Switching from S- to R-Selectivity in the Candida antarctica Lipase B-Catalyzed Ring-Opening of ω-Methylated Lactones:  Tuning Polymerizations by Ring Size

• Published in: Journal of the American Chemical Society 2007-06, Vol.129 (23), p.7393-7398
• Main Authors: van Buijtenen, Jeroen, van As, Bart A. C, Verbruggen, Marloes, Roumen, Luc, Vekemans, Jef A. J. M, Pieterse, Koen, Hilbers, Peter A. J, Hulshof, Lumbertus A, Palmans, Anja R. A, Meijer, E. W
• Format: Article
• Language: English
• Subjects: Binding Sites; Catalysis; Computer Simulation; Fungal Proteins - chemistry; Lactones - chemistry; Lipase - chemistry; Methylation; Models, Molecular; Molecular Conformation; Polymers - chemistry; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja071241a

Novozym 435-catalyzed ring-opening of a range of ω-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes ≤7) to large lactones (ring sizes ≥8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).