TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 3381–3385 Pergamon Stereoselective synthesis of (R )-(-)-denopamine, (R )-(-)-tembamide and (R )-(-)-aegeline via asymmetric reduction of azidoketones by Daucus carota in aqueous medium J. S. Yadav,* P. Thirupathi Reddy, S. Nanda and A. Bhaskar Rao Indian Institute of Chemical Technology, Hyderabad 500 007, India Received 8 December 2001; accepted 15 January 2002 Abstract—A simple and efficient stereoselective synthesis of (R )-denopamine and other naturally occurring hydroxy amides from optically active (R )-2-azido-1-arylethanols, is described for the first time via reduction of the corresponding -azidoarylketones with enzymes from Daucus Carota root, under mild and environmentally friendly conditions. The products are formed with high degrees of enantioselectivity. © 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction Many chiral -amino aryl ethanols are found to be potential synthetic precursors of pharmaceutically important molecules. 1 Recent studies have demon- strated that the two enantiomers of a chiral drug usu- ally display different biological activities 2 and in most of the aryl ethanolamine drugs, the biological activity resides mainly in the (R )-enantiomer. 3 The increasing demand and interest in the stereoselective synthesis of these biologically useful molecules prompted us to take up their synthesis. The synthesis of (R )-denopamine 1, a new selective -antagonist for the treatment of con- gestive heart failure 4 and other naturally occurring biologically active molecules such as (R )-tembamide 2 and (R )-aegeline 3, which are used in traditional Indian medicines and have been shown to have good hypo- glycemic activity, 5 has now been achieved. To date few methods have been reported for the synthe- sis of optically active (R )-denopamine 1, 6 (R )-tem- bamide 2 and (R )-aegeline 3, 7 these include either tedious chemical and biological methods 8 or require the use of expensive reagents with multi-step syntheses and low overall yields. 9 Recently, the asymmetric reduction of substituted -amino ketones to -amino alcohol derivatives 10 with high enantioselectivity using the Ru– BINAP complex has been reported. Our continuous investigations on the development of new environmentally favorable bioreduction processes for the synthesis of chiral azido alcohols, 11 which are potential intermediates for aryl ethanolamine drugs 12 and our keen interest in the utility of such strategies for the total synthesis of enantiopure pharmaceutically important molecules led us to complete the study reported herein. Recently, plant cell cultures 13 and whole plant cells 14 have been considered as suitable biochemical systems for the stereoselective reduction of prochiral ketones. More recently, we have investigated the reduction of a variety of prochiral ketones with Daucus carota root in aqueous medium provided the corresponding alcohols 15 with good to excellent enan- tioselectivity and in high yield. Accordingly, we have focused our attention to extend this methodology to the preparation of key intermediates, i.e. (R )-chiral azido alcohols 5a and 5b from the corresponding -azido aryl ketones 4a and 4b. * Corresponding author. Fax: +91-40-7160512; e-mail: yadav@iict.ap.nic.in 0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(02)00024-1