Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Abstract

Here, we report the first asymmetric total synthesis of (+)-talassimidine and (+)-talassamine, two hetidine-type C20-diterpenoid alkaloids. A highly regio- and diastereoselective 1,3-dipolar cycloaddition of an azomethine ylide yielded a chiral tetracyclic intermediate in high enantiopurity, thus providing the structural basis for asymmetric assembly of the hexacyclic hetidine skeleton. In this key step, the introduction of a single chiral center induces four new continuous chiral centers. Another key transformation is the dearomative cyclopropanation of the benzene ring and subsequent SN2-like ring opening of the resultant cyclopropane ring with water as a nucleophile, which not only establishes the B ring but also precisely installs the difficult-to-achieve equatorial C7–OH group.

Asymmetric Total Syntheses of (+)-Davisinol and (+)-18-Benzoyldavisinol: A HAT-Initiated Transannular Redox Radical Approach

“…Over the past decades, the above distinct profiles rendered hetisine-type diterpenoid alkaloids appealing yet formidable targets for synthetic studies . Surprisingly, although substantial advances were made toward the total syntheses of atisine, denudatine, , hetidine, and napelline subfamilies, only four hetisine alkaloids were conquered. In 2004, Muratake and Natsume achieved the first total synthesis of nominine ( 1 ) in 40 steps .…”

Divergent Total Syntheses of Napelline-Type C20-Diterpenoid Alkaloids: (−)-Napelline, (+)-Dehydronapelline, (−)-Songorine, (−)-Songoramine, (−)-Acoapetaldine D, and (−)-Liangshanone

“…These intriguing structural features rendered these C 20 -diterpenoid alkaloids challenging and attractive targets for synthetic chemists . During the past decades, remarkable achievements have been accomplished toward accessing ent -atisane diterpene-derived alkaloids such as atisines, hetidines, hetisines, denudatines, and arcutines . However, there has been limited success in the total synthesis of the ent -kaurenoid alkaloids. , …”

Total Synthesis and Structure Revision of (+)-Lancilactone C

“…In previous total syntheses, the bicyclo[4.1.0]­heptadiene skeleton related to IV has been constructed via intramolecular cyclopropanation of the benzene ring . However, the proposed novel approach features a regioselective intermolecular reaction in one pot.…”