Development of New Synthetic Methods and Its Application to Total Synthesis of Nitrogen-Containing Bioactive Natural Products

• Published in: Chemical & Pharmaceutical Bulletin Vol. 53; no. 11; pp. 1375 - 1386
• Main Author: Kibayashi, Chihiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.11.2005; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Alkaloids - chemical synthesis; Animals; Biological Products - chemical synthesis; Dendrobatid alkaloid; Humans; incarvillateine; marine alkaloid; Marine Toxins - chemical synthesis; new synthetic method; Nitrogen - chemistry; nitrogen-containing bioactive natural product; Pharmaceutical Preparations - chemical synthesis; Rats; total synthesis
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.53.1375

A group of naturally occurring substances containing nitrogen is widely distributed in plants as well as in fungi, animal, marine organisms, and insects, and many exhibit significant biological activity. These natural products with a huge variety of chemical structures include antibiotics, antitumor agents, immunostimulants, drugs affecting the cardiovascular and central nervous systems, analgesics etc. The diverse activities and low natural abundance of this group of natural products when coupled with their molecular complexity warrant development of new and efficient synthetic methods and strategy for the total synthesis of these products, in particular alkaloids. The purpose of this review is to describe some of our achievements in the total synthesis of the naturally-occurring bases including the Dendrobatid alkaloids pumiliotoxin B and allopumiliotoxin A, the anitibiotic streptazolin, the tricyclic marine alkaloids isolated from the ascidians such as fasicularin, lepadiformine, and cylindricine C, and the dimeric monoterpene alkaloid incarvillateine as well as the formal total synthesis of the spirocyclic marine alkaloids halichlorine and pinnaic acid, which are isolated from the Japanese marine sponge and the Okinawan bivalve, respectively.