ChemInform Abstract: Diastereoselective Synthesis of Allosecurinine (III) and Viroallosecurinine from Menisdaurilide.

Abstract

Alkaloids U 0600Diastereoselective Synthesis of Allosecurinine (III) and Viroallosecurinine from Menisdaurilide. -The title compound is prepared in 42% overall yield starting from (+)-menisdaurilide (I). Following the same sequence, its enantiomer viroallosecurinine is available from (-)-(I). -(BARDAJI, G. G.; CANTO, M.; ALIBES, R.; BAYON, P.; BUSQUE*, F.; DE MARCH*, P.; FIGUEREDO, M.; FONT, J.; J.

Bio‐inspired Total Synthesis of Twelve Securinega Alkaloids: Structural Reassignments of (+)‐Virosine B and (−)‐Episecurinol A

“…Questions on the biosynthesis of the Securinega alkaloids have also fueled many investigations. The current hypotheses are based on the metabolism of tyrosine, and either lysine (for the construction of the 6‐membered A‐ring) or ornithine (5‐membered A‐ring) . The main difference between these hypotheses relates to the manner through which these primary precursors get connected, and more precisely, whether such events occur before or after the dearomatisation of the tyrosine‐derived phenolic intermediate (Scheme ).…”

“…An oxidative dearomatisation of the phenolic intermediates 15 would then give rise to the butenolide‐containing compounds 16 en route to (nor)securinane alkaloids by ketone reduction into 17 and intramolecular nucleophilic substitution events. More recently, Busqué and de March proposed that tyrosine is first dearomatised into the bicyclic butenolide‐containing intermediate 19 , which would then get connected to the cyclic imines 14 by a Mannich‐type reaction to furnish the same key precursors 17 (Scheme ). Busqué and de March showcased their hypothesis by achieving the total synthesis of both enantiomers of the securinane allosecurinine ( 4 , Figure ) through the use of a bicyclic butenolide intermediate of type 19 .…”

“…More recently, Busqué and de March proposed that tyrosine is first dearomatised into the bicyclic butenolide‐containing intermediate 19 , which would then get connected to the cyclic imines 14 by a Mannich‐type reaction to furnish the same key precursors 17 (Scheme ). Busqué and de March showcased their hypothesis by achieving the total synthesis of both enantiomers of the securinane allosecurinine ( 4 , Figure ) through the use of a bicyclic butenolide intermediate of type 19 . Later on, the efficiency of this strategy encouraged the group of Gademann to rely on the same approach in their own syntheses of Securinega alkaloids, while implementing an aza‐Michael annulation for the elaboration of the neo(nor)securinane cores (Scheme ) .…”

“…This approach could thus correspond to the true biosynthetic pathway toward these alkaloids. However, the diastereoselectivity of the Mannich reaction used by Busqué, de March and Gademann had the potential to afford 4 out of 8 possible diastereomers, and all with an exo ‐orientation of the methine C−H bond α to the nitrogen atom (Figure ). Thereby, this approach might not account for the biosynthesis of all possible (neo)(nor)securinane diastereomers, almost all of which having been identified from different plant extracts …”

The Securinega Alkaloids

“…62 The outcome of the synthesis, i.e. viroallosecurinine (4) or allosecurinine (3), depended on the choice of the key starting material, natural (À)-menisdaurilide (263) and its nonnatural (þ)-enantiomer (116), respectively.…”