Enzymatic Resolution of Biologically Active Precursors Versus Asymmetric Induction in Heterogeneous Catalysis

Abstract

Since the first isolation of the potent immunosuppressor FK 506 [1,2] (figure 1), many different approaches appeared in the literature for the synthesis of its cyclohexyl moiety. Some strategies, especially for the enantiomerically pure fragment are brilliant pieces of organic synthesis, although somewhat elaborate [3]. The average number of steps equals ten, some approaches using enantiopure educts. The classical way to such cyclohexyl fragments are Diels-Alder-Reactions [4]. Some of the more than twenty papers on the syntheses of structures like 3 use this methodology. To our knowledge, up to now, there is no report on the obviously most simple approach: hydrogenation of vanillic acid or derivatives thereof in order to obtain racemic products like 1. Inversion of configuration at C-4 by standard methods should provide the racemic compound 2, which easily can be separated from the undesired enantiomer by enzymatic resolution yielding enantiopure 3 [5] (scheme 1).