Lipase-Catalyzed Enantiomer Separation of 3-Hydroxy-4- (tosyloxy)butanenitrile:Synthesisof( R)-GABOB(¼ (3R)-4-Amino-3- hydroxybutanoicAcid)and( R)-CarnitineHydrochloride(¼ (2R)-3-Carboxy- 2-hydroxy-N,N,N-trimethylpropan-1-aminium Chloride) by AhmedKamal*, G.B.RameshKhanna, and TadiparthiKrishnaji Biotransformation Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India (phone: þ 914027193157; fax: þ 914027193189; e-mail: ahmedkamal@iict.res.in) Enzymatic resolution of racemic 3-hydroxy-4-(tosyloxy)butanenitrile (()-5) by using various lipases in different solvents were studied. The obtained optically pure (3R)-3-(acetyloxy)-4-(tosyloxy)- butanenitrile (( R)-6), upon treatment with aqueous ammonia followed by conc. HCl solution, provided ( R)-GABOB (¼ (3R)-4-amino-3-hydroxybutanoic acid; ( R)-1). Similarly, reaction of ( R)-6 with aqueous trimethylamine solution followed by conc. HCl solution provided ( R)-carnitine hydrochloride (¼ (2R)-3-carboxy-2-hydroxy-N,N,N-trimethylpropan-1-aminium chloride; ( R)-2 ·HCl) in an expedi- tious manner. Introduction. – g-Amino-b-hydroxybutanoic acid (GABOB; 1) is a compound of great pharmacological importance because of its biological function as a neuro- modulator in the mammalian central nervous system [1 – 6]. The ( R)-form of GABOB is shown to have greater biological activity than its ( S )-enantiomer [1b][7]. Moreover, the ( R)-isomer of GABOB serves as a precursor for ( R)-carnitine (( R)-2), a compound having a high level of medical significance. Carnitine is a vitamin-like substance and plays an important role in converting stored body fat into energy. Its primary physiological function is to transport long-chain fatty acids through the mitochondrial membrane [5a] [8] into the cellular compartments for oxidation where these fats can be converted into energy. Moreover, there are several medical indications for which carnitine has been prescribed [9] [10]. These include its usefulness as a pharmaceutical for hemodialysis [11] (hypolipidemic agent), heart diseases [9], and myopathic deficiencies [5a] [8e,f], etc. The discovery of the adverse effects of ( S )-carnitine [12] (( S )-2) and the questionable effectiveness of the racemic mixture in treating angina pectoris [13], coupled with the recent growing interest in therapeutic application of carnitine, has prompted its use in only the ( R)-form. The high biological importance associated with ( R)-GABOB (( R)-1) and ( R)-carnitine (( R)-2) continue to stimulate the interest of Helvetica Chimica Acta – Vol. 90 (2007) 1723 # 2007 Verlag Helvetica Chimica Acta AG, Zürich