DOI: 10.1002/adsc.200505395 A One-Pot Enantioselective Chemo-Enzymatic Synthesis of Amino Acids in Water Chre´tien Simons, a, b Ulf Hanefeld, b Isabel W. C. E. Arends, a Thomas Maschmeyer, b, c Roger A. Sheldon a, * a Laboratory of Biocatalysis and Organic Chemistry, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands Fax: ( þ 31)-15-278-1415, e-mail: R.A.Sheldon@tudelft.nl b Laboratory for Applied Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands c Current address: Laboratory of Advanced Catalysis for Sustainability, School of Chemistry, University of Sydney, NSW 2006, Australia Received: June 7, 2005; Accepted: December 22, 2005 Abstract: The combination of immobilised Rh-Mono- Phos (1-AlTUD-1) and acylase I afforded a chemo- enzymatic, one-pot process for the enantioselective synthesis of amino acids in water, without the need for isolation of intermediates. In addition, the enzy- matic hydrolysis increases the enantiopurity of the product from 95% ee to > 98% ee. Compatibility studies revealed that for optimum results compart- mentalisation of the catalysts is required. Keywords: aminoacylase; asymmetric catalysis; cas- cade reaction; hydrogenation; immobilisation Introduction During the last decades an increasing urgency has arisen to develop greener and economically competitive proc- esses for the industrial synthesis of chemicals. [1] Espe- cially in the production of pharmaceuticals or agro- chemicals, where the waste generation can surpass 100 kg/kg product, this is a pressing necessity. [2] A very important tool in the chemist)s arsenal to achieve more environmentally benign processes is catalysis. Not only does the remarkable progress in (enantioselec- tive) chemocatalysis continue, but the potential of bio- catalysts is also increasingly being recognized by the fine chemical industry. [3] However, either of these cata- lysts only solve part of the problem, since they are usu- ally part of a complex multistep synthesis where the ma- jority of reaction steps still consist of classic stoichiomet- ric chemistry. Additionally, these processes usually re- quire wasteful and expensive isolation as well as purifi- cation of intermediates. For genuinely sustainable processes, the majority of the steps should be catalytic and, ideally, intermediate purification and isolation steps should be circumvented. Cascade reactions offer a unique opportunity to address these issues, in particu- lar when carefully orchestrated, involving enzymes and/ or chemocatalysts. [4–6] These two types of catalysts com- plement each other: transition metals are very versatile for oxidations and reductions (tasks often difficult to perform with enzymes, due to problems with cofactor re- generation) and enzymes readily perform hydrolytic re- actions and their reverse (whereas a chemo-catalytic ap- proach often requires drastic conditions and generates large amounts of salts as waste). To overcome the common incompatibility of reagents and conditions, smart solutions need to be found: immo- bilisation of the catalyst, as a form of compartmentalisa- tion or in combination with other compartmentalisation approaches, is often an efficient strategy. A noteworthy example was recently published by Gelman et al. [7] By immobilising a lipase and a rhodium complex in two sep- arate sol-gel matrices they were able to perform a one- pot esterification and hydrogenation reaction leading to saturated esters in good yields. In contrast, when only the enzyme was immobilised yields decreased al- most 7-fold. Thus, the support of the catalyst in this example has a similar function to a membrane in a cell – it inhibits the interaction of the incompatible re- agents. Recently, we reported in a communication the suc- cessful immobilisation of the asymmetric hydrogenation catalyst, Rh-MonoPhos, on AlTUD-1 ([1-AlTUD-1] Figure 1). [8] This catalyst is based on the synthetically readily accessible MonoPhos ligand, [9] which was immo- bilised via straightforward ionic interactions with the surface of the three-dimensional mesoporous material, AlTUD-1. [10] In this manner, the need for modification FULL PAPERS Adv. Synth. Catal. 2006, 348, 471 – 475 # 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 471