Formal Syntheses of (±)‐Tuberostemospiroline and (±)‐Stemona‐lactam R and Total Synthesis of (±)‐Stemoamide

Abstract

The structure proposed for the putative Stemona alkaloid named as parvistemoamide (4 a or 4 b) has been questioned after revising the literature data and an attempted preparation of structure 4 a, which led to a 5 : 1 mixture of (±)‐stemoamide (1). Studies on the intramolecular Friedel‐Crafts alkylation of a furan 12 containing a Z double bond tethered to a precursor of a N‐acyliminium ion are reported. As shown for bromo substituted furan 31, the cyclization occurred when a 4‐carbon saturated tether was present, allowing for the formal syntheses of racemic tuberostemospiroline (2) and stemona‐lactam R (3).

Computer-aided key step generation in alkaloid total synthesis

“…We chose stemoamide (1, Fig. 1), isolated from Stemonaceae plants (12), as an ideal target molecule because its four stereocenters and fused-ring structure would challenge modern CASP (11), while its precedence in thirty-two historic and contemporary syntheses (13)(14)(15)(16)(17)(18)(19)(20)(21) provides a strong benchmark for comparison.…”