| Abstract
| - An efficient synthesis of monoacylated 1α,25-dihydroxyvitamin D3 A-ring precursors 15, 16, 18,and 19 has been described through an enzymatic hydrolysis process. Candida antarctica A lipase(CAL-A) hydrolyzes the C-5 acetate ester in trans stereoisomers 9 and 13, with complete and highselectivity, respectively. In the case of cis isomers 11 and 14, Chromobacterium viscosum lipase(CVL) is the enzyme of choice, exhibiting opposite selectivity for these two enantiomers. This lipaseselectively catalyzes the hydrolysis at the C-3 acetate in diester 11 and at C-5 position in diester14. It is noteworthy that through a hydrolysis reaction CAL-A and CVL allow the synthesis of thefour A-ring monoacetylated precursors of 1α,25-dihydroxyvitamin D3, precursors which arecomplementary to those obtained by the enzymatic acylation process. In addition, with excellentyield CVL selectively hydrolyzes the C-3 chloroacetate ester instead of the C-5 acetate in diester22, a key intermediate in the synthesis of new A-ring modified 1α,25-dihydroxyvitamin D3 analogues.
|
