Levulinic acid formation, mechanism

Horvat, J., Klaic, B., Metelko, B., and Sunjic, V, Mechanism of levulinic acid formation. Tetrahedron Lett 1985, 26 (17), 2111-2114. 

Pummerer R, Guyot O, Birkofer L (1935) Mechanism of levulinic acid formation from hexoses. II. A hydroxyl-free glucosan-like substance. Berichte 68B 480-493... 

The mechanism of the formation of levulinic acid probably involves the substance 5-hydroxymethylfurfural (XXVIII), which may also be obtained from sucrose by treatment with dilute oxalic acid. This... 

If water represents an attractive solvent for the conversion of carbohydrates, the formation of HMF in water is rather complex, mainly due to the possible rehydration of HMF yielding levulinic and formic acids (Scheme 6). The mechanism related to the rehydration of HMF was discussed first by Pummerer in 1935 [71] and then by Horvath et al. in 1985 [72]. Conversion of HMF to levulinic acid is... 

The analogous product from the pentose glycals and 2-deoxy-pentoses would be furfuryl alcohol, but, as it is unstable and is readily converted into levulinic acid under the conditions of formation, it is difficult to isolate. The spectral data52 and the fact that levulinic acid is the common product from 2-deoxy-D-erythro-pentose, D-ara-binal, and furfuryl alcohol19 substantiate the supposition that the mechanism is analogous to that just described. Other (unknown) products are formed in significant yield from the dehydration of 2-deoxy-D-ert/fhro-pentose.52,84 The mechanism of formation of levulinic acid is discussed in Section V (see p. 212). 

Levulinic Acid. Dehydration of glucose or other monomeric and polymeric C6 sugars leads to the direct formation of levulinic acid (LA) as a potential primary building block for the biorefinery, and several reviews have described its potential commercial utility 477,478 The preparation of levulinic acid is not difficult, although the mechanism of its formation from carbohydrates is complex, and offers several alternative decomposition pathways (equation 3).479... 

Levulinic Acid. Levulinic acid is formed by the acid catalyzed degradation of hexose sugars via the intermediacy of hydroxymethylfurfural (145). Although its formation was reported as early as 1836 (143), the mechanism of its formation has been studied at least as recently as 1985 (147). 

A wide range of carbohydrates is degraded by acids to furan compounds. For example, pentoses give 2-furaldehyde, and hexoses, 5-(hydroxymethyl)-2-furaldehyde (58), which may react further to yield levulinic acid. In 1910, Nef suggested the first mechanism, (55) to (58), for the formation of 5-(hydroxymethyl)-2-furaldehyde. His proposal was made at the end of his classical paper on the saccharinic acids, and was overlooked by subsequent workers and reviewers. In 1944, Haworth and Jones advanced an identical mechanism for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-fructose. 

Figure 2-3 The catalytic mechanism of ALAS as proposed by Jordan [66], The reaction mechanism involves the formation of a Schiff base linkage between glycine and the PLP cofactor. Removal of the pio-R proton yields a carbanion which reacts with the second substrate, succinyl-CoA. Note the retention of the pro-5 proton of glycine in the pro-5 position of C-5 of ALA. ALA, 5-amino-levulinic acid.

The mechanism of formation of levulinic acid from carbohydrates bears discussion. The subject was first taken up by Pummerer and co-workers in 1935 [166], who first recognized that HMF 1 was an intermediate which underwent rehydration to open chained products, but otherwise gave an oversimplified interpretation that involved the "dismutation" of oxygen from the CH2OH group in 66 to the terminal aldehyde (Scheme 21). 

The exact mechanism of action of the -amino levulinic acid synthetase is not clear. It involves the activation of glycine by pyridoxal phosphate in a Schiff base formation on the enzyme. A proton is lost in the process, and a stable carbanion is formed. In the presence of succinyl CoA, the activated glycine is transferred to succinate, but it is not clear whether the decarboxylation occurs while the succinate and glycine are still attached to the enzyme or later. The activity of the -amino levulinic acid synthetase is inhibited by L-penicillamine, thiosolidine, and L-cysteine. The compounds presumably react with pyridoxal phosphate forming a thiazolidine ring. The enzyme molecule is itself inhibited by the addition of para-chloro-mercuri-benzoic acid. Insofar as succinate is a precursor of 5-amino levulinic acid, the pathway for succinyl CoA synthesis acquires particular significance (refer to the first part of this book). In the reticulocyte, the tricar-... 

Few alkaline hcf oxidations catalysed by OSO4 have been reported. The oxidation of L-valine (val) is zero order in hcf and a fractional order in val. The proposed mechanism assumes the formation of Os(VIII)-val eomplex. The oxidation of acrylic acid is zero order in hcf. The oxidation of chloramphenicol (chp) has an order less than unity in chp and OH ions. The oxidation of levulinic acid is also reported. ... 

Under elevated temperature conditions and acidic catalysis, hexoses eliminate 3 moles of water to form HMF (see [21] for possible reaction mechanisms). But in aqueous solution, reaction does not stop at this stage (Fig. 4). The dehydration reaction is subsequently followed by a rehydration step leading to levulinic and formic acid. In addition, this reaction sequence is accompanied by intermediates, side products, and at least the formation of colored soluble or insoluble polymeric compounds [23, 24]. 

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