http://www1.udel.edu/chem/polenova/PDF/Vanadium_haloperoxidases/VBPO_Bulter_NatProd2004.pdf

The Role of Vanadium Bromoperoxidase in the Biosynthesis of Halogenated Marine Natural Products

At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp(3) -hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

Stereoselective Halogenation in Natural Product Synthesis

Although there are many reagent combinations that can initiate polyene cyclizations, simple electrophilic halogen sources have not yet proven broadly effective as promoters of such processes. Herein is described a readily prepared and stable class of reagents capable of effecting such transformations for a wide range of electron-rich and -deficient terpenes derived from geraniol, farnesol, and nerol, thereby enabling the effective synthesis of a diverse array of complex chlorine-, bromine-, and iodine-containing polycyclic frameworks. Efforts to date have led to the first racemic laboratory total synthesis and structural revision of the anti-HIV natural product peyssonol A as well as an efficient and concise inaugural total synthesis of peyssonoic acid A. They have also permitted formal racemic total syntheses of aplysin-20, loliolide, K-76, and stemodin to be achieved through routes that are typically shorter, higher-yielding, and more environmentally conscious than previous efforts. Preliminary attempts to use chiral forms of the reagent class for enantioselective alkene halogenation are also described.

Simple Reagents for Direct Halonium-Induced Polyene Cyclizations

Natural Science Foundation of China [30530080]; Ministry of Science and Technology of China [2007AA09Z403]; Department of Science and Technology of Shandong Province [2006GG2205023]

http://ir.yic.ac.cn/bitstream/133337/9046/1/Halogenated%20Organic%20Molecules%20of%20Rhodomelaceae%20Origin-Chemistry%20and%20Biology.pdf

Halogenated Organic Molecules of Rhodomelaceae Origin: Chemistry and Biology

Marine red algae (Rhodophyta) are a rich source of bioactive halogenated natural products. The biogenesis of the cyclic halogenated terpene marine natural products, in particular, has attracted sustained interest in part because terpenes are the biogenic precursors of many bioactive metabolites. The first enzymatic asymmetric bromination and cyclization of a terpene, producing marine natural products isolated from red algae, is reported. Vanadium bromoperoxidase (V-BrPO) isolated from marine red algae (species of Laurencia, Plocamium, Corallina) catalyzes the bromination of the sesquiterpene (E)-(+)-nerolidol producing R-, ‚-, and A-snyderol and (+)-3‚-bromo-8-epicaparrapi oxide. R-Snyderol, ‚-snyderol, and (+)- 3‚-bromo-8-epicaparrapi oxide have been isolated from Laurencia obtusa, and each have also been isolated from other species of marine red algae. A-Snyderol is a proposed intermediate in other bicyclo natural products. Single diastereomers of ‚-snyderol, A-snyderol, and mixed diastereomers of (+)-3‚-bromo-8- epicaparrapi oxide (de ) 20-25%) are produced in the enzyme reaction, whereas two diastereomers of these compounds are formed in the synthesis with 2,4,4,6-tetrabromocyclohexa-2,5-dienone (TBCO). V-BrPO likely functions by catalyzing the two-electron oxidation of bromide ion by hydrogen peroxide producing a bromonium ion or equivalent in the active site that brominates one face of the terminal olefin of nerolidol. These results establish V-BrPO's role in the biosynthesis of brominated cyclic sesquiterpene structures from marine red algae for the first time.

Hong Ming Shieh

Papers

Chiral, biomimetic total synthesis of (−)-aplysistatin