Synthesis of Side-Chain Locked Analogs of 1α,25-Dihydroxyvitamin D3 Bearing a C17 Methyl Group

A convergent synthesis of side-chain locked vitamin D analogs 3 and 4, which bind strongly in silico to the vitamin D receptor(VDR), is described. The synthetic approach features an SN2′-syn displacement of carbamates by cuprates to set the challenging quaternary stereogenic center at C17 and a Pd-catalyzed construction of the triene system in the presence of a diyne moiety.