Synthetic Studies towards Medium Ring Oxacycles and Analogues: An Approach to the Synthesis of Chiral Tricyclic Nucleosides and Benzannulated Medium Ring Systems

Seven-membered oxacycles are structural units present in a wide variety of natural products1 including the monocyclic zoapatanol,2 the polycyclic hemibrevetoxin B,3 and more complex polyether toxins such as ciguatoxins and brevetoxins A and B.4 Numerous synthetic routes for functionalized oxepine heterocycles have been developed based on ring expansion,5 ring closing metathesis,6 palladium induced reactions,7 reductive intramolecular cyclization with SmI2,8 and several other methods.9 Interest in the use of the easily accessible carbohydrates from the chiral pool for the synthesis of optically active oxepine derivatives has been growing rapidly.10 In a continuation of our interest in the carbohydrate based synthesis of cis- and trans-fused tricyclic ethers,11 we felt that the use of the chiron approach along with the application of free radical reaction methodology offers a better and more convenient route for the synthesis of cis-fused tricyclic furobenzoxepine derivatives.12 The possibility of converting the intermediate furanose derivatives to nucleoside analogues was an added attraction. It should be mentioned that the design of conformationally restricted nucleosides as monomers in oligonucleotide analogues and as potent antiviral agents13 has attracted considerable attention recently