The C4-functionalized 9,10-seco-5,7,10(19)-cholestatriene derivatives: Concise synthesis and characterization of novel vitamin D analogues with a four-membered heterocyclic ether

Two novel stereoisomeric 9,10-seco-steroids (3a,b) bearing a spiro-oxetane at the C2 position of the A-ring with an unconventional C4-hydroxy group have been designed and synthesized by a convergent manner. The requisite A-ring enyne precursors (±)-9 were prepared in excellent yield from our reported aldehyde 4 according to a five-step procedure. The absolute configurations at the C4-hydroxy groups of the targeted compounds (3a,b) were determined by the circular dichroism (CD) exciton chirality method using the corresponding benzoates of the C4-allylic alcohol. Preliminary biological characterization using the bovine thymus VDR suggested that the incorporation of a spiro-oxetane at the C2 position, in combination with a hydroxy group at the C4 position, had negative effects on the VDR affinity.