Oxidation enzyme-mediated asymmetric

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

The oxidation of heteroatoms and, in particular, the conversion of sulfides to asymmetric sulfoxides has continued to be a highly active field in biocatalysis. In particular, the diverse biotransformations at sulfur have received the majority of attention in the area of enzyme-mediated heteroatom oxidation. This is particularly due to the versatile applicability of sulfoxides as chiral auxiliaries in a variety of transformations coupled with facile protocols for the ultimate removal [187]. 

A successful case study for asymmetric nitrogen oxidation was reported for a series of (hetero)aromatic tertiary amines. High diastereoselectivity was observed for the enzyme-mediated oxidation of S-(—)-nicotine by isolated CHMOAdneto to give the corresponding ds-N-oxide [215]. The stereoselectivity of this biooxidation was complementary to the product obtained by flavin M O (FM O) from human li ver (trows-selective [216]) as well as unspecific oxidations by FMOs from porcine and guinea pig liver. 

Colonna S, Del Sordo S, Gaggero N, Carrea G, Pasta P (2002) Enzyme-Mediated Catalytic Asymmetric Oxidations. Heteroatom Chem 13 467... 

Colonna, S., Del Sordo, S., Gaggero, N., Carrea, G. and Pasta, P. (2002) Enzyme-mediated catalytic asymmetric oxidations. Heteroatom Chemistry, 13, 467 73. 

For the asymmetric reduction of ketone and aldehyde derivates, two electrochemical reduction systems using ADH as catalyst were examined (Fig. 22) [108]. In system A, the reduced coenzymes are regenerated using either FNR for NADPH or DP for NADH. Methyl viologen serves as electron mediator between the electrode and FNR/DP. System B contains ADH as sole enzyme, which catalyzes both reduction of substrates and regeneration of cofactors. Phenylethanol is oxidized by ADH accompanied by reduction of NADP+ to NADPH and its oxidation product acetophenone is reduced electrochemically at a glassy carbon cathode. 

Apart from the asymmetric metal catalysis, enantioselective Baeyer-Villiger oxidations mediated by enzymes have been known for some time [32,33,34]. Both whole-cell cultures and isolated enzymes, usually flavin-dependent monooxygenases, can be used to oxidize ketones enantioselectively. For future improvements in the asymmetric Baeyer-VilHger oxidation the use of chiral Lewis acids in combination with an appropriate oxidant seems worthy of intensive investigation. 

Epoxides are key chiral synthetic intermediates and their enantioselective preparation by oxidation of achiral alkenes is a key reaction in many synthetic strategies. Sharpless asymmetric epoxidation is suitable for most allylic alcohols [26, 27], but few general procedures exist for unfunctionalized olefins. Jacobsen s manganese salen-mediated epoxidation is suitable for and gives good selectivities with Z-olefins (85 to 90% ee) [28]. The enzyme chloroperoxidase... 

A comprehensive review (260 refs.) on the synthesis of carbohydrates from noncarbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni s thiazole and Vogel s naked sugar approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three Aldol Reaction Kits that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.). ... 

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