Oxepanes and Oxepines

The cyclic polyether neurotoxins, brevetoxins (BTXs) 40 and 41, isolated from cultured cells of the red tide organism Gymnodinium breve, are depolarizing substances that open the-voltage gated sodium (Na ) ion channels in cell walls [26]. 

The molecular stmcture of the BTXs consists of 10 or 11 ttansfused polycyclic rings (including five-, six-, seven-, eight-, and nine-membered oxacycles) fused in a linear array adorned by 22 tetrahedral stereocenters. 

BTX-A 40 (C49H70O13) consists of 5/8/6/7/9/8/8/6/676 ether rings trans-fused, and BTX-B 41 (C50H70O14) consists of 676/6/7/7/6/6/8/6/6/6 ether rings trans-fused. The structures of BTX-A and BTX-B were elucidated by X-ray crystallography [27,28]. 

Nakanishi and Shimizu have independently shown that most carbon atoms arise from a modified polyketide biosynthesis with some methyl groups from 5-adenosylmethionine or propionate [29, 30]. 

Labeling experiments using sodium [1- C]- and [2- C]acetate and [methyl- C]methionine demonstrated that the labeling patterns of 40 and 41 are similar. 

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Attempts to evaluate the synthetic potential of different preparative methods are made in Sections 13.02.7 and 13.02.8. In Tables 1-3, references are given to synthetic routes to several specific groups of oxepanes and oxepines. Most references are already cited in the previous sections. For completeness, see those from CHEC( 1984) and CHEC-II(1996). 

Table 1 Synthetic routes to monocyclic oxepanes and oxepines...

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