140630-45-1Relevant articles and documents
Exploring the Biocatalytic Scope of a Novel Enantioselective Halohydrin Dehalogenase from an Alphaproteobacterium
Xue, Feng,Ya, Xiangju,Xiu, Yuansong,Tong, Qi,Wang, Yuqi,Zhu, Xinhai,Huang, He
, p. 629 - 637 (2019/01/25)
A gene encoding halohydrin dehalogenase from an alphaproteobacterium (AbHHDH) was identified, cloned and over-expressed in Escherichia coli. AbHHDH was able to catalyze the stereoselective dehalogenation of prochiral and racemic halohydrins. It showed the highest enantioselectivity in the dehalogenation of 20?mM (R,S)-2-bromo-1-phenylethanol, which yielded (S)-2-bromo-1-phenylethanol with 99% ee and 34.5% yield. Moreover, AbHHDH catalyzed the azidolysis of epoxides with low to moderate (S)-enantioselectivity. The highest enantioselectivity (E = 18.6) was observed when (R,S)-benzyl glycidyl ether was used as the substrate. A sequential kinetic resolution catalyzed by HHDH was employed for the synthesis of chiral 1-chloro-3-phenoxy-2-propanol. We prepared enantiopure (S)-isomer with a high enantiopurity of ee > 99% and a yield of 30.7% (E-value: 21.3) by kinetic resolution of 20?mM substrate. The (S)-isomer with 99% ee readily obtained from 40 to 150?mM (R,S)-1-chloro-3-phenoxy-2-propanol. Taken together, the results of this study demonstrate the applicability of this HHDH for the production of optically active compounds. [Figure not available: see fulltext.].
Highly enantioselective CALB-catalyzed kinetic resolution of building blocks for β-blocker atenolol
Lund, Ingvild T.,B?ckmann, P?l L.,Jacobsen, Elisabeth E.
, p. 7288 - 7292 (2016/10/26)
Both enantiomers of 4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide has been synthesized in 98.5–99% enantiomeric excess by use of lipase B from Candida antarctica as catalyst. The R-alcohol is a building block for the cardioselective β-blocker (S)-atenolol ((S)-2-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide. Performing kinetic resolutions of 3-chloro-1-phenoxy-2-propanol and 3-bromo-1-phenoxy-2-propanol with vinyl butanoate as acyl donor and the same CALB enzyme, but a different preparation, showed higher E-values than previously reported.
Tuning of the electronic properties of a cyclopentadienylruthenium catalyst to match racemization of electron-rich and electron-deficient alcohols
Verho, Oscar,Johnston, Eric V.,Karlsson, Erik,Baeckvall, Jan-E.
experimental part, p. 11216 - 11222 (2011/11/05)
The synthesis of a new series of cyclopentadienylruthenium catalysts with varying electronic properties and their application in racemization of secondary alcohols are described. These racemizations involve two key steps: 1) β-hydride elimination (dehydrogenation) and 2) re-addition of the hydride to the intermediate ketone. The results obtained confirm our previous theory that the electronic properties of the substrate determine which of these two steps is rate determining. For an electron-deficient alcohol the rate-determining step is the β-hydride elimination (dehydrogenation), whereas for an electron-rich alcohol the re-addition of the hydride becomes the rate-determining step. By matching the electronic properties of the catalyst with the electronic properties of the alcohol, we have now shown that a dramatic increase in racemization rate can be obtained. For example, electron-deficient alcohol 15 racemized 30 times faster with electron-deficient catalyst 6 than with the unmodified standard catalyst 4. The application of these protocols will extend the scope of cyclopentadienylruthenium catalysts in racemization and dynamic kinetic resolution. Copyright
