Chemical Synthesis of Aspidosperma Alkaloids Inspired by the Reverse of the Biosynthesis of the Rhazinilam Family of Natural Products

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…The key feature of this strategy is the conversion of a highly substituted pyrrole into an architecturally complex pyrrolidine, which is the reverse of a proposed biosynthesis that oxidatively degrades 545 to 560 (Scheme 116). 182 Divergent syntheses of (+)-spegazzinine (562) and (À)-aspidospermine (563) were developed using an intramolecular [4 + 2]/[3 + 2] cycloaddition cascade. The key intramolecular cycloaddition cascade was done by heating 1,3,4-oxazole 564, producing pentacyclic intermediate 565 as a single diastereomer, which was converted to 566 and 567 through reductive oxido bridge opening (Scheme 117).…”

Enantioselective Total Syntheses of (−)‐Rhazinilam, (−)‐Leucomidine B, and (+)‐Leuconodine F

“…(À)-Rhazinilam (1), with its unique axially chiral tetracyclic structure and potent in vitro tubulin-binding properties, [4] has triggered substantial synthetic efforts. [5,6] Total syntheses of (À)-leucomidine B(2) 6 and (+ +)-leuconodine F( 3) [7] have been reported and there have been recent efforts towards the synthesis of members of the leuconodine family of natural products,w hich have an unusual [5.5.6.6]diazafenestrane system. [7,8] Although architecturally distinct, with different ring connectivity and topology,t hese natural products are all biogenetically derived from vincadifformine (4).…”

Synthesis of Natural Products and Pharmaceuticals via Catalytic CH Functionalization

“…In 2012, the Gaunt group also reported the synthesis of rhazinilam by using two metal-catalyzed C-H functionalizations (C-H borylation and C-H alkylation) of pyrroles (Scheme 16.13a) [27]. Although they had already accomplished the synthesis of rhazinicine, another congener of rhazinilam [28], the same strategy was applied to the synthesis of rhazinilam and kopsiyunnanine C3 and cleverly extended to the synthesis of aspidospermidine by using a reductive transannular cyclization.…”