Carboxylic acids microbial synthesis

Dihydro-2//-pyrido[l,2-n]pyrimidin-2-one was used in the synthesis of antiallergic tricyclic triazolobenzazepine derivatives (99MIP3). 8-[2-(4-f-Propyl-2-thienyl)ethenyl]- and 8-[(4-/-propryl-2-thienyl)methoxy]-4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxylic acids were patented for the treatment of preventing and/or treating microbial infectious diseases (OlMIPl). 

The ease of the Strecker synthesis from aldehydes makes a-aminonitriles an attractive and important route to a-amino acids. Fortunately, the microbial world offers a number of enzymes for carrying out the necessary conversions, some of them highly stereoselective. Nitrilases catalyze a direct conversion of nitrile into carboxylic acid (Equation (11)), whereas nitrile hydratases catalyze formation of the amide, which can then be hydrolyzed to the carboxylic acid in a second step (Equation (12)). In a recent survey, with a view to bioremediation and synthesis, Brady et al have surveyed the ability of a wide range of bacteria and yeasts to grow on diverse nitriles and amides as sole nitrogen source. This provides a rich source of information on enzymes for future application. 

Microbially produced (2.S .3.S )-// .v-dihvdroxy-2.3-dihvdrobenzoic acid was used in the synthesis of enf-streptol, enf-senepoxide, and /so-crotepoxide (Fig. 33). The short and efficient synthesis of these biologically active compounds included the esterification of the carboxylic acid and protection of the diol moiety, delivering control of the regio- and stereoselectivity of the following epoxidation or dihydrox-ylation steps [178, 180]. 

Increasing interest has been directed to the microbial synthesis of chiral compounds that would not be readily accessible by chemical synthesis, and a few examples are given to illustrate the diversity of reactions that have been examined the stereoselective hydrolysis of nitriles to carboxylic acids has already been noted. Both by microbiological reactions and by combinations of microbiological transformation of aromatic compounds followed by designed chemical transformation (see Chapter 4, Section 4.2.3) have been used. Illustrations of both will be given. 

K. and Ohta H., Microbial deracemization of a-substituted carboxylic acids control of the reaction path. Tetrahedron Asymmetry, 2004, 15, 2965-2973 (h) Kato, D., Mitsuda S. and Ohta, H., Microbial deracemization of a-substituted carboxylic acids substrate specificity and mechanistic investigation, /. Org. Chem., 2003, 68, 7234-7242 (i) Mitsukura, K., Yoshida, T. and Nagasawa T., Synthesis of (R)-2-phenylpropanoic acid from its racemate through an isomerase-involving reaction by Nocardia diaphanozonaria, Biotechnol Lett., 2002, 24, 1615-1621. 

Very recently, lactones have received increasing attention as potential renewable platform chemicals. Perhaps the most prominent bio-based hydroxy fatty acids lactic acid, whose cyclic ester of two lactate molecules serves precursor for the synthesis of bio-based polymers. Fermentative production of hydroxyl-carboxylic acids from agro-industrial waste is an alternative to the synthesis from dwindling fossil resources (Fiichtenbusch et al. 2000). The enzymatic machinery for the production of polyhydroxyalkanoates (PHA) in bacteria offers catalytic pathways for the production of these lactone precursors (Efe et al. 2008). Recent examples include the microbial synthesis of y-butyrolactone and y-valerolactone. Particularly y-valerolactone is of importance and ranks among the top key components of the biomass-based economy. Microbial processes thus offer the perspective of a sustainable fermentative production of optically pure renewable lactones. 

The de novo synthesis of fatty acids in the mammary gland utilizes mainly acetate and some (3-hydroxybutyrate. These precursors arise from the microbial fermentation of cellulose and related materials in the rumen. Once in the mammary gland, acetate is activated to acetyl-CoA. The mechanism of fatty acid synthesis essentially involves the carboxylation of acetyl-CoA to malonyl-CoA, which is then used in a step-wise chain elongation process. This leads to a series of short-chain and medium-chain length fatty acids, which differ by two CH2 groups (e.g., 4 0, 6 0, 8 0, etc.) (Hawke and Taylor, 1995). These are straight-chain, even-numbered carbon fatty acids. However, if a precursor such as propionate, valerate or isobutyrate, rather than acetate, is used, branched-chain or odd-numbered carbon fatty acids are synthesised (Jenkins, 1993 see Chapter 2). 

Amino acids are organic compounds having one or more amino groups and carboxylic groups and are the basic biomolecules of proteins. Amino acids find applications in food and feed, pharmaceutical, and cosmetic industries. Even though amino acids can be produced by enzymatic synthesis, chemical synthesis, and as protein hydrolysate extracts, microbial fermentation has been the most favored means of production. The development of fermentation process assured the production of biologically active L-form of the... 

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