Synthesis from methyl 3- pyruvate

The vitamins K and other naphthoquinones arise from O-succinylbenzoate84 86 whose synthesis from chorismate and 2-oxoglutarate depends upon a thiamine diphosphate-bound intermediate, as indicated in Fig. 25-4. Elimination of pyruvate yields O-succinylbenzoate. The remaining reactions of decarboxylation, methylation, and prenylation (Fig. 25-4) resemble those of ubiquinone synthesis. 

Challenger and Liu (25) found that 3-methiolpropionate or 3-mercapto-pyruvate caused DMS formation by Scopulariopsis brevicaulis. Labarre and Bory (24) observed the conversion of 2-mercaptoacetate to a mixture of HjS and methanethiol by Clostridium oedematicus but mechanisms were not investigated probably a thiol S-methyltransferase catalyzes methanethiol synthesis from sulfide or via an S-methyl derivative of 2-mercaptoacetate. 

Further reports on asymmetric synthesis in the presence of Cinchona alkaloids have been made.142 " For example, hydrogenation of methyl pyruvate with a platinum-alumina catalyst containing quinine gives (+)-(/ )-methyl lactate in 87% optical yield.1426 Asymmetric induction with optical yields up to 36 and 26% has been observed in the Michael addition of thiols and nitro-alkanes to ct/ -unsaturated ketones in the presence of quaternary salts derived from the Cinchona alkaloids.142"... 

There are countless synthetic examples of the aldol condensation. In one example taken from Massanet s synthesis of eudesmanolides, diketone 134 was converted to the enolate anion with LDA. In a second step, methyl pyruvate was added to give a 98% yield of 135 and 136 in about a 1 1 ratio. 

In mammals, acetyl CoA from fatty acid oxidation cannot be used for the net synthesis of pyruvate or oxaloacetate, which in turn means that net glucose synthesis from acetyl CoA is impossible. However, glucose can be radioactively labeled when C-labeled acetate is introduced into human tissue culture cells and converted to acetyl CoA by acetyl CoA synthetase. Radioactive fatty acids can also be used to label glucose. Why If the methyl carbon of acetate is labeled, where will glucose be labeled ... 

Reduction of fluoroalkylpyrazines could be a promising method for the synthesis of chain-fluorinated piperazines. This method was used for the synthesis of difluoromethyl- and (l,l-difluoroethyl)piperazines 1283 nevertheless, it was obtained in low yield [322, 781], Therefore the synthesis of parent (trifluoro-methyl) piperazine 1284 is based on 4 steps synthesis started from methyl trifluoro-pyruvate and N,N -dibenzyl ethylenediamine (Scheme 287) [782]. 

This methodology was applied to the synthesis of L-streptose [91] and methyl a-D-mycaroside [95 a], The difficulty of this photochemical oxidation originates from the sensitivity of pyruvates to hydrolysis. This approach seems limited to small quantities of substrates but does not need any separation technique as in oxidation by pyridinium chlorochromate [95 b]. Nethertheless, photolysis of pyruvates of partially protected derivatives of a-D-g/ucofuranose and P-D-fructofuranose in benzene yields the corresponding oxidized products in excellent yields [96]. 

Fig. 11 Synthesis of (+)-(lfi,6S)-cw-8-oxabicyclo[4.3.0]nonan-7-one from cw-l,2-bis(hydroxy-methyl)cyclohexane catalyzed by HLADH. The cofactor NAD+ is regenerated by the system pyruvate/L-LDH...

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. 

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 1975, the Tumor Research Group of the Chinese Academy of Medical Science (47) reported a short synthesis of harringtonine (2) as shown in Scheme 19. Treatment of the olefinic pyruvate 148, obtained from the reaction of cephalotaxine and the corresponding acid, with mercuric tri-fluoroactate, followed by reduction with sodium borohydride yielded the known hemiketal 140. Reformatsky reaction of 140 with methyl bromo-acetate yielded harringtonine (2). 

---