Synthesis of A-ring synthon of 2α-substituted vitamin d3 analogues utilizing Grignard reaction towards methyl 2,3-anhydro-4,6-o-benzylidene-α-D-manno-pyranoside
A concise route to the Trost A-ring precursor enyne for synthesizing 2α-substituted 1α,25-dihydroxyvitamin D3 (1) is described, in which the 2α-substituents could be introduced via addition reaction of Grignard reagent towards the sugar epoxide
Concise synthesis and biological activities of 2α-alkyl- and 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D 3
We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D3 (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω -hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3 (5b-d and 6a-d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.