By allylic oxidation of vitamin D2 (XXIII) with SeO2 and tert-butyl hydroperoxide in pyridine followed by purification by TLC over silicagel. The allylic oxidation of trans-vitamin D2 (XXIX) with SeO2, tert-butyl hydroperoxide and octahydroacridine in dichloromethane gives the trans-1alpha-hydroxyvitamin D2 (XXX), which is isomerized to the target compound by irradiation with UV light with anthracene as photosensitizer.
The silylation of vitamin D2 (XXIII) with TBDMS-Cl and imidazole in dichloromethane gives the silyl ether (XXIV), which is cyclized with N-sulfinyl-p-toluenesulfonamide yielding the Diels-Alder adduct (XXV). The oxidation of (XXV) with SeO2 and N-methylmorpholine-oxide in ethanol affords the trans-1alpha-hydroxy-3-O-(tert-butyldimethylsilyl)vitamin D2 (XXVI), which is irradiated with UV light in benzene containing anthracene yielding 1alpha-hydroxy-3-O-(tert-butyldimethylsilyl)vitamin D2 (XXVII). Finally, this compound is desilylated with TBAF in THF. The cyclization of the silyl ether (XXIV) can also be performed with Ts-N=Se=N-Ts yielding the corresponding adduct (XXVIII), which is oxidized with SeO2 as before to afford the trans-1alpha-hydroxy-3-O-(tert-butyldimethylsilyl) vitamin D2 (XXVI) already reported.
The methanolysis of vitamin D2 tosylate (XIV) gives the cyclovitamin (XV), which is oxidized with SeO2 and tert-butyl hydroperoxide in dichloromethane yielding the 1alpha-hydroxy cyclovitamin (XVI). The acylation of (XVI) with acetic anhydride affords the acetate (XVII), which is rearranged with TsOH in hot dioxane to provide 1alpha-acetodyvitamin D2 (XVIII). Finally, this com-pound is hydrolyzed with KOH in aqueous methanol.
The 25-hydroxyvitamin D2 (I) is converted into the cyclovitamin D2 acetate (II) according to known methods. The dihydroxylation of the methylene group of (II) with OsO4 in pyridine gives vicinal diol (III), which is oxidized with NaIO4 yielding the ketonic cyclovitamin (IV). The reduction of the ketonic group of (IV) with NaBH4 in ethanol/water affords the corresponding hydroxy derivative (V), which is treated with mesyl chloride and triethylamine to give the mesylate (VI). The reduction of (VI) with LiAlH4 in THF yields the 19-nor-cyclovitamin D (VII), which is treated with hot acetic acid to afford both monoacetates (VIII) and (IX), separated by HPLC. Finally, both monoacetates (VIII) and (IX) are hydrolyzed with KOH in methanol.
The Oppenauer oxidation of ergosterol (XIX) gives ergosta-4,6,22-trien-3-one (I), which is dehydrogenated with SeO2 to ergosta-1,4,6,22-tetraen-3-one (II). The epoxidation of (II) with H2O2 and NaOH in dioxane affords the 1alpha,2alpha-epoxide (XX), which is reduced with Li in liquid NH3 to give ergost-5-ene-1alpha,3beta-diol (XXI). The acylation of (XXI) with acetic anhydride and pyridine yields the diacetate (XXII), which is dehydrogenated by the bromination dehydrobromination method to provide the previously reported 1alpha-acetoxyergosteryl acetate (XII). The UV irradiation of (XII) with a high pressure Hg lamp gives the 1alpha-hydroxyvitamin D2 diacetate (XIII), which is finally, deacylated with KOH in methanol.
The reaction of ergosta-4,6,22-trien-3-one (I) with DDQ and 5-sulfosalicylic acid in refluxing dioxane gives ergosta-1,4,6,22-tetraen-3-one (II), which is acylated with isopropenyl acetate and Ts-OH in refluxing butyl acetate yielding 3-acetoxyergosta-1,3,5,7,22-pentaene (III). The reduction of (III) with calcium borohydridde in ethanol affords ergosta-1,5,7,22-tetraen-3beta-ol (IV), which is condensed with 4-phenyl-3H-4,5-dihydro-1,2,4-triazole-3,5-dione (V) in ethyl acetate yielding the Diels-Alder adduct (VI). The silylation of (VI) with TBDMS-Cl and imidazole affords the silyl ether (VII), which is epoxidized with MCPBA in chloroform giving the 1alpha,2alpha-22,23-diepoxide (VIII). The elimination of the silyl group with TBAF in THF gives the 3beta-alcohol (IX).
The reduction of (IX) with LiAlH4 in refluxing THF eliminates the Diels-Alder adduct and opens the 1alpha,2alpha-epoxide giving the 1alpha,2beta-diol (X), which is acylated with acetyl chloride in pyridine yielding the diacetoxy epoxide (XI). The reaction of (XI) with NaI and trifluoroacetic anhydride in acetonitrile/THF regenerates the 22,23-double bond affording 1alpha-acetoxyergosteryl acetate (XII), which is submitted to UV irradiation with a high pressure mercury lamp in ethyl ether to provide the diacetate of 1alpha-hydroxyvitamin D2 (XIII). Finally, this compound is deacylated with KOH in refluxing ethanol.