Pyruvic acid cyclic acetals

Some sugar residues in bacterial polysaccharides are etherified with lactic acid. The biosynthesis of these involves C)-alkylation, by reaction with enol-pyruvate phosphate, to an enol ether (34) of pyruvic acid, followed by reduction to the (R) or (5) form of the lactic acid ether (35). The enol ether may also react in a different manner, giving a cyclic acetal (36) of pyruvic acid. 

Cyclic acetals of pyruvic acid are common in extracellular polysaccharides (compare, for example, Ref. 6). They have also been found in some LPS, namely, those from Shigella dysenteriae type 6 and E. coli 0-149 (Ref. 139), and in the teichoic acid from Brevibacterium iodinum. The biosynthesis of these acetals has already been discussed. 

Acetalation. As polyhydroxy compounds, carbohydrates react with aldehydes and ketones to form cyclic acetals (1,13). Examples are the reaction of D-glucose with acetone and a protic or Lewis acid catalyst to form l,2 5,6-di-0-isopropylidene-a-D-glucofuranose [582-52-5] and its reaction with benzaldehyde to form 4,6-O-benzylidene-D-glucopyranose [25152-90-3]. The 4,6-0-(l-carboxyethylidine) group (related to pyruvic acid) occurs naturally in some polysaccharides. 

Similar enol ethers probably serve as intermediates in another common modification-reaction of monosaccharide units especially characteristic of exocellular polysaccharides, namely, the formation of cyclic acetals of pyruvic acid. 

The further metabolic changes undergone by shikimic acid are not yet clear. Mutants have been found that excrete two derivatives of shikimic acid (192). One of these, Zl, tentatively identified as a cyclic acetal of shikimic acid with pyruvic acid (192), may be a precursor of prephenic acid (191a). The other, Z2, is a phosphoshikimic acid, and possibly, but not yet certainly, is a normal metabolite succeeding shikimic acid in the chain. 

Some polysaccharides carry negative charges, by virtue of their uronic acid components and/or modification of OH groups as sulfate esters or cyclic acetals of pyruvic acid (CH3COCOOH) these can often be precipitated by cationic surfactants such as cetyltrimethylammonium bromide. They can also be fractionated on weak anion exchangers. For neutral polysaccharides, elaborate precipitation protocols involving initial removal of proteins and nucleic acids have to be used - a useful precipitant of the polysaccharide is 50% ethanol. 

Acetalization. Cyclic acetals of pyruvic acid are not easily prepared by using commonly available acetalization methods. Cyclic pyruvic acid acetals of carbohydrates were prepared by DMTST-promoted transacetalization reaction between methyl pyruvate diphenyl dithioacetal and carbohydrate... 

These considerations allow for a cyclic mechanism to occur in the formation of oxalic acid, where oxaloacetic acid yields either oxalate and acetate, which may be reoxidized, or pyruvate, which will then in turn yield acetate. This is illustrated in the following phase sequence of oxalate formation by these organisms ... 

One of the first persons to study the oxidation of organic compounds by animal tissues was T. Thunberg, who between 1911 and 1920 discovered about 40 organic compounds that could be oxidized by animal tissues. Salts of succinate, fumarate, malate, and citrate were oxidized the fastest. Well aware of Knoop s (3 oxidation theory, Thunberg proposed a cyclic mechanism for oxidation of acetate. Two molecules of this two-carbon compound were supposed to condense (with reduction) to succinate, which was then oxidized as in the citric acid cycle to oxaloacetate. The latter was decarboxylated to pyruvate, which was oxidatively decarboxylated to acetate to complete the cycle. One of the reactions essential for this cycle could not be verified experimentally. It is left to the reader to recognize which one. 

Since the formation of cyclic pyruvate acetals from alkyl pyruvates and diols under classical conditions (i.e. catalysis by acids) is expected to be unfavoured due to the necessity of the intermediate formation of a destabilized carbocation, early attempts to prepare 1-carboxyethylidene sugars used indirect procedures. Later, it was shown that under carefully controlled conditions the direct acetalation of a sugar diol with methyl pyruvate can also be used for preparative purposes. 

In the early 1900s, Thunberg proposed a cyclic pathway for the oxidation of acetate. In his scheme, two molecules of acetate are condensed, with reduction, to form succinate, which in turn is oxidized to yield oxaloacetate. The decarboxylation of oxaloacetate to pyruvate followed by the oxidative decarboxylation of pyruvate to acetate complete the cycle. Assuming that electron carriers like NAD" and FAD would be part of the scheme, compare the energy liberated by the Thunberg scheme with that liberated by the now-established citric acid cycle. Which of the steps in Thunberg s scheme was not found in subsequent studies ... 

Another hypothesis of aromatic amino acid synthesis, based on the distribution of the label in tyrosine of yeast grown on radioactive pyruvate or acetate, is that it involves the cyclic condensation of two unsym-metric 4-carbon acids, e.g., oxalacetate. The side chain of tyrosine appears to be formed from pyruvate as an intact 3-carbon unit. 

Gunsalus and Sagers (1958), in studying this sequence for C. acidiurici, propose that dissimilation of glycine proceeds either by condensation with FH4 and oxidation of the adduct, or else by way of serine to pyruvate and thence oxidative decarboxylation to acetate and COs. Formate and CO2 are in equilibrium, thus providing another cyclic mechanism for oxidation of Cl units. A similiar reaction sequence is stated to hold for the dissimilation of ycine by the anaerobe Diplococcua glyeinophilus. Glyoxylic acid is inert in these systems. 

---