Xi:Irritant;10488-69-4Relevant academic research and scientific papers
Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ace) inhibitors in high space-time yield by a new reductase without external cofactors
Shen, Nai-Dong,Ni, Yan,Ma, Hong-Min,Wang, Li-Juan,Li, Chun-Xiu,Zheng, Gao-Wei,Zhang, Jie,Xu, Jian-He
, p. 1982 - 1985 (2012)
A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L-1·d -1) was 27 times higher than the highest record.
A practical asymmetric synthesis of a 1,7-enyne A-ring synthon en route toward the total synthesis of vitamin D3 analogues
Trost, Barry M.,Hanson, Paul R.
, p. 8119 - 8122 (1994)
A concise synthesis of a key A-ring synthon of 1α,25-dihydroxyvitamin D3, 1, has been achieved in 8 steps starting from readily available, inexpensive ethyl-4-chloroacetoacetate. This synthon serves as one of two main coupling partners in our previously developed Pd-catalyzed alkylative enyne cyclization leading toward the total synthesis of la,25-dihydroxyvitamin D3 and potentially useful analogues.
Stereoselective reduction of α- and β-keto esters with aerobic thermophiles, Bacillus strains
Ishihara, Kohji,Iwai, Keisuke,Yamaguchi, Hitomi,Nakajima, Nobuyoshi,Nakamura, Kaoru,Ohshima, Toshihisa
, p. 1896 - 1898 (1996)
The first example of stereoselective reduction with aerobic thermophiles is reported. Various α- and β-keto esters were reduced stereoselectively to the corresponding alcohols by the aerobic thermophiles, Bacillus strains. In particular, the reduction of ethyl 3-methyl-2-oxobutanoate with B. stearothermophilus DSM 297 gave the corresponding (R)-alcohol with high yield in excellent enantioselectively (> 99% e.e.). The conversions of keto esters to the corresponding hydroxy esters with Bacillus strains were increased by introduction of glycerol in the reaction mixture as an additive.
A NEW METHOD FOR STEREOCHEMICAL CONTROL OF MICROBIAL REDUCTION. REDUCTION OF β-KETO ESTERS WITH BAKERS' YEAST IMMOBILIZED BY MAGNESIUM ALGINATE
Nakamura, Kaoru,Kawai, Yasushi,Oka, Shinzaburo,Ohno, Atsuyoshi
, p. 2245 - 2246 (1989)
Yeast reduction of methyl 3-oxopentanoate gives the L-hydroxy ester when bakers' yeast is immobilized by magnesium alginate and the reaction is run under a high concentration of magnesium ion.The D-hydroxy ester is obtained under normal reaction conditions.
Preparation of structurally diverse chiral alcohols by engineering ketoreductase CgKR1
Zheng, Gaowei,Liu, Yuan-Yang,Chen, Qi,Huang, Lei,Yu, Hui-Lei,Lou, Wen-Yong,Li, Chun-Xiu,Bai, Yun-Peng,Li, Ai-Tao,Xu, Jian-He
, p. 7174 - 7181 (2017)
Ketoreductases are tools for the synthesis of chiral alcohols in industry. However, the low activity of natural enzymes often restricts their use in industrial applications. On the basis of computational analysis and previous reports, two residues (F92 and F94) probably affecting the activity of ketoreductase CgKR1 were identified. By tuning these two residues, the CgKR1-F92C/F94W variant was obtained that exhibited higher activity toward all 28 structurally diverse substrates examined than the wild-type enzyme. Among them, 13 substrates have a specific activity over 50 U mg-1 (54-775 U mg-1). Using CgKR1-F92C/F94W as a catalyst, five substrates at high loading (>100 g-1 L-1) were reduced completely in gramscale preparative reactions. This approach provides accesses to pharmaceutically relevant chiral alcohols with high enantioselectivity (up to 99.0% ee) and high space-time yield (up to 583 g-1 L-1 day-1). Molecular dynamics simulations highlighted the crucial role of residues 92 and 94 in activity improvement. Our findings provide useful guidance for engineering other ketoreductases, especially those possessing a similar active pocket to that in CgKR1.
Practical Enzymatic Route to Optically Active 3-Hydroxyamides. Synthesis of 1,3-Aminoalcohols
Garcia, Maria Jesus,Rebolledo, Francisca,Gotor, Vicente
, p. 2199 - 2210 (1993)
Candida antarctica lipase (CAL) is a very efficient catalyst for the enantioselective aminolysis of different racemic 3-hydroxyesters with aliphatic amines.The degree of enantioselectivity exhibited by the lipase depends on the substrate and nucleophile, but in the most cases, the E values obtained are very satisfactory.CAL also catalyzes the aminolysis of ethyl (+/-)-3,4-epoxybutyrate and the epoxyamide was achieved with high e. e.The chemical reduction of the 3-hydroxyamides obtained by enzymatic aminolysis yields the corresponding 1,3-aminoalcohols.
Efficient synthesis of an ε-hydroxy ester in a space-time yield of 1580 g L-1 d-1 by a newly identified reductase RhCR
Chen, Rui-Jie,Zheng, Gao-Wei,Ni, Yan,Zeng, Bu-Bing,Xu, Jian-He
, p. 1501 - 1504 (2014)
A new NADH-dependent carbonyl reductase RhCR capable of efficiently reducing the ε-ketoester ethyl 8-chloro-6-oxooctanoate (ECOO) to give ethyl (S)-8-chloro-6-hydroxyoctanoate [(S)-ECHO], an important chiral precursor for the synthesis of (R)-α-lipoic acid, was identified from Rhodococcus sp. ECU1014. Using recombinant Escherichia coli cells expressing RhCR and glucose dehydrogenase used for the regeneration of cofactor, 440 g L-1 (2 M) of ECOO were stoichiometrically converted to (S)-ECHO in a space-time yield of 1580 g L-1 d-1 without the external addition of any expensive cofactor.
Lipase-catalyzed asymmetric synthesis of 6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones and their conversion to chiral 5,6-epoxyhexanoates
Sakaki,Sakoda,Sugita,Sato,Kaneko
, p. 343 - 346 (1991)
Highly enantioselective syntheses of (R)- and (S)-6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones by means of lipase-catalyzed kinetic resolutions are described. Chiral dioxinones thus obtained have been converted to optically active 5,6-epoxyhexanoates, which are important precursors for a series of biologically active compounds.
Baker's yeast: Improving the D-stereoselectivity in reduction of 3-oxo esters
Dahl, Allan C.,Fjeldberg, Morten,Madsen, Jorgen gaard
, p. 551 - 559 (1999)
The stereoselectivity of baker's yeast in the reduction of ethyl 3- oxopentanoate was shifted towards the corresponding (R)-hydroxy ester by sugar, heat treatment and allyl alcohol. The highest enantiomeric excesses obtained with baker's yeast with a good reduction capacity, 92-97%, were achieved by combining allyl alcohol and sugar; heat treatment did not increase the stereoselectivity further. With the use of this technique, ethyl (R)-3-hydroxyhexanoate, >99% ee, and ethyl (S)-4-chloro-3-hydroxybutanoate, 82-90% ee, were produced from the corresponding esters, and for the first time an excess of the (R)-enantiomer of ethyl 3-hydroxybutanoate was obtained with ordinary baker's yeast.
Stereochemical Control in Microbial Reduction. 8. Stereochemical Control in Microbial Reduction of β-Keto Esters
Nakamura, Kaoru,Kawai, Yasushi,Oka, Shinzaburo,Ohno, Atsuyoshi
, p. 875 - 879 (1989)
Stereochemistry of the reduction of β-keto esters with bakers' yeast is controlled by the addition of a certain α,β-unsaturated carbonyl compound (or its reduced form).Glucose also exerts the same effect.The additives tend to shift the stereochemistry of the reduction toward the production of D-hydroxy ester.Namely, methyl 3-oxopentanoate and ethyl 3-oxo-6-heptenoate were reduced to the corresponding D-hydroxy esters with excellent stereoselectivities and chemical yields.The enones are supposed to inhibit the enzymes that produce the L-hydroxy ester, whereas glucose plays a role to activate the enzymes that produce the D-hydroxy ester.
