield the aldehyde (III). The reaction of (III) with ethyleneglycol and Ts-OH provides the cyclic ketal (IV), which is submitted to a Grignard condensation with diethyl oxalate (V) and Mg to give the alpha-ketoester (VI). The hydrolysis of (VI) with LiOH yields the corresponding alpha-ketoacid (VII), which is submitted to a stereoselective amination with ammonia and phenylalanine dehydrogenase to afford 2(S)-amino-5-(1,3-dioxol-2-yl)pentanoic acid (VIII). The reaction of (VIII) with SOCl2 and Me-OH provides 2(S)-amino-5,5-dimethoxypentanoic acid methyl ester (IX). The reaction of L- homocystine (X) with Boc2O gives the N-protected-L-homocystine (XI), which is condensed with pentanoic ester (IX) to yield the dimeric adduct (XII). The cleavage of (XII) with dithiothreitol (DTT) affords the monomeric intermediate (XIII), which is finally cyclized by means of Ms-OH to provide the target pyrido[2,1-b][1,3]thiazepine intermediate (XIV).

参考文献中间体

合成目标

【1】 Patel, R.N.; Enzymatic synthesis of chiral intermediates for omapatrilat, an antihypertensive drug. Biomol Eng 2001, 17, 6, 167.

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)	41419	tetrahydrofuran	109-99-9	C₄H₈O	详情	详情
(II)	50608	Tetramethylene Bromohydrin; 4-Bromo-1-butanol;4-bromobutan-1-ol	33036-62-3	C₄H₉BrO	详情	详情
(III)	50609	4-bromobutanal		C₄H₇BrO	详情	详情
(IV)	50610	2-(3-bromopropyl)-1,3-dioxolane		C₆H₁₁BrO₂	详情	详情
(V)	17571	Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate	95-92-1	C₆H₁₀O₄	详情	详情
(VI)	50611	ethyl 5-(1,3-dioxolan-2-yl)-2-oxopentanoate		C₁₀H₁₆O₅	详情	详情
(VII)	50612	5-(1,3-dioxolan-2-yl)-2-oxopentanoic acid		C₈H₁₂O₅	详情	详情
(VIII)	50613	(2S)-2-amino-5-(1,3-dioxolan-2-yl)pentanoic acid		C₈H₁₅NO₄	详情	详情
(IX)	22504	methyl (2S)-2-amino-6,6-dimethoxyhexanoate		C₉H₁₉NO₄	详情	详情
(X)	42169	(2S)-2-amino-4-[[(3S)-3-amino-3-carboxypropyl]disulfanyl]butyric acid		C₈H₁₆N₂O₄S₂	详情	详情
(XI)	50614	(2S)-2-[[(benzyloxy)carbonyl]amino]-4-[((3S)-3-[[(benzyloxy)carbonyl]amino]-3-carboxypropyl)disulfanyl]butyric acid		C₂₄H₂₈N₂O₈S₂	详情	详情
(XII)	50615	dimethyl (7S,10S,17S,20S)-10,17-bis[[(benzyloxy)carbonyl]amino]-3,24-dimethoxy-9,18-dioxo-2,25-dioxa-13,14-dithia-8,19-diazahexacosane-7,20-dicarboxylate		C₄₂H₆₂N₄O₁₄S₂	详情	详情
(XIII)	50616	methyl (2S)-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-sulfanylbutanoyl)amino]-6,6-dimethoxyhexanoate		C₂₁H₃₂N₂O₇S	详情	详情
(XIV)	50617	(4S,7S,10aS)-4-[[(benzyloxy)carbonyl]amino]-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid		C₁₈H₂₂N₂O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reductive cleavage of L-homocystine (I) with sodium in liquid ammonia produced homocysteine, which was subsequently alkylated with 2-(N-benzyloxycarbonyl-amino)ethyl tosylate (II) to afford thioether (III). The benzyloxycarbonyl protecting group of (III) was cleaved with HBr to give diamine (IV). Finally, condensation with ethyl acetimidate (V) furnished the target amidine.

参考文献中间体

合成目标

【1】 Young, R.J.; et al.; Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine. Bioorg Med Chem Lett 2000, 10, 6, 597.
【2】 Beams, R.M.; Frend, A.J.; Drysdale, M.J.; Franzman, K.W.; Hodson, H.F.; Rees, D.D.; Knowles, R.G.; Sawyer, D.A. (Glaxo Wellcome plc); Nitric oxide synthase inhibitors. EP 0958277; JP 2000504041; WO 9830537 .

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)	42169	(2S)-2-amino-4-[[(3S)-3-amino-3-carboxypropyl]disulfanyl]butyric acid		C₈H₁₆N₂O₄S₂	详情	详情
(II)	42170	2-[[(benzyloxy)carbonyl]amino]ethyl 4-methylbenzenesulfonate		C₁₇H₁₉NO₅S	详情	详情
(III)	42171	(2S)-2-amino-4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)sulfanyl]butyric acid		C₁₄H₂₀N₂O₄S	详情	详情
(IV)	42172	(2S)-2-amino-4-[(2-aminoethyl)sulfanyl]butyric acid		C₆H₁₄N₂O₂S	详情	详情
(V)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情

Extended Information