Catalysis Today 198 (2012) 345–352 Contents lists available at SciVerse ScienceDirect Catalysis Today jou rn al h om epage: www.elsevier.com/locate/cattod Biocatalytic reduction of -keto amides to (R)--hydroxy amides using Candida parapsilosis ATCC 7330 Selvaraj Stella a , Anju Chadha a,b,∗ a Laboratory of Bioorganic Chemistry, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India b National Centre for Catalysis Research, Indian Institute of Technology Madras, Chennai 600036, India a r t i c l e i n f o Article history: Received 13 February 2012 Received in revised form 27 March 2012 Accepted 31 March 2012 Available online 27 May 2012 Keywords: Primary -keto amides Secondary -keto amides Biocatalytic reduction (R)--hydroxy amides Candida parapsilosis ATCC 7330 a b s t r a c t Biocatalytic reduction of primary and secondary -keto amides was accomplished using whole cells of Candida parapsilosis ATCC 7330. The primary (R)--hydroxy amides were obtained in good enantiomeric excess (up to 94%) and conversion (88–99%) as compared to the secondary (R)--hydroxy amides. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Optically active -hydroxy amides are important chiral inter- mediates for biologically active compounds like bradykinin B 1 selective antagonists or inverse agonists and chiral ligands for enantioselective addition reaction [1–4]. Asymmetric oxidation of racemic -hydroxy amides [5–7], ring opening of chiral ,-epoxy amides [8,9], enantioselective Passerini-type reaction [10] and asymmetric reduction of -keto amides [11,12] are the available chemical methods to prepare chiral -hydroxy amides. All these methods involve the use of expensive or toxic metal/chiral cata- lysts. Further, -keto amides bearing a chiral auxiliary are reduced using reducing agents like samarium iodide, borohydride, K- selectride to give the hydroxy amide in high diastereomeric excess [13–15]. Optically pure -hydroxy amides can also be synthesized from chiral -hydroxy esters [4] which in turn need to be syn- thesized by another asymmetric method. Biocatalysts are greener alternatives to chemical catalysts [16,17]. Biocatalytic prepara- tions of -hydroxy amides involve reduction of -keto amides [18–23], aminolysis of -hydroxy esters by lipases [24,25] and nitrile hydratase mediated hydration of optically active -hydroxy cyanohydrin [26]. The reported Candida antarctica lipase catalyzed aminolysis to prepare chiral -hydroxy amides involves the use ∗ Corresponding author. Tel.: +91 44 2257 4106; fax: +91 44 2257 4102. E-mail address: anjuc@iitm.ac.in (A. Chadha). of an optically active hydroxy ester which needs to be synthe- sized by another biocatalytic route in order to avoid the formation of racemic hydroxy amides [25]. For the hydration of cyanohy- drin, only a small number of enantioselective nitrile hydratases are known and the ee of the -hydroxy amides depends on the selec- tivity of oxy nitrilase enzyme which is used for the preparation of chiral cyanohydrin [27]. Hence, biocatalytic reduction of the prochi- ral precursor i.e. -keto amide is an efficient and straightforward method for the preparation of chiral -hydroxy amides. However, reported methods for the reduction of -keto amides are limited in contrast to the ubiquitous biocatalytic reduction of -keto esters, though amides and esters are similar groups. There are only few specific examples reported for the biocatalytic reduction of -keto amides. A purified carbonyl reductase from Candida parapsilosis IF0 0708 is known to reduce two cyclic keto amides, indoline-2,3- dione and its N-methyl derivative to (R)-hydroxy amide in 28% yield and >99% ee [18]. An -keto amide reducing enzyme from Saccha- romyces cerevisiae reduced chloro substituted benzoylformamides [19] and different actinomycete strains were used for the reduc- tion of 2-chlorobenzoylformamide to obtain both enantiomers of 2-chloromandelamide in >99% conversion and ee [20,21]. Catalytic antibodies reportedly reduced an -keto amide, (S)-3- (4-nitrophenyl)-2-oxo-N-(1-phenylethyl)propanamide, using the reductant NaBH 3 CN to give the product in >99% diastereomeric excess [22]. A complex keto amide was reduced using the cell free extract of Aerobasidium pullulans SC 13984 and glucose dehydro- genase in the presence of glucose and NADP with a maximum of 60% yield [23]. Given the fact that there is no general biocatalytic 0920-5861/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.cattod.2012.03.081