New A-ring analogs of the hormone 1α,25-dihydroxyvitamin D3: (2′-hydroxymethyl)tetrahydrofuro[1,2-a]-25-hydroxyvitamin D3

Conceptually new, enantiomerically pure bicyclic tetrahydrofuro[1,2-a]-A-ring phosphine oxides (+)-4 and (−)-4 were successfully prepared from methyl 2-pyrone-3-carboxylate and (S)- or (R)-2-(tert-butyldimethylsilyloxy)methyl-2,3-dihydrofuran, respectively. In addition, (2′-hydroxymethyl)tetrahydrofuro[1,2-a]-25-hydroxyvitamin D33a and 3b as new A-ring-modified analogs of the natural hormone 1α,25-dihydroxyvitamin D3 were readily synthesized by using Lythgoe-type coupling of the A-ring phosphine oxides (+)-4 and (−)-4 with C,D-ring ketone (+)-5.

Graphical abstractDownload full-size image