Concise synthesis and biological activities of 2α-Alkyl- and 2α-(ω-Hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3

✍ Scribed by Shinobu Honzawa; Yoshitomo Suhara; Ken-ichi Nihei; Nozomi Saito; Seishi Kishimoto; Toshie Fujishima; Masaaki Kurihara; Takayuki Sugiura; Keizo Waku; Hiroaki Takayama; Atsushi Kittaka

• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 216 KB
• Volume: 13
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(03)00739-x

✦ Synopsis

We found a concise route to the Trost A-ring precursor enyne for synthesizing 2a-alkylated 1a,25-dihydroxyvitamin D 3 (1) from d-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2asubstitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2a-alkyl-and four analogues of 2a-(o-hydroxyalkyl)-20-epi-1a,25-dihydroxyvitamin D 3 (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.