Fused polyether

The preparation of fused, polyether rings via RCM of enol ethers was reported by Rainier and co-workers <02T1997, 01TL179> (Scheme 38). The enol ether was prepared from the corresponding acetate using Takai s reduced-Ti protocol <94JOC2668>. Seven-membered, cyclic enol ethers could also be formed by this methodology. 

Two types of BTX have been characterised, designated type A and type B type A consists of a flexible spine of 10-fused polyether rings type B contains a rigid ladder of 11 rings. Additional analogues have been isolated from shellfish and these are postulated to be bioconversion products, the result of metabolism in the mollusc. In addition to the BTX, several phosphorous containing molecules were isolated from K. brevis that exhibit high ichthyotoxicity (Koley et al. 1995 Husain et al. 1996 Mazunder et al. 1997). 

Brevetoxins are methylated cyclic polyether toxins. There are two main types type A comprised of a flexible backbone of 10 fused polyether rings, and type B with a rigid backbone of 11 poly ether... 

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).

Shimizu/Nakanishi (24, 25) and 2) Gallimore and Spencer from all ( S,S)-trans epoxides (3). (d) Possible enzymatic routes to a fused polyether using 1) a mono-oxygenase and an epoxide hydrolase or 2) a monooxygenase only (3). 

Sasaki, M. et al.. New strategy for convergent synthesis of trans-fused polyether frameworks based on palladium-catalyzed Suzuki cross-couphng reaction. Tetrahedron Lett., 39, 9027, 1998. 

Along the Florida coast and in the Gulf of Mexico, the dinoflagellate Kare-nia brevis often forms blooms known as red tides that lead to massive flsh kills. The causative toxins, the brevetoxins, possess an unprecedented highly oxygenated structure. The brevetoxins were the first cyclic polyether compounds to be chemically identified, and were shown to possess a characteristic structural feature of a ladder-like skeleton consisting of trans-fused polyether rings. 

Usefiil designs in the synthesis of trans-fused polyether toxins. Alvarez, E., Candenas, M.L., Perez, R., Ravelo, J. L, Martin, J.D. (1995), Chem. Rev., 95, 1953-1980. Synthetic studies of biologically active marine cyclopeptides. Wipf, P. (1995), Chem. Rev., 95, 2115-2134. 

Clark, J.S., Grainger, DM., Ehkirch, A.A.-C., Blake, A.J., and Wilson, C. (2007) Synthesis of the fused polyether core of hemibrevetoxin B by two-directional ring-closing metathesis. Org. Lett, 9, 1033-1036. 

Fig. 21. Dendritic polyrotaxanes with mechanical branching units containing covalently linked bis-dendrons and a core imit fused to polyether macrocycles...

With Fused Pyridino Rings in Chiral Macrocyclic Polyethers. 270... 

In 1995, a report of human illness with diarrhetic shellfish poisoning (DSP)-like symptoms in the Netherlands was eventually found to result from the consumption of poisoned mussels (Mytilus edulis) harvested from Killary Harbour, Ireland (McMahon 1996). Yasumoto, Satake, and co-workers eventually isolated and proposed a stracture for the causative agent of this condition azaspiracid-1 (la. Fig. 16.1). The unique polyether stracture of azaspiracid-1 (la) is characterized by several spiro-cyclic systems, including an azaspiro ring fused to a 2,9-dioxabicyclo[3.3.1]nonane system and a terminal carboxylic acid. In total, there are nine rings and twenty stereogenic centers within the structure proposed by Yasumoto and co-workers in 1998 (Satake 1998). This stracture was based primarily on NMR spectroscopic data and did not include absolute stereochemistry, nor did it specify relative stereochemistry between the ABCDE and FGHI domains. 

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