合成路线1

1) The microbiological oxidation of 3beta-hydroxyandrost-5-en-17-one (I) gives 1alpha,3beta-dihydroxyandrost-5-en-17-one (II), which is silylated with tert-butyldimethylsilyl (TBS) chloride and imidazole to the bis(silyloxy) compound (III). The dehydrogenation of (III) by bromination with N-bromosuccinimide (NBS) and dehydrobromination with 2,4,6-trimethylpyridine (TMPyr) yields 1alpha,3beta-bis(tert-butyldimethylsilyloxy)androsta-5,7-dien-17-one (IV). The Wittig condensation of (IV) with ethyltriphenylphosphonium bromide (V) by means of NaH in DMS gives the corresponding ethylidene derivative (VI), which is treated first with 9-borabicyclo[3.3.1]nonane (9-BBN) and then with H2O2 and NaOH in THF yielding a mixture of the 20(S)- and 20(R)-isomers of 1alpha,3beta-bis(tert-butyldimethylsilyloxy)pregna-5,7-dien-20-ol that was separated by preparative TLC. The 20(S)-isomer (VII) was condensed with 1-bromo-3-butene (VIII) by means of NaH in refluxing xylene affording 20(S)-(3-butenyloxy)-1alpha,3beta-bis(tert-butyldimethylsilyloxy)pregna-5,7-diene (IX), which is oxidized with O2 gas in DMF/water catalyzed by Cu2Cl2 and PdCl2 to give the corresponding 3-oxobutoxy derivative (X). The Grignard alkylation of (X) with methylmagnesium bromide in THF afforded the 20(S)-(3-hydroxy-3-methylbutoxy) derivative (XI), which was submitted to UV irradiation with a 200 W high-pressure mercury lamp in ethanol yielding the silylated 22-oxavitamin D3 derivative (XII). Finally, this compound is desilylated by a treatment with tetrabutylammonium fluoride (TBAF) in THF. 2) The addition of ethyl acrylate (XIII) to the previously reported pregna-5,7-dien-20(S)-ol (VII) by means of tetrabutylammonium hydroxide/NaOH in water/toluene gives the 2-(ethoxycarbonyl)ethoxy derivative (XIV), which by alkylation of the carbonyl function with methyllithium yields the 3-hydroxy-3-methylbutoxy derivative (XI), already obtained. 3) The addition of N,N-dimethylacrylamide (XV) to the previously reported pregna-5,7-dien-20(S)-ol (VII) by means of NaH gives the corresponding propionamide derivative (XVI), which by a Grignard alkylation with methylmagnesium bromide and CeCl3 is converted into the 3-hydroxy-3-methylbutoxy derivative (XI), already obtained.