Total synthesis of brevenal.

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of alpha-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner-Wadsworth-Emmons reaction, respectively, in a highly stereoselective manner.

Total synthesis of (-)-brevenal: a concise synthetic entry to the pentacyclic polyether core.

Total synthesis of (-)-brevenal, a novel marine polycyclic ether natural product, is described. Highly efficient and scalable entries to the AB-ring exo-olefin and the DE-ring enol phosphate and a rapid construction of the C-ring by means of our Suzuki-Miyaura coupling-based strategy realized a concise synthesis of the pentacyclic skeleton of (-)-brevenal. The present synthesis is considerably more efficient than our previous synthesis (longest linear sequence: 50 steps from 2-deoxy-d-ribose).

Convergent strategies for the total synthesis of polycyclic ether marine metabolites.

Marine polycyclic ether natural products continue to fascinate chemists and biologists due to their exceptionally large and complex molecular architectures and potent and diverse biological activities. Tremendous progress has been made over the past decade toward the total synthesis of marine polycyclic ether natural products. In this area, a convergent strategy for assembling small fragments into an entire molecule always plays a key role in successful total synthesis. This review describes our efforts to develop convergent strategies for the synthesis of polycyclic ethers and their application to the total synthesis of gambierol, gymnocin-A, and brevenal, and to the partial synthesis of the central part of ciguatoxins and the nonacyclic polyether skeleton of gambieric acids.

Total synthesis, structure revision, and absolute configuration of (-)-brevenal.

Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.

Total synthesis of the proposed structure of brevenal.

Total synthesis of the proposed structure of brevenal, a natural marine polycyclic ether product, has been accomplished. The synthesis features (i) convergent synthesis of the pentacyclic polyether skeleton using our developed Suzuki-Miyaura coupling strategy and (ii) construction of the multi-substituted dienal side chain by CuTC-mediated Stille reaction. Comparison of the NMR data of the synthetic compound with those reported for the natural product revealed that the proposed structure of brevenal needs to be revised.