公开(公告)号：EP1385846A2

公开(公告)日：2004-02-04

申请号：EP02733993.6

申请日：2002-04-17

申请人： ARIZONA BOARD OF REGENTS, A BODY CORPORATE OF THE STATE OF ARIZONA acting for and on behalf of ARIZONA STATE UNIVERSITY

发明人： PETIT, George, R. ,  ORR, Brian ,  DUCKI, Sylvie

IPC分类号： C07D471/00

CPC分类号： C07F9/6561 ,  Y02P20/55

摘要： A new and efficient synthesis of the (+)-pancratistatin phosphate prodrug 2a has been accomplished. Selective protection (tetraacetate 4) of (+)-pancratistatin (1a) was followed by phosphorylation (to 5) with dibenzyl chlorophosphite (prepared in situ from dibenzyl phosphite). Cleavage of the acetate (with sodium methoxide) and benzyl (by hydrogenolysis) protecting groups followed by concomitant reaction with two equivalents of sodium methoxide afforded good yield of disodium (+)-pancratistatin phosphate (2a). Further increases in yields of the prodrug (2a) were realized by avoiding heat in the final purification steps. Fourteen (2b-o) additional metal and ammonium derived phosphate prodrugs were also synthesized.