ethyl (2S,3R)-3-methyl-2-oxiranecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】52089

【品名】ethyl (2S,3R)-3-methyl-2-oxiranecarboxylate

【CA登记号】

【分子式】C₆H₁₀O₃

【分子量】130.1436

【元素组成】C 55.37% H 7.74% O 36.88%

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：(III)

The title compound was isolated from the fermentation broth of Streptomyces sp. strain HC-21. A synthetic method for the preparation of the title compound was also reported. Asymmetric dihydroxylation of ethyl crotonate (I) using commercial AD-mix-beta produced diol (II). This was converted to the (2S,3R)-epoxide (III) by bromination with HBr in HOAc followed by cyclization of the resultant bromohydrin in the presence of DBU. Epoxide ring opening with the organomagnesium reagent generated from indole (IV) and methylmagnesium bromide furnished the chiral indolylbutanoate (V). Cyclization of the hydroxy ester (V) with guanidine hydrochloride (VI) in the presence of potassium tert-butoxide yielded the amino oxazolone (VII). Finally, displacement of the amino- by a methylamino group was achieved by treatment with aqueous methylamine.

参考文献中间体

合成目标

【1】 Kanamaru, T.; Nakao, M.; Tawada, H.; Kamiyama, K. (Takeda Chemical Industries, Ltd.); Oxazolone derivs. and their use as anti-Helicobacter pylori agent. EP 0923577; JP 1998279579; US 6169102; WO 9749703 .
【2】 Kamiyama, K.; Nakayama, Y. (Takeda Chemical Industries, Ltd.); Process for producing indolmycins. WO 9952905 .

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)	52087	Ethyl crotonate; trans-Ethyl crotonate; Crotonic acid ethyl ester	623-70-1	C₆H₁₀O₂	详情	详情
(II)	52088	ethyl (2S,3R)-2,3-dihydroxybutanoate		C₆H₁₂O₄	详情	详情
(III)	52089	ethyl (2S,3R)-3-methyl-2-oxiranecarboxylate		C₆H₁₀O₃	详情	详情
(IV)	15292	Indole; 1H-indole	120-72-9	C₈H₇N	详情	详情
(V)	52090	ethyl (2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoate		C₁₄H₁₇NO₃	详情	详情
(VI)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(VII)	52091	(5S)-2-amino-5-[(1R)-1-(1H-indol-3-yl)ethyl]-1,3-oxazol-4(5H)-one		C₁₃H₁₃N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of the chiral epoxide (I) with indole (II) by means of methylmagnesium bromide in ethyl ether/dichloromethane gives the indolylbutyric ester (III), which is hydrolyzed with NaOH in ethanol/water and purified by crystallization to yield the corresponding butyric acid (IV). The esterification of (IV) with ethanol/HCl regenerates pure ester (III), which is cyclized with guanidine (V) by means of tBu-OK in tert-butanol to afford the oxazolone (VI). Finally the amino group of (VI) is methylated by means of methylamine in water to provide the target indolmycin.

参考文献中间体

合成目标

【1】 Hasuoka, A.; et al.; Development of a stereoselective practical synthetic route to indolmycin, a candidate anti-H. pylori agent. Chem Pharm Bull 2001, 49, 12, 1604.

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)	52089	ethyl (2S,3R)-3-methyl-2-oxiranecarboxylate		C₆H₁₀O₃	详情	详情
(II)	15292	Indole; 1H-indole	120-72-9	C₈H₇N	详情	详情
(III)	52090	ethyl (2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoate		C₁₄H₁₇NO₃	详情	详情
(IV)	58332	(rac)-2-hydroxy-3-(1H-indol-3-yl)butanoic acid		C₁₂H₁₃NO₃	详情	详情
(V)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(VI)	52091	(5S)-2-amino-5-[(1R)-1-(1H-indol-3-yl)ethyl]-1,3-oxazol-4(5H)-one		C₁₃H₁₃N₃O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The condensation of trans-epoxide (I) with indole (II) gives the racemic indolylbutyric acid (III), which is submitted to optical resolution with (+)-alpha-phenylethylamine to yield the (2S,3R)-enantiomer (2S,3R) (III). Finally, this compound is cyclized with N,N'.dimethylguanidine (IV) by means of Et-ONa in refluxing ethanol to afford the target indolmycin.

参考文献中间体

合成目标

【1】 Preobrazhenskaya, M.N.; et al.; Total synthesis of antibiotic indolmycin and its stereoisomers. Tetrahedron 1968, 24, 6131.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(2S,3R)(III)	58333	(2S,3R)-2-hydroxy-3-(1H-indol-3-yl)butanoic acid		C₁₂H₁₃NO₃	详情	详情
(I)	52089	ethyl (2S,3R)-3-methyl-2-oxiranecarboxylate		C₆H₁₀O₃	详情	详情
(II)	15292	Indole; 1H-indole	120-72-9	C₈H₇N	详情	详情
(III)	58332	(rac)-2-hydroxy-3-(1H-indol-3-yl)butanoic acid		C₁₂H₁₃NO₃	详情	详情
(IV)	58334	N,N'-dimethylguanidine		C₃H₉N₃	详情	详情

Extended Information