Progress toward a Convergent, Asymmetric Synthesis of Jervine

Abstract

Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland−Claisen rearrangement to establish the necessary cis-relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]­decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.

Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids

“…We next focused on the selective synthesis of E and Z alkenes with ketone 23. Treatment of ketone 23 with Wittig reagent [85][86][87] in THF in the presence of NaHMDS provided olefins 24 (isolated as the major isomer, 83% yield) and 25 (15% yield) in a 98% combined yield. Treatment of ketone 23 with Julia reagent 88 in THF altered the ratio and provided olefin 25 as the major isomer in 80% yield together with 24 (19% yield).…”

Enantioselective Total Synthesis of (−)-Zygadenine

“…However, the total syntheses of these natural products, particularly those with high-oxidation levels, have remained limited, despite major breakthroughs achieved over half a century ago and numerous reported synthetic studies of fragments . In 1967, Masamune’s group and Johnson’s group separately reported the syntheses of jervine ( 1 ) and veratramine ( 2 ). , Both studies relied on a C- nor -D- homo steroid ketone obtained through the degradation of hecogenin or veratramine.…”

Total Syntheses of Galanthamine and Lycoramine via a Palladium-Catalyzed Cascade Cyclization and Late-Stage Reorganization of the Cyclized Skeleton

“…Our synthetic studies began with the preparation of the precursor 10 (Scheme ). The deprotonation of racemic allylic alcohol 7 followed by intermolecular oxa-alkylation with freshly prepared benzylic bromide 9 in the presence of catalytic amounts of NaI provided the desired 10 in 82% yield. This transformation could be performed on a multigram scale.…”