102045-96-5Relevant articles and documents
Mapping the substrate selectivity of new hydrolases using colorimetric screening: Lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
Liu, Andrew Man Fai,Somers, Neil A.,Kazlauskas, Romas J.,Brush, Terry S.,Zocher, Frank,Enzelberger, Markus M.,Bornscheuer, Uwe T.,Horsman, Geoff P.,Mezzetti, Alessandra,Schmidt-Dannert, Claudia,Schmid, Rolf D.
, p. 545 - 556 (2001)
Recent advances in biochemistry and molecular biology have simplified the discovery and preparation of new hydrolases. Although these hydrolases might solve problems in organic synthesis, measuring their selectivity, especially enantioselectivity, remains tedious and time consuming. Recently, we developed a colorimetric screening method to measure the enantioselectivity of hydrolases. Here we apply this rapid screening method to map the substrate selectivity of four new hydrolases: lipases from the thermophilic Bacillus thermocatenulatus (DSM 730, BTL2) and a filamentous fungus Ophiostoma piliferum (NRRL 18917, OPL) and esterases from two bacteria, Pseudomonas fluorescens (SIK-W1, esterase I, PFE) and Streptomyces diastatochromogenes (Tue 20, SDE). We screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective reactions were identified for the solketal esters: BTL2, butyrate, E = 7.9 (R); octanoate, E = 4.9 (R) and 3-bromo-2-methyl propionate methyl esters, PFE, E = 12 (S); SDE, E = 5.6 (S). OPL showed low enantioselectivity toward all substrates tested. The current colorimetric screen could not measure the selectivity for several slow-reacting substrates. Traditional screening identified high enantioselectivity of BTL2 and PFE toward one of these slow substrates, 1-phenylethyl acetate (E>50).
Scope and Mechanism of Deprotection of Carboxylic Esters by Bis(tributyltin) Oxide
Salomon, Claudio J.,Mata, Ernesto G.,Mascaretti, Oreste A.
, p. 7259 - 7266 (1994)
Methyl and ethyl esters of aliphatic and aromatic carboxylic acids as well as benzyl carboxylates, thiol esters and double esters such as (pivaloyloxy)methyl carboxylates have been successfully cleaved with bis(tributyltin) oxide to give the free carboxylic acids in good yields.The reaction is carried out in aprotic solvents under essentially neutral conditions and thus this method can serve as an ideal procedure for the cleavages of esters with other functional groups and/or protecting groups acid and/or base sensitive.We demonstrated that the reaction displays a high level of chemoselectivity between methyl and ethyl esters versus tert-butyl esters and γ-lactones.Bis(tributyltin) oxide is also a highly efficient reagent for the cleavage of acetates of primary and secondary alcohols and phenols.The limitations we found in the use of this reagent include the lack of cleavage of esters sterically hindered around the carboxyl carbon and the carbinol group (i.e., esters of tertiary alcohols) and in carboxylic esters that contain a fluoroalkyl substituent.A resonable mechanistic explanation is discussed to account for the reaction pathway of the acyloxygen cleavage of (-)-(1R)-menthyl acetate.
THERAPEUTIC METHODS
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Page/Page column 135; 141-142, (2020/05/28)
The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
METHODS FOR TREATING HEPATITIS B INFECTIONS
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Page/Page column 209-210, (2019/04/09)
Certain embodiments of the invention provide a method for identifying a patient that has a higher likelihood of responding to an HBV antigen inhibitor, such a method comprising detecting a hepatitis B virus (HBV) infected patient's genotype at one or more of the IL28B/A associated SNPs described herein, wherein the relevant genotype(s) described herein are indicative of a patient that has a higher likelihood of responding to an HBV antigen inhibitor as compared to an HBV infected patient having different genotypes at these locations.
TARGETED COMPOSITIONS
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Page/Page column 129; 130, (2018/11/10)
The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS
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Page/Page column 102; 103, (2017/11/10)
The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
STEROL DERIVATIVES AND USE THEREOF FOR TREATING DISEASES INVOLVING TRANSFORMED ASTROCYTE CELLS OR FOR TREATING MALIGNANT HAEMOPATHIES
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Page/Page column 25, (2013/12/03)
The invention relates to novel sterol derivatives, the preparation method thereof, pharmaceutical compositions containing them and use thereof for treating diseases involving transformed astrocyte cells or for treating malignant haemopathies. The inventio
NOVEL COMPOUND 395
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Page/Page column 10, (2010/02/17)
A compound of formula (1) and pharmaceutically acceptable salts thereof for use in the treatment of chemokine mediated diseases and conditions.
Studies on the synthesis of (-)-gymnodimine. Subunit synthesis and coupling
White, James D.,Quaranta, Laura,Wang, Guoqiang
, p. 1717 - 1728 (2007/10/03)
Two principal subunits of the marine algal toxin (-)-gymnodimine were synthesized. A trisubstituted tetrahydrofuran representing C10-C18 of the toxin was prepared via a highly stereoselective iodine-mediated cyclization of an acyclic alkene bearing a bis-
8-Azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 23, (2008/06/13)
The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.