Total synthesis of the Lycopodium alkaloid serratezomine A using free radical-mediated vinyl amination to prepare a β-stannyl enamine linchpin.

Serratezomine A is a member of the structurally diverse class of compounds known as the Lycopodium alkaloids. The key supporting studies and successful total synthesis of serratezomine A are described in this account. Significant features of the synthesis include the first application of free radical mediated vinyl amination and Hwu's oxidative allylation in a total synthesis and an intramolecular lactonization via a transannular S(N)i reaction.

Total synthesis of the lycopodium alkaloid (+)-serratezomine A.

The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the use of an oxidative allylation promoted by cerium(IV) (CAN) to establish the all-carbon quaternary chiral center with the proper configuration, and (d) an intramolecular substitution reaction to form the sensitive bridging lactone. Overall, 15 steps (longest linear sequence) are required to prepare the natural product from a commercially available aldehyde, and assembly of the contiguous array of six stereocenters is accomplished with high stereocontrol.

Total synthesis of buergerinin F and buergerinin G.

Syntheses of buergerinin F (1) and buergerinin G (2) were carried out to establish the absolute stereochemistry of these natural products. A linear sequence was used to synthesize 1 in 15 steps and 9% overall yield from thymidine. Subsequent oxidation of 1 with ruthenium tetroxide afforded 2 in 77% yield.

Synthesis of octyl arabinofuranosides as substrates for mycobacterial arabinosyltransferases.

A panel of octyl oligosaccharides comprised of arabinofuranose rings have been synthesized via efficient and readily scaleable routes. The key glycosylation reactions involved the coupling of octyl glycoside acceptors with the appropriate thioglycosides using N-iodosuccinimide and silver triflate activation. These syntheses were undertaken to provide substrates suitable for use in assays of mycobacterial arabinosyltransferases.