- SCALABLE SYNTHESIS OF OPTICALLY ACTIVE 1-CYCLOPROPYLALKYL-1-AMINES
-
The present invention provides a new, scalable synthetic method for the preparation of non-racemic 1-cyclopropyl alkyl-1-amines, e.g. (S)- 1-cyclopropyl ethyl-1-amine. The method makes use of inexpensive starting materials (such as cyclopropyl methyl keto
- -
-
Page/Page column 7-8
(2020/05/26)
-
- Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
-
ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.
- Han, Sang-Woo,Shin, Jong-Shik
-
p. 3287 - 3295
(2019/06/21)
-
- Asymmetric Amination of Secondary Alcohols by using a Redox-Neutral Two-Enzyme Cascade
-
Multienzyme cascade approaches for the synthesis of optically pure molecules from simple achiral compounds are desired. Herein, a cofactor self-sufficient cascade protocol for the asymmetric amination of racemic secondary alcohols to the corresponding chiral amines was successfully constructed by employing an alcohol dehydrogenase and a newly developed amine dehydrogenase. The compatibility and the identical cofactor dependence of the two enzymes led to an ingenious in situ cofactor recycling system in the one-pot synthesis. The artificial redox-neutral cascade process allowed the transformation of racemic secondary alcohols into enantiopure amines with considerable conversions (up to 94 %) and >99 % enantiomeric excess at the expense of only ammonia; this method thus represents a concise and efficient route for the asymmetric synthesis of chiral amines. If you know what amine: A redox-neutral two-enzyme cascade encompassing an alcohol dehydrogenase (ADH) and an amine dehydrogenase (AmDH) is constructed for the synthesis of chiral amines from the corresponding racemic alcohols in one pot to afford considerable conversions (up to 94 %) and high enantiomeric excess values (>99 %) at the expense of only ammonia.
- Chen, Fei-Fei,Liu, You-Yan,Zheng, Gao-Wei,Xu, Jian-He
-
p. 3838 - 3841
(2016/01/26)
-
- Anthranilamide insecticides
-
Disclosed are intermediate compounds for use in the synthesis of compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein J is a phenyl optionally substituted with one to four substituents independently selected from R5; or J is a heterocyclic ring selected from the group consisting of J-1 to J-8; R4 is C4-C12 alkylcycloalkyl, C5-C12 alkenylcycloalkyl, C5-C12 alkynylcycloalkyl, C4-C12 cycloalkylalkyl, C5-C12 cycloalkylalkenyl, C5-C12 cycloalkylalkynyl, C4-C12 cycloalkenylalkyl or C4-C12 alkylcycloalkenyl; each optionally substituted with one to six substituents selected from CH3 and halogen; or R4 is C3-C5 oxiranylalkyl, C3-C5 thiiranylalkyl, C4-C6 oxetanylalkyl, C4-C6 thietanylalkyl, 3-oxetanyl or 3-thietanyl, each optionally substituted with one to five substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, halogen, CN, C2-C4 alkoxycarbonyl and C2-C4 haloalkoxycarbonyl; or R4 is C3-C5 aziridinylalkyl, C4-C6 azetidinylalkyl or 3-azetidinyl, each with R10 attached to the nitrogen atom, and optionally substituted on carbon atoms with one to five substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, halogen, CN, C2-C4 alkoxycarbonyl and C2-C4 haloalkoxycarbonyl; and R1a R1b R2 R3 and R5 are as defined in the disclosure.
- -
-
-
- ω-Transaminase-catalyzed kinetic resolution of chiral amines using l-threonine as an amino acceptor precursor
-
Kinetic resolution of chiral amines using l-threonine as a cosubstrate was demonstrated by a biocatalytic strategy in which (S)-selective ω-transaminase (ω-TA) was coupled with threonine deaminase (TD), eliminating the need to use an expensive keto acid as an amino acceptor. The coupled enzyme reaction enabled simultaneous production of enantiopure (R)-amine and l-homoalanine which are pharmaceutically important building blocks. To extend the versatility of this strategy to production of both enantiomers of chiral amines, (R)-selective ω-TA coupled with TD was employed to produce (S)-amine.
- Malik, M. Shaheer,Park, Eul-Soo,Shin, Jong-Shik
-
supporting information; experimental part
p. 2137 - 2140
(2012/09/25)
-
- PROCESS FOR PRODUCTION OF ANTHRANILAMIDE COMPOUND
-
To provide a process for producing a specific anthranilamide compound or its salt. To provide a process for producing an anthranilamide compound represented by the formula (I) or its salt: wherein each of R1a and R3 which are independent of each other, is halogen or haloalkyl; R2 is cyclopropyl alkyl or cyclobutyl alkyl; and Hal is a chlorine atom or a bromine atom, which comprises a step of selectively halogenating a compound represented by the formula (II): wherein R1a, R2 and R3 are as defined above.
- -
-
Page/Page column 41
(2009/09/07)
-
- Influence of bulky substituents on histamine H3 receptor agonist/antagonist properties
-
Novel derivatives of 3-(1H-imidazol-4-yl)propanol were designed on the basis of lead compounds belonging to the carbamate or ether series possessing (partial) agonist properties on screening assays of the histamine H3 receptor. One pair of enantiomers in the series of α-methyl-branched chiral carbamates was stereoselectively prepared in high optical yields. Enantiomeric purity was checked by Mosher amide derivatives of precursors and capillary electrophoresis of the final compounds with trimethyl-β-cyclodextrin as chiral selector, and was determined to be ≥95%. The novel compounds were investigated in various histamine H3 receptor assays in vitro and in vivo. Some compounds displayed partial agonist activity on synaptosomes of rat brain cortex, whereas others exhibited antagonist properties only. Selected compounds were investigated in [125I]iodoproxyfan binding studies on the human histamine H3 receptor and showed high affinity in the nanomolar concentration range. Under in vivo conditions after oral administration to mice, some of the compounds exhibited partial or full agonist activity in the brain at low dosages. The (S)-enantiomer of one pair of chiral carbamates (9) proved to be the eutomer; thus, the (S)-enantiomer was selected for further pharmacological studies. In a peripheral in vivo test model in rats, measuring the level of inhibition of capsaicin-induced plasma extravasation, (S)-9 again proved its high oral agonist potency with full intrinsic activity (ED50 values of 0.07-0.1 mg/kg depending on tissue).
- Sasse, Astrid,Ligneau, Xavier,Rouleau, Agnès,Elz, Sigurd,Ganellin, C. Robin,Arrang, Jean-Michel,Schwartz, Jean-Charles,Schunack, Walter,Stark, Holger
-
p. 4000 - 4010
(2007/10/03)
-
