Journal of Molecular Catalysis B: Enzymatic 21 (2003) 97–105 Microbial C-hydroxylation and -4-O-methylglucosidation of methyl-benzamide 7-azanorbornane ethers with Beauveria bassiana Horacio F. Olivo a,∗ , Tonya L. Peeples b , Mar´ ıa-Yolanda R´ ıos a , Francisco Velázquez a , Jin-Woo Kim b , Someet Narang b a Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA b Department of Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA 52242, USA Received 13 May 2002; accepted 3 July 2002 Abstract N-Substituted 7-azanorbornanes were prepared by acylation of easily accessible 7-azanorbornane hydrochloride. Deriva- tives possessing an electron-withdrawing docking/protecting group and bearing an aryl methylether were subjected to bio- transformation with the fungus Beauveria bassiana ATCC 7159. O-Demethylation and -4-O-methylglucosidation reactions were observed for the major metabolite in this biotransformation (isolation yields: 6, 30%; 11a, 44%; 11b, 47%; 11c, 14%). C-Hydroxylation on an unfunctionalized carbon was also observed in most of the cases. © 2003 Elsevier Science B.V. All rights reserved. Keywords: 7-Azanorbornanes; C-Hydroxylation; O-Demethylation; -4-O-Methylglucosidation; Beauveria bassiana 1. Introduction The use of selected microorganisms in the bio- transformation of xenobiotics to effectively mimic the mammalian metabolism of drugs and natural products was introduced by Rosazza and Smith [1]. Micro- bial transformations have also proved valuable in obtaining good amounts of metabolites in a practical fashion [2]. The use of microbial transformations for the preparation of key synthetic intermediates has be- come a powerful technique that is particularly useful for the synthesis of valuable compounds that other- wise would take more efforts to synthesize. The fila- mentous fungus Beauveria bassiana ATCC 7159 has ∗ Corresponding author. E-mail address: horacio-olivo@uiowa.edu (H.F. Olivo). become a very popular microorganism among syn- thetic organic chemists because of its wide variety of substrate specificity and wide spectrum of activity [3]. We recently reported the microbial hydroxylation of an unfunctionalized carbon, using B. bassiana, for the synthesis of an important intermediate in the total synthesis of the natural alkaloid epibatidine [4]. C-Hydroxylation occurred on a methylene carbon when an electron-withdrawing docking/protecting group was present on a 7-azanorbornane. The bio- transformation occurred with excellent stereocontrol in good to very good yields. However, the hydroxy- lation reaction showed poor enantioselectivity. We decided to explore the concept of a chiral auxiliary as a docking/protecting group in the biohydroxyla- tion of 7-azanorbornanes. This concept was applied recently by de Raadt et al. [5] in the biohydroxylation 1381-1177/03/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved. PII:S1381-1177(02)00081-4