新产品编号:1330971

Chemical Name: 1alpha,24(S)-Dihydroxy-25-nitrovitamin D3
项目整合开发状态: Biological Testing
项目研究机构: Teijin (Originator)
合成路线:Condensation of aldehyde (I) with 2-nitropropane (II) using tert-butyldimethylsilyl chloride,tetrabutylammonium fluoride and triethylamine afforded a mixture of diastereomeric nitroaldol products (III).After separation by column chromatography,the desired isomer was protected as the tert-butyldimethylsilyl ether (IV).Deprotection of the benzoate ester of (IV) was carried out by reduction with diisobutylaluminum hydride to provide alcohol (V),which was then oxidized to the corresponding ketone (VI) with pyridinium chlorochromate.Wittig reaction of (VI) with phosphorane (VII) provided the bromomethylene compound (VIII).

合成路线:Further exchange of the protecting group of (VIII) from tert-butyldimethylsilyl to trimethylsilyl ether (IX) was carried out by desilylation with LiBF4 and H2SO4,followed by treatment with (trimethylsilyl)imidazole.The resulting compound (IX) was cyclized with enyne (X) using Pd2(dba)3,Et3N and PPh3 to afford triene (XI),which was finally desilylated with pyridinium tosylate.

合成路线:Condensation of aldehyde (I) with 2-nitropropane (II) using tert-butyldimethylsilyl chloride,tetrabutylammonium fluoride and triethylamine afforded a mixture of diastereomeric nitroaldol products (III).After separation by column chromatography,the desired isomer was protected as the tert-butyldimethylsilyl ether (IV).Deprotection of the benzoate ester of (IV) was carried out by reduction with diisobutylaluminum hydride to provide alcohol (V),which was then oxidized to the corresponding ketone (VI) with pyridinium chlorochromate.Wittig reaction of (VI) with phosphorane (VII) provided the bromomethylene compound (VIII).

合成路线:Further exchange of the protecting group of (VIII) from tert-butyldimethylsilyl to trimethylsilyl ether (IX) was carried out by desilylation with LiBF4 and H2SO4,followed by treatment with (trimethylsilyl)imidazole.The resulting compound (IX) was cyclized with enyne (X) using Pd2(dba)3,Et3N and PPh3 to afford triene (XI),which was finally desilylated with pyridinium tosylate.