Keto fermentative synthesis

The ability to produce synthetic P-lactam antibiotics that have not come from fermentation is of considerable advantage industrially because microbiological spores are not present, negating the use of a dedicated contained plant. Evans and colleagues have described the synthesis of 1-carbacephalosporins (89), which are useful intermediates in the production of monocyclic P-lactam antibiotics.83 A significant step during this procedure is the conversion of an acylaminoazetidinone 90 to a P-keto ester 91 by ozonolysis (Scheme 11.24). 

There are many organic acids that can be produced by microbial or biochemical means. However, at present, only acetic acid (as vinegar), citric acid, itaconic acid, gluconic acid, 2-keto-gulonic acid, and lactic acid are produced industrially by fermentation. Other organic acids, such as fumaric, gallic, malic, and tartaric acids, once produced by fermentation or enzyme processes, are now produced commercially, predominantly by the more economic means of chemical synthesis. 

The alkyl esters of 3-hydroxybutanoic acid are a particularly useful group of compounds in organic synthesis because they are available in both chiral forms. Ethyl (5)-3-hydroxybutanoate, for example, may be prepared by the reduction of ethyl acetoacetate on the re side of the keto group with fermenting yeast and leads to an enantiomeric purity of about 85% which may be enriched further via a crystalline dinitrobenzoate. Synthesis of the R form was a little more difficult but could be achieved with 83-88% purity by the reduction of the acetoacetate with hydrogen in the presence of Raney nickel which had been treated with tartaric acid. " ... 

Synthesis of vitamin C (ascorbic acid) is conventionally performed via the Reichstein-Griissner procedure, which involves the fermentation of glucose followed by five chemical steps. Cerestar/ BASF recently developed a new process that consists of one fermentation step and two simple chemical steps (via 2-keto-L-gluconic acid). It is predicted that soon a fermentation process will be developed to convert glucose into vitamin C in a single step, eliminating several recovery steps and reducing extraction solvents. 

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