Pyruvates, asymmetric reduction

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

The reagent is also useful for asymmetric reduction of a-keto esters, particularly a-keto /-butyl esters. Thus /-butyl pyruvate is reduced to (S)-/-butyl lactate in 100% ee.1... 

Asymmetric reduction of a-keto esters. / lkyl pyruvates are rapidly reduced by this borane to alkyl (S)-lactates (equation I). The jxtent of asymmetric induction depends to some extent on the temperature and the size if the ester group. Quantitative optical... 

The formation of /3-carbolines in vivo can be enhanced by injecting rats intraventricularly with tryptamine and pyruvic acid to produce significant brain levels of the 1-carboxylic acid TBC 38 (84). Injection of TBC 38 into rats resulted in the formation of DBC 34, TBC 29a, and BC 36 as the major metabolites (85). It was suggested that DBC 34 resulted from TBC 38 by oxidative decarboxylation and that TBC 29a was formed from DBC 34 by asymmetric reduction, with BC 36 occurring via further oxidation. The nonenzymatic decarboxylation of TBC 38 was greatly increased on addition of pydridoxal phosphate (86). The incubation of human platelets with tryptamine or serotonin afforded TBC 2S (87). These compounds were named tryptolines, which are identical with TBC, and were fully characterized by GC-MS techniques, and by comparison with synthetic standards and trifluoroacylated derivatives. 

No 3-carboxy-substituted TBCs, derived from L-tryptophan by the Pic-tet-Spengler route, have yet been isolated from mammalian tissues. The same is also true for the dicarboxylic acid 23a derived from the condensation of L-tryptophan with pyruvic acid (36). The 1-carboxy-substituted TBCs 37 and 38, on the other hand, occur in mammalian systems (70,71) and are metabolically decarboxylated (65,S5). Whether a direct enzymatic decarboxylation of racemic material, occurring with the (S) and (R) enantiomers at a different rate, could account for the formation of unequal amounts of the enantiomers of TBC has not been investigated so far. The pyruvic acid route to optically active TBC (Fig. 12) leading from TBC 38a to TBC 29a via DBC 34 is at tifie moment the preferred pathway (85,86,89), although the enzymes involved in the asymmetric reduction leading to TBC 29a and the hydroxylated metabolites TBCs 30a and 33a have been neither isolated nor characterized. 

Do optically active 1-methyl-TIQs, as sketched in Fig. 32 for the synthesis of (7 )-salsolinol, originate from a Pictet-Spengler reaction of dopamine with acetaldehyde derive from ethanol, or are they the result of a Pictet-Spengler reaction of biogenic amines with pyruvic acid, as sketched in Fig. 33 Based on the accumulated data it seems reasonable to propose that optically active TIQs are formed by the pyruvic acid pathway, and that the pyruvic acids may be derived from an impaired glucose metabolism or an impaired amino acid metabolism. Whether the intermediate TIQ-1-carboxylic acids 91a,b are enzymatically decarboxylated to afford 64a,b in a different enantiomeric ratio, or whether optically active TIQs are formed by oxidative decarboxylation of TIQ 91 to DIQ 120, followed by an asymmetric reduction, remains open to question. 

Asymmetric reduction of a-keto esters, typically pyruvates and phenylglyoxylates, is effected by chiral rhodium complex-catalyzed hydrosilylation . Optical yields of lactates are higher than those obtained for simple prochiral ketones. The ester group as well as the hydrosilane used effects the extent of asymmetric induction. A high optical yield is attained for M-propyl pyruvate using a-naphthylphenylsilane (85.4% e.e.p ... 

Double asymmetric reduction of (-)menthyl pyruvate and (-)menthyl phenyl-glyoxylate uses rhodium(I) complexes with (-I-)DIOP or ( —)DIOP as cataJysP . Although only a slight effect of (— )menthyl group on the asymmetric induction is observed in the case of (— )menthyl pyruvate, i.e., (+ )DIOP, 85.6% d.e., S (— )DIOP, 82.8%... 

Fortunately, a host of methods is available for achieving this goal. They include resolution of a D,L-mixture [238] inversion of L-lactic acid derivatives (see Sections 1.2.1.2 and 1.2.2.2) asymmetric reduction of pyruvates catalytically [239], enzymatically [240], or with chiral boranes [241] and diazotization of D-alanine derivatives, which proceeds with net retention of configuration [242,243]. In addition, D-lactic acid can be obtained by the fermentation of glucose with Lactobacillus leichmannii in the presence of calcium carbonate [244],... 

K. Takahashi, H. Yokomizo, K. Ishiyama, M. Kitsuta, M. Ohashi, New aspects of cyclodextrin chemistry induced by outside type complex formation asymmetric reduction of indol-3-pyruvic acid with NaBH4, J. Incl. Phenom. Macrocyc. Chem., 2006, 56, 95-99. 

Catalytic hydrogenation of a-keto-esters can be achieved in the presence of homogeneous neutral Rh complexes of the Wilkinson type. Asymmetric reduction occurs when chiral bis-phosphines are employed as ligands, and one of the best optical yields known for homogeneous a-keto-ester hydrogenation (76%) is observed with (20a) as a ligand and propyl pyruvate as substrate. Use of the ligand (20b) increases the lipophilicity of such rhodium catalysts, and hence their solubility in non-polar solvents. ... 

The asymmetric reduction of a-keto esters, typically w-propyl pyruvate and ethyl benzoylformate, has been achieved [55] under conditions of chiral rhodium complex-catalyzed hydrosilylation as shown in equation (21). 

CATALYTIC ASYMMETRIC REDUCTION via HYDROSILYLATION OF ALKYL PYRUVATES AND ETHYL BENZOYLFORMATE [55]... 

DOUBLE ASYMMETRIC REDUCTION OF (-FMENTHYL PYRUVATE AND (-)-MENTHYL BENZOYLFORMATE... 

Thus, (—)-menthyl pyruvate was hydrosilylated using rhodium complexes with (/ )-BMPP, (-l-)-DIOP or (—)-DIOP as chiral phosphine ligand, giving a lactic acid derivative, equation (22). The results of this double asymmetric induction are listed in Table 16. The optical 3delds attained by the system are rather low as compared with those obtained in case of the asymmetric reduction of -propyl pyruvate (cf. Table 15). Thus, the effect of (—)-menthyl group is by no means remarkable in these cases. 

At almost the same time, MacMillan and coworkers found that the reductive amination starting from aldehyde, amine, and Hantzsch ester 39 also proceeded smoothly by means of 1 in the presence of 5 A MS to afford benzylic amines 43 with 83-97% ee (Scheme 11.11) [22]. They proved that dialkyl ketones as well as alkyl aryl ketones were suitable substrates even methyl ethyl ketone was reduc-tively aminated with 83% ee. They also reported the asymmetric reduction of pyruvic-acid-derived cyclic imino ester 44. In this reaction, the structure of 44 exhibited a remarkable correlation to MM3 calculations in terms of both hydrogen bond orientation and specific architectural elements that dictate iminium enan-tiofacial discrimination. 

Rev. 42 (2013) 6213-6222. (d) L. Cao, F.v. Rantwijk, R.A. Sheldon, Cross-linked enzyme aggregates a simple and effective method for the immobilization of penicillin acylase, Org. Lett. 2 (2000) 1361-1364. (e) T. Matsuda, K. Nakayama, T. Abe, M. Mukouyama, Stabilization of pyruvate decarboxylase under pressurized carbon dioxide and water biphasic system, Biocatal. Bio-trans. 28 (2010) 167-171. (f)T. Matsuda, R. Marukado, M. Mukouyama, . Harada, K. Nakamura, Asymmetric reduction of ketones by Geotrichum candidum immobilization and application to reactions using supercritical carbon dioxide. Tetrahedron Asymm. 19 (2008) 2272-2275. 

Synthesis of t-ferf-leucine via asymmetric reductive amina-tion of tri methyl pyruvic acid with a recombinant whole-cell catalyst containing a leucine dehydrogenase and a formate dehydrogenase. 

The reaction of optically active carbinolamines formed by an enzymatically controlled addition of acetaldehyde to amines, illustrated in Fig. 2, may be of theoretical interest, but lacks experimental verification it also would require the presence of acetaldehyde. The more likely pyruvic acid route to optically active TIQs, however, also remains inconclusive. If it indeed proceeds through TIQ-1-carboxylic acids to DIQ intermediates by an oxidative decarboxylation (176,217,218), it requires that it be followed by an asymmetric enzymatic reduction. Although achieved in vitro (35), this reaction has not been realized in vivo. The formation of unequal amounts of the optical isomers of salsolinol and other TIQs in vivo could arise from racemic 1-carboxy-TIQ in an enzymatic decarboxylation, proceeding with (S) and (R) enantiomers at a different rate and thus affording different amounts of (5)- and (/ )-TIQ. With the availability of optically active TIQ-1-carboxylic acids, this possibility can now be tested. 

In addition to four component condensation, several other applications of chiral primary ferrocenylalkyl amines have been published. Thus, an asymmetric synthesis of alanine was developed (Fig. 4-3la), which forms an imine from 1-ferrocenylethyl amine and pyruvic acid, followed by catalytic reduction (Pd/C) to the amine. Cleavage of the auxiliary occurs readily by 2-mercaptoacetic acid, giving alanine in 61% ee and allowing for recycling of the chiral auxiliary from the sulfur derivative by the HgClj technique [165]. Enantioselective reduction of imines is not limited to pyruvic acid, but has recently also been applied to the imine with acetophenone, although the diastereoisomeric ferrocenylalkyl derivatives of phenylethylamine were obtained only in a ratio of about 2 1 (Fig. 4-31 b). The enantioselective addition of methyl lithium to the imine with benzaldehyde was of the same low selectivity [57]. Recycling of the chiral auxiliary was possible by treatment of the secondary amines with acetic acid/formaldehyde mixture that cleaved the phenylethylamine from the cation and substituted it for acetate. 

In contrast to asymmetric hydrogenation, examples of stereoselective reduction of functionalized ketones are rare. Scheme 43 illustrates the highly enantioselec-tive reduction of methyl benzoylformate in 2-propanol containing KOH using a catalyst prepared in situ from [RhCl(CgHjo)]2 and (S,S)-3 [101]. With the same catalyst, methyl pyruvate is reduced in 5% optical yield. 

The new mannitol-based diphosphinite ligands 233 (R = Ph, cyclopentyl, cyclohexyl) have been prepared, and used in rhodium complexes for the asymmetric hydrogenation of prochiral ketones. The cases where R = cyclohexyl gave highest enantioselectivity, up to 86% for the reduction of methyl pyruvate to give methyl R-lactate. °... 

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