Design and synthesis of novel 1,25-dihydroxyvitamin D3 analogues having a spiro-oxetane fused at the C2 position in the A-ring

Abstract Four structurally novel stereoisomeric analogues of 1,25-dihydroxyvitamin D 3 ( 3a – d ) bearing a spiro-oxetane fused at the C2 position of the A-ring have been designed and synthesised in a convergent manner. The requisite A-ring enyne precursors ( 13a , b ) for the vitamin D analogues ( 3a , b ) and ( 3c , d ), respectively, were synthesised from pentaerythritol according to an eleven-step procedure. Preliminary biological evaluation of the analogues using the bovine thymus vitamin D receptor (VDR) suggested that the incorporation of the spiro-oxetane moiety instead of a gem -dimethyl group at the C2 position had a beneficial effect on the VDR affinity.