Recent developments in biology, biochemistry and medicine have demonstrated that in most chiral compounds only one enantiomer is active. Subsequently, pharmaceutical and cosmetic industries, as well as food and agrochemical industries, have developed great interest in the stereoselective production of asymmetric compounds, as well as new systems that are able to perform it. Lisofylline (1-(5R-hydroxyhexyl)-3,7-dimethyl xanthine (LSF)), represents a new methylxanthine which is a stereospecific metabolite of pentoxifylline (1-(5-oxohexyl)-3,7-dimethyl xanthine (PTX)). LSF is an agent with anti-inflammatory properties, that was originally developed to reduce cellular damage due ischemic reperfusion, hypoxia or autoimmune diseases. Only the (R) stereoisomer is biologically active. As LSF is not commercially available in our country we had to obtain it by new methods [1,2]. In this study we reported biotransformation of PTX to LSF in the presence of whole cells of Lactobacillus kefiri (DMS 20587). These microorganisms possess NAD(P)H-dependent alcohol dehydrogenase (LKADH) (E.C.1.1.1.1.) which displays a broad substrate range and high stereoselectivity, therefore could convert prochiral ketone (PTX) by the asymmetric reduction to the chiral alcohol (LSF).

Lactobacillus kefiri DMS 20587 cells were grown in a MRS culture medium (pH 6, 30 ^oC, 48 h, under an atmosphere of nitrogen). Bioreductions were performed with resting cells of L. kefiri in 0.2 M potassium phosphate buffer (pH 6.5, 30 ^oC, 50 g_DCW/L). For the comparison co-substrates in 0.2 M potassium phosphate buffer with 5mM MgCl₂, with different concentracions of glucose (225, 450, 675 mM) and with different v/v concentacions of 2-propanol (2.5, 5, 10, 10%), respectively, were used. Yields of transformations and amounts of each enantiomer formation were examined by means of chiral HPLC.

The research was supported by Polish State Committee for Scientific Research (grant No 2 P05F 002 27)

[1]. Kieć-Kononowicz K., Pękala E. (CMUJ) Patent Application No. P-369904, 2004

[2]. Pękala E., Wójcik T. Joint Meeting on Medicinal Chemistry, Vienna, Sci.Pharm. Supp.1 73 (2), S67, 2005

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