Synthetic study of biologically important nitrogen containing natural products: Development of new methodology and design of leading compounds for new pharmaceuticals

Abstract

Synthetic study of biologically important nitrogen-containing natural products and development of new methodologies and design of leading compounds for new pharmaceuticals are described. The first total synthesis of eudistomines, manzamine C, martefragin A, cerebroside B1b, and symbioramide was accomplished and the absolute configurations of the stereogenic centers were determined. A novel methodology useful for the synthesis of alkaloids that have perhydroisoquinoline ring system such as manzamine A and B, and related alkaloids, nakadomarin A and dynemicin A, is presented. Sphingolipids, 4-stereoisomers of 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, were synthesized and antimalaria activity was investigated. Inhibition of DNA primase by sphingosine and its analogues is described. A new synthetic methodology for alkylation and reduction of imines has been developed, and the first example of a reagent-controlled enantioselective Pictet-Spengler reaction is described. Also novel and convenient methods using transition metal and rare earth metals including alkene metathesis, asymmetric Diels-Alder reaction, imino ene reaction, selective allylic halogenation, enantioselective Pictet-Spengler reaction, and enantioselective physostigmine synthesis are described. © 2003 The Pharmaceutical Society of Japan.