26-Desmethyl-2-methylene-22-ene-19-nor-1伪,25-dihydroxyvitamin D₃ compounds selectively active on intestine

详细信息    查看全文

• 作者：Grazia Chiellini ; Pawel Grzywacz ; Lori A. Plum ; Margaret Clagett-Dame ; Hector F. DeLuca ; ^{deluca@biochem.wisc.edu" class="auth_mail}
• 关键词：Vitamin D ; Calcemic activity ; Transcription activity
• 刊名：Steroids
• 出版年：May, 2014
• 年：2014
• 卷：83
• 期：Complete
• 页码：27-38
• 全文大小：1585 K

文摘

Six new analogs of 2-methylene-19-nor-1伪,25-dihydroxyvitamin D₃, 6-7 and 8a,b-9a,b, have been synthesized. All compounds are characterized by a trans double bond located in the side chain between C-22 and C-23. While compounds 6 and 7 possess C-26 and C-27 methyls, compounds 8a,b and 9a,b lack one of these groups. A Lythgoe-based synthesis, employing the Wittig-Horner reaction was used for these preparations. Two different types of 螖²²E-25-hydroxy Grundmann鈥檚 ketone, having either only one stereogenic center located at position C-20 (20 and 21), or two stereogenic centers located at 20- and 25-positions (24a,b-25a,b) were obtained by a multi-step procedure from commercial vitamin D₂. The introduction of a double bond at C-22 appeared to lower biological activity in vitro and in vivo. Further removal of a 26-methyl in these analogs had little effect on receptor binding, HL-60 differentiation and CYP24A expression but markedly diminished or eliminated in vivo activity on bone calcium mobilization while retaining activity on intestinal calcium transport.