Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway?

We have shown for the first time that taxadiene ( 3 ) can be epoxidised in a regio- and diastereoselective manner to provide taxadiene-4(5)-epoxide ( 12 ) as a single diastereoisomer, and that this epoxide can be rearranged to give taxa-4(20),11(12)-dien-5α-ol ( 4 ). Furthermore, the epoxide 12 rearranges under acidic conditions to give taxa-4(20),11(12)-dien-5α-ol ( 4 ), the known bridged ether OCT ( 5 ) and the new oxacyclotaxane (OCT2) 15 . Contrary to previous speculation, taxadiene-4(5)-epoxide ( 12 ) is susceptible to rearrangement when exposed to an iron III porphyrin, and these observations justify consideration of epoxide 12 as a chemically competent intermediate on the taxol biosynthetic pathway. We report the first synthesis of taxadiene-4(5)-epoxide, which rearranges upon acid treatment to produce products of relevance to taxol biosynthesis.