Chemistry, bioactivity, biosynthesis, and total synthesis of stemmadenine alkaloids.

Covering: up to July 2022Stemmadenine alkaloids are a restrictive sub-group of monoterpene indole alkaloids, represented by two congeners: stemmadenine and vallesamine. Their skeleton is defined by the cleavage of the C-3-C-7 bond of the Strychnos group's pentacyclic scaffold in monoterpene indole alkaloids. The parent alkaloid stemmadenine acts as a key intermediate in the biosynthesis of several major monoterpene indole alkaloid families, including regular Strychnos alkaloids, Aspidosperma alkaloids, and Iboga alkaloids. In this review, a complete coverage of the stemmadenine alkaloids, from the early reports till the present day at 2022, are presented, and their diverse biological activities are briefly described. Moreover, the biosynthetic proposal for stemmadenine and the proposed biogenetic conversion of stemmadenine-type alkaloids into vallesamine-type congeners are discussed in detail. Moreover, the successful synthetic strategies to access the strained stemmadenine scaffolds are fully reviewed.

Six-Step Total Synthesis of (±)-Conolidine.

A concise total synthesis of (±)-conolidine, a potent nonopioid analgesic, in 19% overall yield is described here. A gold(I)-catalyzed Conia-ene reaction (Toste cyclization) and a Pictet-Spengler reaction served as key transformations for assembling the 1-azabicyclo[4.2.2]decane core and defining the geometry of the exocyclic double bond. The activation energies of formation of the vinyl-gold intermediates were calculated and revealed a silyl enol ether with an unprotected indole moiety as a suitable precursor for the Toste cyclization. This six-step synthesis did not involve any nonstrategic redox manipulations.