- Biocatalytic Strategy for Highly Diastereo- and Enantioselective Synthesis of 2,3-Dihydrobenzofuran-Based Tricyclic Scaffolds
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2,3-Dihydrobenzofurans are key pharmacophores in many natural and synthetic bioactive molecules. A biocatalytic strategy is reported here for the highly diastereo- and enantioselective construction of stereochemically rich 2,3-dihydrobenzofurans in high enantiopurity (>99.9% de and ee), high yields, and on a preparative scale via benzofuran cyclopropanation with engineered myoglobins. Computational and structure-reactivity studies provide insights into the mechanism of this reaction, enabling the elaboration of a stereochemical model that can rationalize the high stereoselectivity of the biocatalyst. This information was leveraged to implement a highly stereoselective route to a drug molecule and a tricyclic scaffold featuring five stereogenic centers via a single-enzyme transformation. This work expands the biocatalytic toolbox for asymmetric C–C bond transformations and should prove useful for further development of metalloprotein catalysts for abiotic carbene transfer reactions.
- Vargas, David A.,Khade, Rahul L.,Zhang, Yong,Fasan, Rudi
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supporting information
p. 10148 - 10152
(2019/07/04)
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- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS
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Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
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- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS
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Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
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- PHARMACEUTICAL COMPOSITION FOR TREATING DIABETES
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Provided is a compound represented by the following general formula (I), or a pharmaceutically acceptable salt thereof. This novel compound has a glycogen-synthase activation ability, but activates a receptor PPAR to a low degree and is highly safe. In th
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Paragraph 0076
(2014/09/29)
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- Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists
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The present invention provides serotonergic aminoalkylbenzofurans of Formula (I): where R, R1, R2, R3, R4, R4′, R5, R5′, and R12 are as described in the specification.
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Page/Page column 18
(2010/11/08)
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- SEROTONERGIC BENZOFURANS
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The present invention provides serotonergic benzofurans of Formula (I): where A, R, R, R, R, and R are as described in the specification.
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- BENZOFURYLPIPERAZINES AND BENZOFURYLHOMOPIPERAZINES: SEROTONIN AGONISTS
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The present invention provides serotonergic benzofurylpiperazines of Formula I: where: A is a piperazine of formula: and R, R1, R2, R3, R4, R5, R5', R6, R6', R7, R7', R8, and R8' are as described in the specification.
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- Azepine derivatives having effects on serotonin related systems
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The present invention provides compounds of formula I and a method of inhibiting the reuptake of serotonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of suc
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- Piperidine derivatives having effects on serotonin related systems
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The present invention provides the compounds of the following formula: Wherein the variables are as defined in the specification and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of such treatment an effective amount of the compound of above formula.
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- Pyrrolidine and pyrroline derivatives having effects on serotonin related systems
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The present invention provides the compounds of the following formula (I): and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1Areceptor and antagonizing the 5-HT2Areceptor which comprises administering to a subject in need of such treatment an effective amount of formula (I).
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Page column 43
(2010/02/05)
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