KH-1266

Chemical Name: (5Z,7E)-17beta-[2(R)-(4-Ethyl-4-hydroxyhexyloxy)-1(R)-methylbutyl]-9,10-secoandrosta-5,7,10(19)-trien-1alpha,3beta-diol
项目整合开发状态: Biological Testing
项目研究机构: Leo (Originator)
合成路线:Reduction of vitamin D derivative (I) with NaBH4 in ethanol-THF affords alcohol (II),which is alkylated with propargyl bromide (III) and potassium tert-butoxide in the presence of a crown ether.The resulting propargyl ether (IV) is condensed with hexafluoroacetone,by means of butyl litium,to provide tertiary alcohol (V).This compound is then photochemically isomerized in the presence of anthracene as a sensitizer to give (VI).Final deprotection of TBDMS groups with tetrabutylammonium fluoride in THF yields the title compound.

合成路线:Vitamin D derivative (I) was condensed with ethyllithium al low temperature to give,after chromatographic separation of isomers,alcohol (II).Alkylation of (II) with 6-bromo-3-ethyl-3-(trimethylsilyloxy)hexane (III) and potassium tert-butoxide in the presence of a crown ether afforded ether (IV),which was then photochemically isomerized in the presence of anthracene as a sensitizer to give (V).Final deprotection of silyl groups of (V) with 5% hydrogen fluoride in ethyl acetate-acetonitrile yielded the title compound.