Synthesis of (+)‐Lentiginosine and Its Pyrrolizidine Analogue Based on Intramolecular Cyclization of α‐Sulfinyl Carbanions

Abstract

A synthesis of (+)‐lentiginosine and its pyrrolizidine analogue was accomplished in six steps, starting from L‐(+)‐tartaric acid. The key step of these syntheses involves the intramolecular cyclization of α‐sulfinyl carbanions for the construction of the indolizidine or pyrrolizidine ring.

Development of a Modified Julia Olefination of Imides for the Synthesis of Alkaloids

“…The most similar approach to the one presented here was recently reported by Pohmakotr et al using an intramolecular addition of a phenyl sulfoxide to an imide . This synthetic sequence involves the nucleophilic addition of an α‐sulfinyl carbanion, dehydration to the vinylsulfoxide, and reductive cleavage of the phenylsulfinyl group, to provide the analogous enamide lactam in a respectable 37 % overall yield.…”

Cyclization Strategies Using Imide Derivatives for the Synthesis of Polycyclic Nitrogen‐Containing Compounds

“…In this context, Pohmakotr and co-workers have also synthesized (+)-lentiginosine and an analogue using this same general cyclization strategy (i. e. addition of stabilized αcarbanions of sulfoxides onto cyclic imides). [84] Other remarkable synthetic strategies involving the cyclization of stabilized carbanions onto imides can be also based on direct enolate additions onto phthalimides [85] (or the use of neutral, highly nucleophilic enamine intermediates [86] ) or reaction cascades. Representative examples of reaction cascades include the work of Reyes, Tamariz and co-workers, who reported the preparation of pyrrolo[2,1-a]isoindol-5-ones starting from α-phthalimidoesters and electron-poor olefins; [87] and the work of Lu, Zhou and co-workers, who reacted phthalimidomalonates with electronpoor alkynes in the presence of a catalytic amount of Et 3 N to synthesize tricyclic 3-hydroxyisoindolin-1-one derivatives [88] (not shown).…”

“…In this context, Pohmakotr and co‐workers have also synthesized (+)‐lentiginosine and an analogue using this same general cyclization strategy ( i. e . addition of stabilized α‐carbanions of sulfoxides onto cyclic imides) [84] . Other remarkable synthetic strategies involving the cyclization of stabilized carbanions onto imides can be also based on direct enolate additions onto phthalimides [85] (or the use of neutral, highly nucleophilic enamine intermediates [86] ) or reaction cascades.…”

Recent Developments in the Synthesis of Polyhydroxylated Indolizidines

“…Synthesis of (+)-lentiginosine ( 4), Du-a-man and coworkers. [90] and nucleophilic substitution with sodium azide. Indolizidine ring was established using the Staudinger protocol, and final deprotection led to (À )-lentiginosine (ent-4) in 36 % overall yield and 12 steps from 74.…”

“…Du‐a‐man et al . reported a short synthesis of (+)‐lentiginosine ( 4 ), [90] which employs intramolecular cyclization of α‐sulfinyl carbanion to assemble indolizidine core (Scheme 11). [91] Authors previously utilized this method in the synthesis of several alkaloids, including (+)‐swainsonine ( ent ‐ 2 ) [92] .…”