CHIRAL BUSINESS: Fine chemicals companies are jockeying for position to deliver the increasingly complicated chiral small molecules of the future

Abstract

THESE DAYS, WITH BIOPHARMACEUTICALS THE HOT TOPIC of the day, Peter Nagler sometimes brandishes the structure of apoptolidin. This natural product, originally isolated in 1997 from an actinomycete by researchers at the University of Tokyo, in Japan, is the subject of intense interest as a potential antitumor agent. A total synthesis was reported in 2001 by the group of K. C. Nicolaou at Scripps Research Institute. Worldwide, at least 10 other groups are developing more efficient routes. Amid the biopharma frenzy, we tend to forget that there are still many unsolved problems in chemistry," says Nagler, president of Degussa Fine Chemicals. Apoptolidin, which contains 25 chiral centers, exemplifies the complexity of molecules in pharmaceutical pipelines, he continues. "Everybody would prefer a flat, nonchiral molecule prepared in one step from benzene, but it doesn't work that way" Chirality in drugs is as old as the first natural-product therapeutic agents. Isolated as products of biological synthesis, drugs ...