Fused nine-membered ring system

Figure 2.1. Brevetoxins are based on two different structural backbones, based on what are perceived to be the two parent molecules, PbTx-2 (brevetoxin B) and PbTx-1 (brevetoxin A). All other known derivatives are based on alteration of the R-side chain, epoxidation across the double bond in the H-ring of PbTx-2, or derivatization at the C-37 hydroxyl in PbTx-2. PbTx-8, the chloromethyl ketone derivative of PbTx-2, is an artifact of chloroform extraction and subsequent phosgene conversion of PbTx-2. Common features include trans-fused polyether ring systems consisting of five- to nine-membered rings. denotes likely chemical artifact from extraction (Baden et al. 2005).

In the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I), the nine-membered Jt-excessive heterocycles, the heteronins, were surveyed up to 1982 (Chapter 5.20 of CHEC-I). This chapter covers developments of this class of heterocycle since that time, and also covers all other nine-membered rings containing nitrogen, oxygen and sulfur, including fused and bridged systems. 

The reductive ring opening of 5,6-fused ring systems has proved to be a valuable means of entry to nine-membered heterocycles. Leonard showed that bicyclic a-aminoketones (288) and (289) could be electrolyzed at a lead cathode to give octahydroazoninols (290) and (291) (Scheme 35) <52JA4620>. 

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