Brevetoxin synthesis

Bartlett s research group has continued its work on the stereocontrol led synthesis of tetrahydrofurans and tetrahydropyrans, and has extended this work to the synthesis of polycyclic ethers as models for brevetoxin synthesis. Iodoetherification of the cyclohexanol (51) and subsequent rearrangement affords the tetrahydropyran (52), which in a subsequent iterative... 

A further signiHcant advance in Nicolaou s work on brevetoxin synthesis comes with the synthesis of the FGHU framework of brevetoxin A from 2-deoxy-D-ribose, D-glucal, and the known mannose-derived C-glycoside (65), as outlined in Scheme 14, the other chiral centres in (66) being derived from asymmetric epoxidation. O in model work on brevetoxin... 

Total synthesis of brevetoxin B, a fused polycyclic marine-derived saturated 0-heterocycle 97YGK686. 

The striking constitution of brevetoxin B, unprecedented at the time of its discovery in 1981, presents a formidable challenge to organic synthesis. The unique and fascinating molecular architecture of brevetoxin B (1), its association with the red tide catastrophes, its potent biological activity, and the prospects for expanding the arsenal of synthetic methods all contributed in roughly equal measure to our decision to pursue a total synthesis of 1. This chapter addresses the efforts that culminated in the total synthesis of brevetoxin B (1 ).6... 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

Final Stages and Completion of the Total Synthesis of Brevetoxin B... 

Only two operations remain. Reaction of the enolic form of aldehyde 162 with Eschenmoser s reagent (H2C=NMe2+I-)62 in the presence of triethylamine provides the desired enal after a simple / -elimination. Finally, cleavage of the remaining tcrt-butyldi-methylsilyl ether with HF pyridine completes the total synthesis of (+)-brevetoxin B (1). 

I11 Nicolaou s total synthesis of brevetoxin B, for example, out of the eleven transfused six- to eight-membered cyclic ethers, THP rings B, F, G, and I are constructed by application of this methodology through cydization of the appropriate... 

Scheme 35 Sequential formation of rings I and H by intramolecular allylation/RCM in Yamamoto s synthesis of the F-K ring segment 186 of brevetoxin B (184) [91]...

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

Prochiral aryl and dialkyl ketones are enantioselectively reduced to the corresponding alcohols using whole-cell bioconversions, or an Ir1 amino sulfide catalyst prepared in situ.695 Comparative studies show that the biocatalytic approach is the more suitable for enantioselective reduction of chloro-substituted ketones, whereas reduction of a,/ -unsaturated compounds is better achieved using the Ir1 catalyst. An important step in the total synthesis of brevetoxin B involves hydrogenation of an ester using [Ir(cod)(py) P(cy)3 ]PF6.696... 

M. L. Candenas, F. M. Pinto, C. G. Cintado, E. Q. Morales, I. Brouard, M. T. Diaz, M. Rico, E. Rodriguez, R. M. Rodriguez, R. Perez, R. L. Perez, and J. D. Martin, Synthesis and biological studies of flexible brevetoxin/ciguatoxin models with marked conformational preference, Tetrahedron, 58 (2002) 1921-1942. 

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