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

Naomi A Barton; Benjamin J Marsh; William Lewis; Nathalie Narraidoo; Graham B Seymour; Rupert Fray; Christopher J Hayes

doi:10.1039/c5sc03463a

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

Chem Sci. 2016 May 1;7(5):3102-3107. doi: 10.1039/c5sc03463a. Epub 2016 Jan 26.

Authors

Naomi A Barton¹, Benjamin J Marsh¹, William Lewis¹, Nathalie Narraidoo², Graham B Seymour², Rupert Fray², Christopher J Hayes¹

Affiliations

¹ School of Chemistry , University of Nottingham , University Park , NG7 2RD , Nottingham , UK.
² Division of Plant and Crop Sciences , School of Biosciences , University of Nottingham , Sutton Bonnington , LE12 5RD , Loughborough , UK . Email: chris.hayes@nottingham.ac.uk ; ; Tel: +44 (0)115 951 3045.

Abstract

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.