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

Abstract

The so‐called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time‐efficient divergent synthesis enabled access to twelve of those alkaloids featuring (neo)(nor)securinane skeletons. Moreover, this work permitted to reassign the absolute configurations of (+)‐virosine B and (−)‐episecurinol A.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…Commercially available allosecurinine ( 3 ) would be a precursor to natural 12 and enantiomers of 13 and 14 . For the synthesis of natural antipodes of 13 and 14 , we planned to access viroallosecurinine ( 4 ) by total synthesis …”

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…After establishing the synthetic protocol to access (−)‐ 13 and (−)‐ 14 from 3 , we sought to access the natural enantiomers, (+)‐ 13 and (+)‐ 14 (Scheme ). We first synthesized a racemic mixture of menisdaurilide ( 60 ) following a five‐step synthetic protocol reported by Peixto and co‐workers . The racemate 60 was then reacted with enantiomerically enriched carboxylic acid 61 for the resolution, and diastereomer (−)‐ 62 was isolated in 35 % yield by flash column chromatography.…”

“…Commercially available allosecurinine (3) would be ap recursor to natural 12 and enantiomers of 13 and 14.For the synthesis of natural antipodes of 13 and 14,we planned to access viroallosecurinine (4)b yt otal synthesis. [21,22] Scheme 1. Biosynthetically relevant derivatizations of securinega alkaloids.…”

“…We first synthesized aracemic mixture of menisdaurilide (60)following afive-step synthetic protocol reported by Peixto and co-workers. [22] The racemate 60 was then reacted with enantiomerically enriched carboxylic acid 61 for the resolution, and diastereomer (À)-62 was isolated in 35 %y ield by flash column chromatography. Subsequent methanolysis of 62 produced (À)-menisdaurilide (60)i n9 0% yield and 93 % ee.…”

Biologically active indolizidine alkaloids

“…The extensive research on these alkaloids has included their separation, identification, synthesis and bioactivities, and the chemistry of indolizidine alkaloids, especially synthetic studies, was reviewed previously 4‐18 . More recent synthetic work has also been described 19‐24 . However, no systematic reports have been done on their biological and pharmacological activities, especially elucidation of mechanisms.…”