Total Synthesis of (+)‐Alstonlarsine A

Abstract

An enantioselective total synthesis of (+)‐alstonlarsine A (1), a monoterpenoid indole alkaloid possessing a unique pentacyclic skeleton as well as a rare biological activity, is achieved. The key step is an efficient domino sequence, comprising enamine formation followed by an inverse‐electron‐demand intramolecular dearomative Diels–Alder cycloaddition for the construction of 9‐azatricyclo[4.3.1.03,8]decane core. The key intermediate for this domino sequence was synthesized by a newly developed methodology, relying on indole C(2)‐H bond functionalization, combined with intramolecular Horner–Wadsworth–Emmons reaction. This tactical combination offers a new general entry into other (privileged) tricyclic frameworks possessing indole ring fused to 6‐, 7‐ or 8‐membered rings.

Total Synthesis of (+)-Alstonlarsine A: Old Reactions in Modern Alkaloids Synthesis

“…Having developed a suitable strategy for cyclohepta[ b ]indole synthesis, we proceeded with our total synthesis of (+)-alstonlarsine A ( 1 ). 21 The synthesis commenced by alkylation of β-lactam 58 with methyl iodide (Scheme 7 ) to produce almost exclusively one diastereoisomer of 59 . The subsequent aldol addition of the corresponding enolate to acetaldehyde gave a mixture of separable diastereoisomers 60 , thus solving one structural complexity element: formation of the all-carbon quaternary stereocenter.…”

Enantioselective Total Synthesis of (−)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy

“…However, a small number of MIAs have been isolated containing rearranged indole units in which the C2–C7 bond has been cleaved (carbon numbering follows that given in the isolation of these molecules). Many elegant total synthetic approaches to members of the MIA family have been disclosed, including those containing C2–C7 indole cleavage. , …”