Chiral synthon with yeast

Enoate reductase reduces a,/3-unsaturated carboxylate ions in an NADPH-dependent reaction to saturated carboxylated anions. Useful chiral synthons can be conveniently prepared by the asymmetric reduction of a triply substituted C—C bond by the action of enoate reductase, when the double bond is activated with strongly polarizing groups [22]. Enoate reductases are not commercially available as isolated enzymes therefore, microorganisms such as baker s yeast or Clostridium sp. containing enoate reductase are used to carry out the reduction reaction. 

Similar carbohydrate-like chiral synthons are obtained by yeast reduction of the -acetoxyketones 58 and 59 ( ), bearing in 1,6 and 1,5 relationship, respectively, two masked carbonyl functions accessible chemoselectively with different reagents. The mode of reduction of 58 and 59 is, however, opposite. Whereas yeast treatment of 58 affords... 

During the pine saw-fly pheromone synthesis based on thiophilic addition it was shown that high enantio- and diastereoselectivity were observed in the reduction of p-ketodithioesters with baker s yeast, affording new and useful chiral synthons [346]. 

With the exception of the diol 9, that was obtained from the corresponding aldehyde in up to 35% yield, most of the chiral diols mentioned above were isolated in yields of only 20-25%. The formation of the acyloin-type condensation products is in competition with the much more efficient reduction of the carbonyl carbon and saturation of the double bond of the unsaturated aldehydes that were used as substrates. We became interested in the mode of reduction of particular aldehydes such as 54-56 (Scheme 8) in a study of the total synthesis of natural a-tocopherol (vitamin E) (23). We expected to obtain chiral alcohols that would be useful for conversion into natural isoprenoids from the reduction of the a-double bond of the above aldehydes. Indeed, 54-56 afforded up to 75% yield of the saturated carbinols 57-59 by treatment with yeast. Whereas the ee of 57 and 58 was ca 85%-90%, that of 59 is 99%, as shown by NMR experiments on the (-)-MTPA derivative (24). The synthetic significance of carbinol 59 was based on the structural unit present in natural isoprenoids (see brackets in structural formulas). This protected synthon can be unmasked by ozonolysis, as indicated by the high yield conversion of 59 into (S)-(-) -3-methyl-y-butyrolactone 60 (Scheme 9). Product 59 is a bifunctional chiral intermediate which does not need protective manipulation in that... 

Although most synthetic approaches to L-daunosamine start from carbohydrate precursors, some routes employ chiral synthons derived from other sources. The aldehydes 213 obtained through reaction of cinnamaldehyde with acetaldehyde in the presence of Baker s yeast followed by ozonolysis [157], and 214 obtained from L-tartaric acid [158-160] have been utilised in the synthesis of daunosamine derivatives, and protected daunosamines and acosamines have been synthesised from (synthetic approaches have employed lactic acid as a chiral starting material [162, 163] and the (S)-amine 215 obtained by resolution has been converted to V-benzoyl daunosamine together with its 3-epimer [164]. Wovkulich and Uskokovic have... 

At least two different oxidoreductases are found in yeast able to reduce 3-oxo esters with opposite sterochemical preferences [57]. The obtainment of homochiral 3-hydroxy estere is a relevant synthetic problem due to the value of this compound as a chiral synthon [2]. A number of structurally related 3-oxo esters of (5) absolute configuration (l series) can be obtained with yeast and other microorganisms under different conditions with high efficiency and high e.e. values. Simple structural variations permit change in stereoselectivity of the reduction [58-66]. 

Similarly, the two diastereoisomeric cyclic hydroxy esters can be obtained when baker s yeast or R. arrhizus is employed. The successful reduction of these racemic a-substituted (3-keto esters to a single enantiomer is based on the enolization/racemization of the keto esters, which allows a dynamic kinetic resolution. If coupled with the specificity of the enzymes from different microorganisms, this can lead to preparation of compounds of diverse chirality. Thus in the series of the 5- and 6-membered ring compounds (Scheme 18) both the lS,2R-cis- and the lS,2S-trans-hydroxy ester can be obtained by switching from baker s yeast to the biomass from R. arrhizus [97]. Such compounds are highly versatile chiral synthons that have been currently used in the asymmetrical synthesis of biologically active compounds [98]. 

A route to the key synthon (47 ,67 )-4-hydroxy-2,2,6-trimethylcyclo-hexanone had previously been developed by Leuenberger et al. 124) starting from the readily available isophorone. The chiral centre was introduced by enantioselective reduction with bakers yeast, and regio-selective reduction of one keto group was achieved by chemical reduction with nickel catalyst or by triisobutylaluminium under conditions where the desired trans diastereomer was the major product. 

Oishi T, Akita H 0983) Asymmetric reduction by yeasts. Formation of optically active synthons having two chiral centers useful for natural product synthesis. J Synth Org Chem Jpn 41 1031-1043 Okamoto T, Ohno A, Oka S (1977a) Reaction of N-propyl-1,4-dihydro-nicotinamide with ferricyanide ion. J Chem Soc Chem Commun 181-182 Okamoto T, Ohno A, Oka S (1977b) Alkali-metal ion acceleration of the electron-transfer reaction between N-propyl-1,4-dihydronicotinamide and ferricyanide ion. J Chem Soc Chem Commun 784-785 Okamoto T, Ohno A, Oka S (1979) Reduction of transition-metal salts by N-propyl-1,4-dihydronicotinamide. Bull Chem Soc Jpn 52 3745-3746 Ono N, Tamura R, Kaji A (1980) 1-Benzyl-1,4-dihydronicotinamide as a reagent for replacing aliphatic nitro groups by hydrogen An... 

Chiral (3-hydroxy esters are versatile synthons in organic synthesis specifically in the preparation of natural products [68-70]. The asymmetrical reduction of carbonyl compounds using baker s yeast has been demonstrated and reviewed [5,71,72]. In the stereoselective reduction of P-keto ester of 4-chloro- and 4-bromo-3-oxobutanoic acid, specifically 4-chloro-3-oxobutanoic acid methyl ester, Sih and Chen [73] demonstrated that the stereoselectivity of yeast-catalyzed reductions may be altered by manipulating the size of ester group using y-chloroacetoacetate as substrate. They also indicated that the e.e. of the alcohol produced depended on the concentration of the substrate used. Nakamura et al. [74] demonstrated the reduction of p-keto ester with baker s yeast and controlled... 

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