Bicyclic enzymic reduction

Carbonyl Reactivity.—A new reagent, lithium tri-s-butylborohydride, is claimed to exhibit enzyme-like stereoselectivity in reduction of cyclic (and bicyclic) ketones. Reduction of 2-methylcyclohexanone at 0°C in THF for 30 min occurred quantitatively to give the less stable cis-alcohol with an epimeric purity of 99.3%. 3,3,5-Trimethylcyclohexanone was reduced to the trans-alcohol with 99.8% stereoselectivity and 3-methylcyclohexanone likewise with 85% stereoselectivity. Reduction of 4-methylcyclohexanone to the cis-alcohol occurs with 80.5% stereoselectivity correspondingly cis-4-t-butyl-cyclohexanol is produced with 93% isomeric purity, much higher than in previous cited procedures, and this figure rises to 96.5% when reaction is... 

As seen above with the phosphate receptors, researchers are often not satisfied with only binding their targets, but they also want to mimic enzymes and produce some catalytic activity from their receptors. De Mendoza and collaborators used the bicyclic guanidinium 47 to effect the addition of pyrrolidine to a,p unsaturated lactones [79]. Using a 10% catalyst loading in chloroform, an eightfold reduction in the half-life of the starting materials was observed by... 

Reductions of symmetrical bicyclic diketones may also be effected selectively, as illustrated in Scheme 12. The stereospecificities of the HLADH-catalyzed transformations of the unsaturated decalin-diones (25) and (27) to the corresponding hydroxy ketones (26) and (28), and in fact all specificity aspects of this enzyme, are fully predictable using a simple to use, cubic-space model of the enzyme s... 

Enantiomeric and diastereotopic face specific reductions are also readily effected on racemic bicyclic ketones. An illustration of the broad structural range that is amenable to enzyme-catalyzed transformation in this way is given in Scheme 38. While 2-decalones, such as ( )-(81)- 83), and the related heterocyclic analogs ( )-(85) are good substrates for HLADH, the 1-decalone ( )-(84) is not. However, by changing enzymes to MJADH, ( )-(84) becomes a good substrate.Similarly, TBADH is a highly satisfactory catalyst for stereospecific reduction of ( )-(86), but will not accept its dimethyl... 

The second step of the penicillin and cephalosporin biosynthesis is the cycliza-tion of the linear ACV tripeptide to the bicyclic IPN, catalyzed by IPNS (cyclase), a nonheme-Fe(II)-dependent oxidase. The enzyme has a molecular mass of about 38 kDa and formally catalyzes a reaction which is exceptional in that a densely functionalized bicyclic ring is formed in a single four-electron oxidation step from a simple tripeptide through the removal of four hydrogen equivalents of the ACV tripeptide in a desaturative ring closure with concomitant reduction of dioxygen to water [162]. 

Horse liver ADH is a very universal enzyme with a broad substrate specificity and excellent stereoselectivity. Historically, it is the most widely used dehydrogenase in biotransformations [775, 776]. The three-dimensional structure has been elucidated by X-ray diffraction [778]. Although the primary sequence is quite different, the tertiary structure of HLADH is similar to that of YADH [779]. The most useful applications of HLADH are found in the reduction of medium-ring monocyclic ketones (four- to nine-membered ring systems) and bicyclic ketones [780-782]. Sterically demanding molecules which are larger than decalines are not readily accepted and acyclic ketones are usually reduced with modest enantioselec-tivities [783, 784]. 

Hydroxysteroid dehydrogenases (HSDH) are ideally suited enzymes for the reduction of bulky mono- [823] and bicyclic ketones (Scheme 2.121) [824]. This is not surprising if one thinks of the steric requirements of their natural substrates steroids [825, 826]. 

Fogal, E., Forzato, C., Nitti, P., Pitacco, G., and Valentin, E. (2000) Synthesis of enantiomerically pure bicyclic condensed [delta]-lactones via microbial reduction and enzymic resolution strategies. Tetrahedron Asymmetry, 11 (12), 2599-2614. 

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