Ns-strategy: Highly versatile synthesis of amines and its application to the syntheses of natural products

ORGN 445

Hideki Kobayashi, Wataru Kurosawa, Toshiyuki Kan, and Tohru Fukuyama. Graduate School of Pharmaceutical Sciences, University of Tokyo, 3-1, 7-Chome, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

We have recently developed a highly efficient and versatile synthetic method for amines using nitrobenzenesulfonamides (Ns-amides) as protecting-activating groups. N-Monosubstituted Ns-amides were converted to the N, N-disubstituted sulfonamides by conventional alkylation or Mitsunobu conditions. Efficient removal of the Ns group was carried out by treatment with soft nucleophiles, via Meisenheimer complexes, to give the corresponding secondary amines. One of the major advantages of this method is that both alkylation and deprotection proceed under very mild conditions. Philanthotoxin-343, which is the analog of a natural polyamine toxin, was synthesized by applying the strategy to the solid-phase synthesis. Furthermore, Ns-assisted macrocyclization proved to be effective to the construction of medium-sized cyclic amines.

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic 9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster Division of Organic Chemistry The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004