40458-77-3Relevant articles and documents
Accessing tetrahydrofuran-based natural products by microbial Baeyer-Villiger biooxidation
Mihovilovic, Marko D.,Bianchi, Dario A.,Rudroff, Florian
, p. 3214 - 3216 (2006)
A heterobicyclic lactone obtained by stereoselective Baeyer-Villiger biooxidation with recombinant whole-cells expressing cyclopentanone monooxygenase from Comamonas sp. NCIMB 9872 was used for formal total syntheses of various natural products containing
Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions
Yu, Wensheng,Tong, Ling,Selyutin, Oleg,Chen, Lei,Hu, Bin,Zhong, Bin,Hao, Jinglai,Ji, Tao,Zan, Shuai,Yin, Jingjun,Ruck, Rebecca T.,Curry, Stephanie,McMonagle, Patricia,Agrawal, Sony,Rokosz, Laura,Carr, Donna,Ingravallo, Paul,Bystol, Karin,Lahser, Frederick,Liu, Rong,Chen, Shiying,Feng, Kung-I,Cartwright, Mark,Asante-Appiah, Ernest,Kozlowski, Joseph A.
, p. 3984 - 4003 (2018/05/14)
We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.
Synthesis of tetrahydrofuran-based natural products and their carba analogs via stereoselective enzyme mediated Baeyer–Villiger oxidation
Rudroff, Florian,Bianchi, Dario A.,Moran-Ramallal, Roberto,Iqbal, Naseem,Dreier, Dominik,Mihovilovic, Marko D.
, p. 7212 - 7221 (2016/10/29)
In this work we present efficient formal syntheses of several biologically interesting natural products (showdomycin, goniofufurone, trans-kumausyne) and their novel carba analogs by applying different Baeyer–Villiger monooxygenases. This strategy provides access to tetrahydrofuran-based natural products, C-nucleosides and both antipodes of the corresponding carba analogs in high optical purities (up to >95% ee) starting from simple achiral and commercially available building blocks (tetrabromoacetone, furan and cyclopentadiene). The striking key features of this chemo-enzymatic approach are the introduction of four stereogenic centers in as few as three reaction steps within a desymmetrization approach and the short-cut of several reaction sequences by the implementation of a biocatalytic step.
Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna
Li, Jing,Van Belkum, Marco J.,Vederas, John C.
experimental part, p. 4356 - 4363 (2012/08/28)
(-)-Hyoscyamine, the enantiomerically pure form of atropine, and its derivative scopolamine are tropane alkaloids that are extensively used in medicine. Hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a monomeric α-ketoglutarate dependent dioxygenase, converts (-)-hyoscyamine to its 6,7-epoxy derivative, scopolamine, in two sequential steps. In this study, H6H of Atropa belladonna (AbH6H) was cloned, heterologously expressed in Escherichia coli, purified and characterized. The catalytic efficiency of AbH6H, especially for the second oxidation, was found to be low, and this may be one of the reasons why Atropa belladonna produces less scopolamine than other species in the same family. 6,7-Dehydrohyoscyamine, a potential precursor for the last step of epoxidation, was shown not to be an obligatory intermediate in the biosynthesis of scopolamine using purified AbH6H with an in vitro 18O labeling experiment. Moreover, the nitrogen atom in the tropane ring of (-)-hyoscyamine was found to play an important role in substrate recognition.
HEPATITIS C VIRUS INHIBITORS
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Page/Page column 66-67, (2012/03/09)
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment o
Facile synthesis and ring-opening cross metathesis of carbo- and heterocyclic bicyclo[3.2.1]oct-6-en-3-ones using gaseous olefinic reaction partners
Mihovilovic, Marko D.,Groetzl, Birgit,Kandioller, Wolfgang,Snajdrova, Radka,Muskotal, Adel,Bianchi, Dario A.,Stanetty, Peter
, p. 463 - 470 (2007/10/03)
The title compounds were prepared by a facile [4+3]-cycloaddition strategy involving sonochemistry. The oxyallyl species required for the reaction with the corresponding diene was generated from a suitable perbromo ketone with activated zinc under sonific
Synthesis of the C38-C44 segment of altohyrtin A - with an addendum on the preparation of 8-oxabicyclo[3,2.1]oct-6-en-3-one
Kim,Hoffmann
, p. 2195 - 2201 (2007/10/03)
The densely funtionalized C38-C44 segment F of altohyrtin A with its five contiguous stereogenic centers was prepared in 10 steps and in 28% overall yield (two steps per stereogenic center), from 8- oxabicyclo[3.2.1]oct-6-en-3-one as a template. The preparation of the title compound 1, m.p. 38 °C, is described on a 0.5 m scale in a three-step-two- stage reaction from acetone anti furan. The oxacycle was stored without change at room temperature.
Synthesis of 8-oxa analogues of norcocaine endowed with interesting cocaine-like activity
Kozikowski, Alan P.,Simoni, Daniele,Roberti, Marinella,Rondanin, Riccardo,Wang, Shaomeng,Du, Pingfeng,Johnson, Kenneth M.
, p. 1831 - 1836 (2007/10/03)
In order to further explore the importance of cocaine's bridge nitrogen atom in binding to the dopamine transporter (DAT), we have synthesized the previously known racemic 8-oxa-norcocaines 3-6 in which the nitrogen atom has been replaced by oxygen. Additionally, to avoid incorrect interpretations of biological data that may stem from the use of racemic materials, several of these analogues were synthesized and tested in non-racemic form. (-)-8-Oxa- norcocaine (3) was found to bind to the cocaine recognition site and to inhibit the dopamine transporter with potencies only about 8-fold and 4- fold, respectively, less than those of norcocaine (2). (-)-8-Oxa- pseudonorcocaine (4) as well as (+)-8-oxa-norcocaine (3) were found to be comparable in activity to (-)-oxa-norcocaine. These pharmacological findings support our earlier suggestion that cocaine is likely to bind in its neutral form to the DAT.
Asymmetric synthesis of polyacetate derived building clocks with α- oxyanion functionality. Lewis acid catalyzed opening of 2,9- dioxabicyclo[3.3.1]nonan-3-ones
Dunkel, Ralf,Hoffmann
, p. 8385 - 8396 (2007/10/03)
All four stereoisomeric cyclic 3,5,7-trihydroxyheptanoic acid equivalents of the polyacetate aldol type (Scheme 1) are obtainable from 8- oxabicyclo[3.2.1]oct-6-en-3-one which functions as a meso-configurated 4-way optical switch. Lewis acid assisted nucl
HIGHLY STEREOSELECTIVE, TOTAL SYNTHESIS OF β-C-HEXOPYRANOSYL DERIVATIVES
Fattori, Daniela,Vogel, Pierre
, p. 1017 - 1018 (2007/10/02)
One Diels-Alder adduct of furan to 1-cyanovinyl acetate is converted to 8-oxabicyclooct-6-en-2-one which is transformed into β-C-hexopyranosides including 2-deoxy and 2,3-unsaturated derivatives.