Stereocontrolled Total Synthesis of (+)-Isolaurenidificin and (−)-Bromlaurenidificin

Abstract

We report the first total syntheses of (+)-isolaurenidificin (1) and (−)-bromlaurenidificin (2), the latest acetogenins of the 2,6-dioxabicyclo[3.3.0]­octane class. The synthesis features a completely stereoselective one-pot epimerization-ring contraction to establish the cis configuration with respect to C10–H and C12–H of the tetrahydrofuran ring. Six stereogenic centers and an olefin geometry were constructed in a highly stereoselective manner. Absolute configurations of the natural products were deduced by the comparison of NMR data and specific rotations.

Highly Stereodivergent Construction of a C2-Symmetric cis,cis- and trans,trans-2,6-Dioxabicyclo[3.3.0]octane Framework by Double Intramolecular Amide Enolate Alkylation: Total Synthesis of (+)-Laurenidificin and (+)-Aplysiallene

“…Despite the extensive studies by Wang and co-workers, the complete structure and absolute stereochemistry of the natural product remained undetermined until the very recent first asymmetric total synthesis of 3 was reported by Fujioka and co-workers . Overall, the interesting molecular architecture of these halogenated Laurencia natural products has attracted considerable attention from synthetic chemists, resulting in total syntheses. ,, …”

Sequential Nucleophilic Arylation/Ring-Contractive Rearrangement of N-Alkoxylactams

“…The reaction utilizing lactones and lactams would construct ring-contracted cyclic ethers and amines. For example, the oxy-Favorskii rearrangement of α-halo lactones ( 1 : Y = O) proceeds through the ring-opening and intramolecular S N 2-type cyclization of alkoxide intermediate B to provide α-acylated cyclic ethers ( 2 : Y = O) . However, the aza-Favorskii rearrangement of α-halo lactams is scarce .…”