L-732531-药物合成数据库

【药物名称】L-732531

化学结构式(Chemical Structure):

参考文献No.	20292
标题:	O-Heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroaryl macrolides
作者:	Sinclair, P.J.; Goulet, M.; Wong, F.; Parsons, W.H.; Goulet, J.; Wyvratt, M.J. (Merck & Co., Inc.)
来源:	EP 0532088; JP 1994116274; US 5252732; WO 9305058

合成路线图解说明: Protection of 2-bromoethanol (I) upon treatment with 2-methoxypropene (II) gave a mixture of ketals (III) and (IV). This mixture was used for N-alkylation of 5-bromoindole (V) in the presence of KOH to afford, after ketal hydrolysis, 1-(2-hydroxyethyl)-5-bromoindole (VI) (1). Alternatively, compound (VI) was obtained by alkylation of 5-bromoindole (V) with ethylene oxide (VII) in the presence of NaOH in DMSO (2). The hydroxyl group of (VI) was then protected as the silyl ether (VII) by treatment with tert-butyldimethylsilyl chloride. Subsequent lithium-halogen exchange in (VIII) with tert-butyllithium, followed by reaction with bismuth trichloride provided the triindolyl bismuthane (IX) (1, 2). This was oxidized with either benzoyl peroxide (1) or peracetic acid (2) to produce the corresponding di(acyloxy) pentavalent bismuthanes (X).

合成路线图解说明: Arylation of ascomycin (XI) with the pentavalent bismuthanes (X) under catalysis of cupric acetate produced a mixture of the required indolyl ether (XII) and minor amounts of bis(indolyl) ether (XIII). Finally, after desilylation of (XII) and (XIII) by acid treatment in MeOH, the title monoindolyl ether was isolated by column chromatography.

参考文献No.	475823
标题:	Mild aryl ether formation in the semisynthesis of the novel macrolide immunosuppressant L-732,531
作者:	Brands, K.M.J.; et al.
来源:	J Org Chem 1998,63(19),6721

合成路线图解说明: Protection of 2-bromoethanol (I) upon treatment with 2-methoxypropene (II) gave a mixture of ketals (III) and (IV). This mixture was used for N-alkylation of 5-bromoindole (V) in the presence of KOH to afford, after ketal hydrolysis, 1-(2-hydroxyethyl)-5-bromoindole (VI) (1). Alternatively, compound (VI) was obtained by alkylation of 5-bromoindole (V) with ethylene oxide (VII) in the presence of NaOH in DMSO (2). The hydroxyl group of (VI) was then protected as the silyl ether (VII) by treatment with tert-butyldimethylsilyl chloride. Subsequent lithium-halogen exchange in (VIII) with tert-butyllithium, followed by reaction with bismuth trichloride provided the triindolyl bismuthane (IX) (1, 2). This was oxidized with either benzoyl peroxide (1) or peracetic acid (2) to produce the corresponding di(acyloxy) pentavalent bismuthanes (X).

合成路线图解说明: Arylation of ascomycin (XI) with the pentavalent bismuthanes (X) under catalysis of cupric acetate produced a mixture of the required indolyl ether (XII) and minor amounts of bis(indolyl) ether (XIII). Finally, after desilylation of (XII) and (XIII) by acid treatment in MeOH, the title monoindolyl ether was isolated by column chromatography.