Enzyme-catalyzed C–C bond formation using 2-methyltetrahydrofuran (2-MTHF) as (co)solvent: efficient and bio-based alternative to DMSO and MTBE
Enzyme-catalyzed C–C bond formation using 2-methyltetrahydrofuran (2-MTHF) as (co)solvent: efficient and bio-based alternative to DMSO and MTBE
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DOI：
10.1039/c0gc00590h
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发表时间：
2010-12
期刊：
影响因子：
9.8
通讯作者：
S. Shanmuganathan;D. Natalia;Anne van den Wittenboer;Christina Kohlmann;L. Greiner;P. D. María
中科院分区：
文献类型：
--
作者：
S. Shanmuganathan;D. Natalia;Anne van den Wittenboer;Christina Kohlmann;L. Greiner;P. D. María
由苯甲醛裂解酶 (BAL) 催化的醛的酶促碳化反应（C-C 键形成）在水性介质中的温和反应条件下提供手性 α-羟基酮。为了提高水性条件下底物和产品的可用性，通常使用 DMSO 作为共溶剂或 MTBE 作为第二有机相来设置工艺。 DMSO 虽然高效，但会导致下游加工过程中的分离困难，并形成废水。 MTBE 提供了一种更清洁、更简单的后处理方法，但其石化来源及其较差的降解性引起了环境问题。据报道，2-甲基四氢呋喃 (2-MTHF) 是裂解酶催化反应中替代 DMSO 或 MTBE 的有前景的候选物。 2-MTHF 可以从生物基资源（例如乙酰丙酸）中提取，并且可以通过空气非生物降解。当 BAL 添加到 buffer-2-MTHF (5% v/v) 混合物中时，酶保持稳定，半衰期为 178 ± 8 h，生产率（安息香合成）为 10 g 安息香 L−1h−1。在这些条件下评估了几种 BAL 催化的醛碳联反应，在所有情况下均获得高分离产率（大多数为定量）和高对映选择性（高达 >99%）。此外，在 BAL 催化的安息香合成中使用两相系统获得的初步结果在 24 小时内提供了 60 g 安息香 L−1（ee > 99%）。因此，2-MTHF 可能是一种有价值的（共）溶剂，不仅可以解决环境问题，而且可以实现实用、高效的生物催化。
The enzymatic carboligation of aldehydes (C–C bond formation) catalyzed by benzaldehyde lyase (BAL) affords chiral α-hydroxy-ketones under mild reaction conditions in aqueous media. To enhance substrate and product availability under aqueous conditions, processes are often set-up using either DMSO as co-solvent, or MTBE as second organic phase. Although efficient, DMSO leads to difficulties in separation during downstream processing, with wastewater formation. MTBE provides a cleaner and straightforward work-up, but its petrochemical origin, together with its poor degradability, gives rise to environmental concerns. Herein it is reported that 2-methyltetrahydrofuran (2-MTHF) is a promising candidate to substitute DMSO or MTBE in lyase-catalyzed reactions. 2-MTHF can be derived from bio-based resources (e.g. levulinic acid), and it is abiotically degraded by air. When BAL is added to buffer-2-MTHF (5% v/v) mixtures, enzyme remains stable with a half-life of 178 ± 8 h, with productivities (benzoin synthesis) of 10 g benzoin L−1h−1. Several BAL-catalyzed aldehyde carboligations were assessed under those conditions, leading in all cases to high isolated yield (quantitative in majority), and to high enantioselectivity (up to >99%). Furthermore, preliminary results obtained with two phase systems in the BAL-catalyzed benzoin synthesis afforded 60 g benzoin L−1 in 24 h (ee > 99%). Therefore, 2-MTHF may be a valuable (co)solvent, not only to tackle environmental concerns, but also in terms of practical, efficient biocatalysis.