L-732531
化合物 T32504Chemical Name: [1R,9S,12S(1'R,3'R,4'R),13R,14S,17R,21S,23S,24R,25S,27R]-17-Ethyl-1,14-dihydroxy-12-[2-[4-[1-(2-hydroxyethyl)-1H-indol-5-yloxy]-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18(E)-ene-2,3,10,16-tetraone
CAS No. 148365-48-4
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线: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: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.
📌 参考资料/链接：
参考文献标题:O-Heteroaryl,O-alkylheteroaryl,O-alkenylheteroaryl and O-alkynylheteroaryl macrolides
文献作者:Sinclair,P.J.; Goulet,M.; Wong,F.; Parsons,W.H.; Goulet,J.; Wyvratt,M.J.(Merck & Co.,Inc.)
参考来源:EP 0532088; JP 1994116274; US 5252732; WO 9305058
📄 详细内容
合成路线: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: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.
参考文献标题:Mild aryl ether formation in the semisynthesis of the novel macrolide immunosuppressant L-732,531
文献作者:Brands,K.M.J.; et al.
参考来源:J Org Chem 1998,63(19),6721
产品链接: CAS No. 148365-48-4››