Synthesis of two 6-s-cis locked stereoisomeric analogues of the steroid hormone 1 alpha,25-dihydroxyvitamin D-3: 1 alpha,25-dihydroxy-19-nor-previtamin D-3 and 1 beta,25-dihydroxy-19-nor-previtamin D-3

An efficient synthesis of A-ring precursors 8 and 9 from inexpensive commer cially available (-)-quinic acid has been developed. A-Ring synthon 8 has b een obtained through a short sequence (eight steps) in high overall yield ( 30%). One key step in the synthesis of A-ring precursor 9 is the selective deprotection of a silyl ether in an alpha,beta-unsaturated ester 12. Howeve r, of note is the excellent yield of the Mitsunobu process on derivative 15 , which takes place with the total inversion of configuration, giving ester 16. Coupling of A-ring synthons 8 and 9 with the appropriate CD-rings/side chain fragment 7, provides access to 6-s-cis locked analogues of the stero id hormone 1 alpha,25-(OH)(2)-D-3: 1 alpha,25-(OH)(2)-19-nor-pre-D-3 (3) an d novel 1 beta,25-(OH)(2)-19-nor-pre-D-3 (4). (C) 2000 Elsevier Science Ltd . All rights reserved.