Microbiologically produced carboxylic acids used as building blocks in organic synthesis.
Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.
Helmholtz-Centre for Environmental Research - UFZ, Permoserstr. 15, 04318, Leipzig, Germany.
Andreas
A
Aurich
Robert
R
Specht
Roland A
RA
Müller
Ulrich
U
Stottmeister
Venelina
V
Yovkova
Christina
C
Otto
Martina
M
Holz
Gerold
G
Barth
Philipp
P
Heretsch
Franziska A
FA
Thomas
Dieter
D
Sicker
Athanassios
A
Giannis
D002264:Carboxylic Acids / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D005942:Gluconates / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods; D008827:Microbiological Phenomena / Q000235:genetics; D025062:Yarrowia / Q000235:genetics / Q000378:metabolism
D002264:Carboxylic Acids; D005942:Gluconates; D007523:Isocitrates; D007656:Ketoglutaric Acids; C034219:isocitric acid; C030691:gluconic acid