A Concise Synthesis of Lentiginosine Derivatives Using a Pyridinium Formation via the Mitsunobu Reaction

Rabah Azzouz (1) , Corinne Fruit (1) , Laurent Bischoff (1) , Francis Marsais (2)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 IRCOF - Institut de Chimie Organique Fine

A four-step synthesis of (−)-lentiginosine and its epimers is described starting from 2-bromopyridine. The key step consisted of a quaternarization of a fully unprotected pyridinium-polyol unit using Mitsunobu methodology. Subsequent PtO2-catalyzed diastereoselective hydrogenation of the pyridinium ring proceeded smoothly and led to the expected dihydroxyindolizidines with excellent yields. This stereochemically flexible strategy has been illustrated by the concise total synthesis of non-natural products derivatives such as (−)-lentiginosine and its stereoisomers in high yields.

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry; Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Radiochemistry; Chemical Sciences; Material chemistry; Chemical Sciences; Inorganic chemistry; Chemical Sciences; Catalysis

Rabah Azzouz, Corinne Fruit, Laurent Bischoff, Francis Marsais. A Concise Synthesis of Lentiginosine Derivatives Using a Pyridinium Formation via the Mitsunobu Reaction. Journal of Organic Chemistry, 2008, 73 (3), pp.1154-1157. ⟨10.1021/jo702141b⟩. ⟨hal-02385007⟩