Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1)

Journal article

A seven‐step synthesis of the first tricyclic intermediate in Danishefsky's total synthesis of eleutherobin is reported with Wittig homologation and sequential additions of metallated furan derivatives to aldehydes as key steps. Aiming to prepare hydroxylated eleutherobin analogues for cytotoxicity screening, the furan diol epimers 6 and precursors 1 and 2 were exposed to a 48‐member panel of engineered cytochrome P450BM3 variants. Both furan‐containing substrates reacted solely at the furan ring, one resulting in overall biocatalytic Achmatowicz reaction. Selective hydroxylation at four separate sp3 C–H centres was achieved in the substrates lacking the furan component. P450BM3‐catalysed hydroxylation of racemic substrates can proceed with kinetic resolution; in the case reported here, the 2°‐allylic alcohol product 10 was generated with an 82:18 enantiomeric ratio.

Authors: Syntrivanis, L; Wong, L; Robertson, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: European Journal of Organic Chemistry
• Volume: 45
• Pages: 6369-6378
• Publication date: 2018-09-19
• Acceptance date: 2018-09-19
• DOI: 10.1002/ejoc.201801206
• EISSN: 1099-0690
• ISSN: 1434-193X
• Keywords: C-H activation; eleutherobin; P450 enzymes