(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid -Drug Synthesis Database

【结构式】

【分子编号】62448

【品名】(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid

【CA登记号】

【分子式】C₁₆H₁₇NO₄S

【分子量】319.38132

【元素组成】C 60.17% H 5.37% N 4.39% O 20.04% S 10.04%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXIX)

Addition of phenylmagnesium bromide to cyclohexene oxide (XXI) in the presence of CuCl gave trans-2-phenylcyclohexanol (XXII), which was further esterified with chloroacetyl chloride to afford 2-phenylcyclohexyl chloroacetate (XXIII). Enantioselective hydrolysis of the racemic ester (XXIII) by means of Pseudomonas fluorescens lipase provided pure (1R,2S)-2-phenylcyclohexanol (XXIV), which was again esterified with chloroacetyl chloride, yielding the chiral ester (XXVI). Darzen's condensation of chloro ester (XXVI) with anisaldehyde (X) led to the chiral glycidic ester (XXVII). Epoxide ring opening in (XXVII) with 2-aminothiophenol (VII) furnished amino ester (XXVIII). Intermediate thiazepinone (VIII) was then obtained by cyclization of (XXVIII) using p-toluenesulfonic acid in refluxing xylene. Alternatively, amino ester (XXVIII) was first hydrolyzed to amino acid (XXIX), which was subsequently cyclized with p-toluenesulfonic acid as above (11). The final cyclization of amino acid (XXIX) to the intermediate thiazepinone (VIII) has also been carried out in the presence of trichloroacetic acid

参考文献中间体

合成目标

【1】 Plaum, M.J.M.; Boesten, W.H.J.; Process for the preparation of a benzothiazepine. EP 0796853; JP 1998007667; US 5859241 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(+/-)-(XXII)	51208	(1R,2S)-2-phenylcyclohexanol		C₁₂H₁₆O	详情	详情
(+/-)-(XXIII)	62445	(1S,2R)-2-phenylcyclohexyl 2-chloroacetate		C₁₄H₁₇ClO₂	详情	详情
(VII)	25182	2-aminobenzenethiol	137-07-5	C₆H₇NS	详情	详情
(VIII)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₁₆H₁₅NO₃S	详情	详情
(X)	27251	4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde	123-11-5	C₈H₈O₂	详情	详情
(XXI)	17986	7-oxabicyclo[4.1.0]heptane; cyclohexene oxide	286-20-4	C₆H₁₀O	详情	详情
(XXIV)	10492	(1S,2R)-(+)-trans-2-Phenyl-1-cyclohexanol; (1S,2R)-2-Phenylcyclohexanol	2362-61-0	C₁₂H₁₆O	详情	详情
(XXV)	62445	(1S,2R)-2-phenylcyclohexyl 2-chloroacetate		C₁₄H₁₇ClO₂	详情	详情
(XXVI)	62445	(1S,2R)-2-phenylcyclohexyl 2-chloroacetate		C₁₄H₁₇ClO₂	详情	详情
(XXVII)	62446	(1R,2S)-2-phenylcyclohexyl (2R,3S)-3-(4-methoxyphenyl)-2-oxiranecarboxylate		C₂₂H₂₄O₄	详情	详情
(XXVIII)	62447	(1R,2S)-2-phenylcyclohexyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate		C₂₈H₃₁NO₄S	详情	详情
(XXIX)	62448	(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid		C₁₆H₁₇NO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXIX)

A different strategy to reach the amino ester precursor (XXIX) was developed starting from the chiral diol (XXX), readily accessible by asymmetric dihydroxylation of cinnamate (I). Reaction of diol (XXX) with SOCl2 produced the cyclic sulfite (XXXI) (12,14). Optionally, diol (XXX) was condensed with phosgene to produce the cyclic carbonate (XXXII) (12). Opening of either sulfite (XXXI) or carbonate (XXXII) with 2-aminothiophenol (VIII) proceeded with retention of the configuration, leading to the desired intermediate aminoacid (XXIX)

参考文献中间体

合成目标

【1】 Lohray, B.B.; Jayachandran, B.; Bhushan, V.; Nandanan, E.; Ravindranathan, T.; Anchimeric assisted unprecedented SN(i)-type cleavage of cyclic sulfite: Application in the synthesis of the calcium channel blocker diltiazem. J Org Chem 1995, 60, 18, 5983.
【2】 Hulshof, L.A.; Kuilman, T.; Process for preparing 1,5-benzothiazepin derivs.. EP 0450705 .

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)	62431	ethyl (E)-3-(4-methoxyphenyl)-2-propenoate		C₁₂H₁₄O₃	详情	详情
(VIII)	25182	2-aminobenzenethiol	137-07-5	C₆H₇NS	详情	详情
(XXIX)	62448	(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid		C₁₆H₁₇NO₄S	详情	详情
(XXX)	62449	ethyl (2R,3S)-2,3-dihydroxy-3-(4-methoxyphenyl)propanoate		C₁₂H₁₆O₅	详情	详情
(XXXI)	62450	ethyl (4R,5S)-5-(4-methoxyphenyl)-2-oxo-1,3,2lambda~4~-dioxathiolane-4-carboxylate		C₁₂H₁₄O₆S	详情	详情
(XXXII)	62451	ethyl (4R,5S)-5-(4-methoxyphenyl)-2-oxo-1,3-dioxolane-4-carboxylate		C₁₃H₁₄O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXIX)

The key cis glycidate ester (XLIII) was prepared by (salen)Mn(III)-catalyzed asymmetric epoxidation of the cis cinnamate (XXXIX). Epoxide opening in (XLIII) with 2-nitrothiophenol (XLIV), with inversion of the configuration, led to the nitro ester adduct (XLV). The nitro group of (XLV) was then reduced to the aniline derivative (XLVI) by means of FeSO4. Subsequent isopropyl ester group saponification in (XLVI) furnished amino acid (XXIX). This was then cyclized to the target thiazepinone (VIII) in refluxing xylene

参考文献中间体

合成目标

【1】 Jacobsen, E.N.; Deng, L.; Furukawa, Y.; Martinez, L.E.; Enantioselective catalytic epoxidation of cinnamate esters. Tetrahedron 1994, 50, 15, 4323.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	62502	4-Picoline N-oxide; 4-Methyl-1-pyridiniumolate	1003-67-4	C₆H₇NO	详情	详情
(VIII)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₁₆H₁₅NO₃S	详情	详情
(XXIX)	62448	(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid		C₁₆H₁₇NO₄S	详情	详情
(XXXIX)	62458	isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate		C₁₃H₁₆O₃	详情	详情
(XLIII)	62459	isopropyl (2R,3R)-3-(4-methoxyphenyl)-2-oxiranecarboxylate		C₁₃H₁₆O₄	详情	详情
(XLIV)	62460	2-nitrobenzenethiol; 2-nitrophenylhydrosulfide		C₆H₅NO₂S	详情	详情
(XLV)	62461	isopropyl (2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₉H₂₁NO₆S	详情	详情
(XLVI)	62462	isopropyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate		C₁₉H₂₃NO₄S	详情	详情

Extended Information