抄録
Two novel stereoisomeric analogues of active vitamin D, 1,25-dihydroxyvitamin D_3, in which a spirooxetane structure exists at the C3 position of the A-ring, have been designed and synthesized in a convergent manner. This is the first attempt to utilize spiro-oxetane structures as surrogates of vital hydroxy groups in vitamin D analogues. The enyne precursors, which were required for the construction of the A-ring, were prepared from 3,3-bis(2-hydroxyethyl)oxetane in excellent yield according to the eight-step procedure. The absolute configuration at the C1-position of the synthesized compounds was determined by the circular dichroism exciton chirality method using the corresponding C1-allylic benzoates. The replacement of the C3-hydroxy group of active vitamin D with a spiro-oxetane structure provided more preferable conformation for its binding to vitamin D receptors by shifting the conformational equilibrium of the A-ring to its β-chair form.
