Science of Synthesis

Li, A. T.; Li, Z., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 2, 495.

Recently, protein engineering and directed evolution have been applied to create P450 enzyme mutants with improved enzyme activity and enantioselectivity. Several P450BM3 mutants have been obtained that produce the R-epoxides with significantly improved enantioselectivity. For instance, epoxidation of styrene (‌20‌, Ar1 = Ph) and 3-chlorostyrene (‌20‌, Ar1 = 3-ClC6H4) with the P450 BM3-F87G (Phe87Gly) mutant gives the corresponding R-epoxides ‌21‌ in 92 (Ar1 = Ph) and 94.6% (Ar1 = 3-ClC6H4) enantiomeric excess, respectively (‌Scheme 11‌).[‌99‌,‌100‌]

Meeeeeeee, M888eee eeee Meeeeeeeeeee ee. MMM-888 eee eeee eeee eeeeeeeeee eee eee M888eeeMM eeeeee eeeeeeeeeeee eeeeeee eeeeeeee M eeeeeeeeeeeeeeeeee eee eee eeeeeeeeeee ee eeee 8-eeeeeeeeeee eeeeeeee ‌88‌ eeeeeeeeee eeeeeeee-eeeeeeeeeee eeeeee (M8 = MM8, MM8, MM) ee eeee eee eeeeeeeeeeeee M-eeeeeeee ‌88‌ ee 88–88% ee.[‌88‌] Mee eeee M eeeeeeeeeeeeeeeeee eeeeeeee ee eee M888 eeeeeeeee eeeeeeeeeee eeeeeeeeeee eee eeeeeee eeeeeeeeeeeee eeeeeeeee eeeeeeeee eeee, ee eeeee eeee eee M-eeeeeeee eee eeeeee eee ee eeeeeeee ee eeeee eee eee eeeeeeeeee eeeeeeeeee eeeeeeee-eeeeeeeeeee eeeeee. Meeeeeee, eee M888eeeMM eeeeee eeeee eeeeeeee M eeeeeeeeeeeeeeeeee eee eee eeeeeeeeeee ee eeeeeee 8-eeeeeeeeeee eeeeeeee ‌88‌ ee eeee eee eeeeeeeeeeeee M-eeeeeeee ‌88‌ ee 88–88% ee.[‌88‌]

‌Meeeee 88‌ Meeeeeeeeee ee Meeeeee eee Meeeeeeeeee Meeeeeee eeee Meeeeeeeee Meeeeeeeee M888 Meeeeeeeeeeeee ee ee Meeeeee Meeee[‌88‌,‌88‌,‌888‌]

‌Meeeeeeeeee 88‌

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(M)-8-(8-Meeeeeeeeee)eeeeeee (‌88‌, Me8 = 8-MeM8M8); Meeeeee Meeeeeeee:[‌88‌]

Me e eeee eeeeeeeeee ee M. eeee (M888eeeMM, 888 eM, 88 e eeee eee eeeeee eee eeeee) eeee eeeee e 88% e/e eeee ee eeeeeee (888 µM, eeeee eeeeeeeeeeeee ee 8% e/e) eee 8-eeeeeeeeeeee (‌88‌, Me8 = 8-MeM8M8; 8 eM). Mee eeeeeeee eee eeeeeeeee ee 88 °M eee 888 eee ee e 888-eM eeeee eeee eeeee eee eee 8 e. Mee eeeeeee eee eeeeeeeeeee ee 8888e eee 88 eee ee eeeeee eee eeeee eee eee eeeeeeeeeee eee eeeeeeeee eeee ee eeeeeeeeee eeeeee ee MeMMe (8 × 888 eM). Mee eeeeeee eeeee eee eeeeeeeee, eeeeee eeee eee. ee MeMe, eee eeeee (Me8MM8) eeeeeeeee. Meeee eeeeeeeeee, eee eeeeeee eee eeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee/MeMMe 88:8, Me 8.8) ee eeee eee eeeeeee ee e eeeeeeeee eee; eeeee: 88.8%; 88.8% ee; [α]M88 −88.8 (e 8.8, MMMe8).

References