Microbial synthesis of (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester-a taxol side-chain synthon

Patel, Ramesh N.; Banerjee, Amit; Howell, J. M.; McNamee, Clyde G.; Brozozowski, David; Mirfakhrae, D.; Nanduri, Venkat; Thottathil, John K.; Szarka, Laszlo J.

doi:10.1016/s0957-4166(00)82256-9

Cited by 74 publications

(32 citation statements)

References 27 publications

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“…16,17 As a result, the use of microbial reduction to produce the desired isomer was investigated. A number of alcohol oxidoreductases from many organisms, including those from yeast, 18-23 horse liver, 24 Thermoanerobic brockii, 25,26 Lactobacillus kefir, 27 Pseudomonas sp., 28 Geotrichum candidum, 29,30 Hansenula polymorpha, 31,32 Mortierella rammaniana, 33 and Sulfolobus solfataricus 34 have proven useful for the enantioselective reduction of ketones to alcohols.…”

Section: Resultsmentioning

confidence: 99%

Diastereoselective microbial reduction of (S)-[3-chloro-2-oxo-1-(phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester

Patel¹,

Chu²,

Mueller³

2003

Tetrahedron: Asymmetry

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Section: Resultsmentioning

confidence: 99%

Diastereoselective microbial reduction of (S)-[3-chloro-2-oxo-1-(phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester

Patel¹,

Chu²,

Mueller³

2003

Tetrahedron: Asymmetry

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“…Chiral dihydroxy compound is an intermediate for our new anticholesterol drug. Recently, we have prepared C-13 side-chain of an anticancer drug, paclitaxel, by the stereoselective microbial reduction of 2-keto-3-(N-benzoylamino)-3-phenyl propionic acid ethyl ester to yield (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester (32). In this report, we have described the preparation of chiral chloroalcohol 2 by the stereoselective reduction process, as well as the preparation of two different chiral intermediates needed for the synthesis of β-3-receptor agonists.…”

Section: Discussionmentioning

confidence: 99%

Microbial synthesis of chiral intermediates for β‐3‐receptor agonists

Patel

Banerjee

Chu

et al. 1998

J Americ Oil Chem Soc

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Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of β-3-receptor agonists. These include: (i) the microbial reduction of 4-benzyloxy-3-methanesulfonylamino-2′-bromoacetophenone 1 to the corresponding (R)-alcohol 2 by Spingomonas paucimobilis SC 16113. In the biotransformation process, a reaction yield of >85% and an optical purity of 99.5% were obtained for the desired (R)-alcohol 2; (ii) the enzymatic resolution of racemic α-methyl phenylalanine amide, 3, and α-methyl-4-hydroxyphenylalanine amide, 5, by amidase from Mycobacterium neoaurum ATCC 25795 to prepare the corresponding (S)-amino acids 4 and 6. Reaction yields of 49.9 and 49 M% (theoretical maximum yield 50 M%) and optical purities of 99 and 94% were obtained for the desired (S)-amino acids 4 and 6, respectively; (iii) the asymmetric hydrolysis of methyl-(4-methoxyphenyl)-propanedioic acid, ethyl diester, 7, to the corresponding (S)-monoester 8 by pig liver esterase. A reaction yield of 96 M% and an optical purity of 96% were obtained for (S)-monoester 8 when reactions were carried out in a biphasic system containing 10% ethanol at 10°C.Much attention is currently focused on the interaction of small molecules with biological macromolecules. The search for selective enzyme inhibitors and receptor agonists or antagonists is one of the keys for target-oriented research in the pharmaceutical industry. Increasing understanding of the mechanism of drug interaction on a molecular level has led to growing awareness of the importance of chirality as the key to the efficacy of many drug products. It is now known that in many cases only one stereoisomer of a drug substance is required for efficacy; the other stereoisomer is either inactive or exhibits considerably reduced acitivity. Pharmaceutical companies are aware that, where the switch from racemate drug substance to enantiomerically pure compound is feasible, new drugs should be homochiral to avoid the possibility of side effects caused by an undesirable stereoisomer. There is the opportunity to double the use of an industrial process by obtaining a separate patent on the use of a single stereoisomer as a more efficient drug. The physical advantages of enantiomers over racemates may confer processing and formulation advantages, as well as lower doses.The advantages of microbial or enzyme-catalyzed reactions over chemical reactions are that they are stereoselective and can be carried out at ambient temperature and atmospheric pressure. These minimize problems of isomerization, racemization, epimerization, and rearrangement, which generally occur during chemical processes. Biocatalytic processes are usually carried out in aqueous solution. This avoids the use of solvent and other environmentally harmful chemicals used in the chemical processes. Furthermore, microbial cells or enzymes derived from biocatalysis can be immobilized and reused for many cycles. Recently, a number of review articles (1-9) have been published on the use of enzymes in organic synthesis.β-Adrenocepto...

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“…A further analogous microbial process by Rohner Ltd. was reported for the production of ethyl (1R,2S)-cis-2-hydroxycyclohexane carboxylic acid ethyl ester (70% yield, >97% de, >93% ee). Further microbial reductions with wild-type organisms comprise the synthesis of a chiral C-13 side-chain intermediate of paclitaxel by BMS researchers utilizing Hansenula fabianii cells, which were produced in a 15l-scale fermentation [77], as well as the synthesis of an N-acylated aminoalcohol with excellent conversion (>99% ee) and enantioselectivity (>98% ee) on a 280 l scale by researchers from Merck & Co. based on the use of Candida sorbophila whole cells [78,79]. A combination of ketone reduction with wild-type organisms and the use of XAD-7 resin to decrease the solubility of a substrate being toxic for the microorganism was reported by Eli Lilly researchers, thus obtaining the desired alcohol product in high yield (96%) and with >99.9% ee, even when operating at a high substrate loading of 80 g/l [80][81][82].…”

Section: Wild-type Whole Cellsmentioning

confidence: 99%

Asymmetric Synthesis with Recombinant Whole‐Cell Catalysts

2016

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c h a p t e r 2 3 INTRODUCTIONAsymmetric catalytic transformations play a central role in the field of organic chemistry and are of great interest for applications in the chemical and pharmaceutical industry. Among those, hydrolytic and reverse reactions to form carboxylate deriva tives as well as C─C bond-forming and redox reactions are of particular importance. For a long time this field was dominated by the use of chemocatalysts [1]. For example, numerous chiral heavy-metal complexes have been found to be highly efficient cat alysts, on a technical scale, in particular, for the asymmetric reduction of imines, ketones, and enamides. A representative success story is imine reduction for the man ufacture of metolachlor as one of the largest industrially applied asymmetric chemo catalytic processes to date, and the widely technically applied hydrogenation technology for the reduction of ketones and enamides, for which Noyori and Knowles were awarded the Nobel Prize [2]. An alternative for the production of chiral building blocks, with a continuously increasing number of examples, also on an industrial scale, is biocatalysis. Known for a long time, the use of biocatalytic alternatives has also been limited for a long time, which has been due to-among others-the following two reasons: (i) wild-type whole cells such as baker's yeast require a large amount of biomass (due to the forma tion of the desired enzymes in the cell only in low amounts) and often give unsatisfy ing enantioselectivities (due to the action of more than one enzyme), and (ii) the use of isolated enzymes requires additional costs for cell disruption and enzyme isolation as well as the addition of an external amount of cofactor. Due to impressive progress in the field of molecular biology, these limitations have often been overcome. High overexpression of the desired enzyme in recombinant host organism and high cell density fermentation technology provide efficient and economically attractive access to these microorganisms (so-called designer cells), which contain exclusively the desired biocatalyst (enzyme) in large amounts. Such designer cells can be used directly in organic synthetic reactions without the need to isolate the enzyme in additional downstream operation steps. The presence of the cofactor in the cells requires no addition of an external amount of cofactors or supply thereof in very low amount only. Due to these advantages, recombinant whole cells overexpressing cofactor dependent enzymes have become very attractive catalysts for asymmetric synthesis. This is underlined by an increasing number of recent organic biotransformations based on the use of such "designer cells."

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Microbial synthesis of (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester-a taxol side-chain synthon

Cited by 74 publications

References 27 publications

Diastereoselective microbial reduction of (S)-[3-chloro-2-oxo-1-(phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester

Diastereoselective microbial reduction of (S)-[3-chloro-2-oxo-1-(phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester

Microbial synthesis of chiral intermediates for β‐3‐receptor agonists

Asymmetric Synthesis with Recombinant Whole‐Cell Catalysts

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