4361-06-2Relevant articles and documents
Iodonium Ylides as Carbene Precursors in Rh(III)-Catalyzed C-H Activation
Jiang, Yuqin,Li, Pengfei,Li, Xingwei,Liu, Bingxian,Zhao, Jie
supporting information, p. 7475 - 7479 (2020/10/12)
The rhodium(III)-catalyzed coupling of C-H substrates with iodonium ylides has been realized for the efficient synthesis of diverse cyclic skeletons, where the iodonium ylides have been identified as efficient and outstanding carbene precursors. The reaction systems are applicable to both sp2 and sp3 C-H substrates under mild and redox-neutral conditions. The catalyst loading can be as low as 0.5 mol % in a gram-scale reaction. Representative products exhibit cytotoxicity toward human cancer cells at nanomolar levels.
Exploring the Promiscuous Enzymatic Activation of Unnatural Polyketide Extender Units in Vitro and in Vivo for Monensin Biosynthesis
Grote, Marius,Schulz, Frank
, p. 1183 - 1189 (2019/03/11)
The incorporation of new-to-nature extender units into polyketide synthesis is an important source for diversity yet is restricted by limited availability of suitably activated building blocks in vivo. We here describe a straightforward workflow for the biogenic activation of commercially available new-to-nature extender units. Firstly, the substrate scope of a highly flexible malonyl co-enzyme A synthetase from Streptomyces cinnamonensis was characterized. The results were matched by in vivo experiments in which the said extender units were accepted by both the polyketide synthase and the accessory enzymes of the monensin biosynthetic pathway. The experiments gave rise to a series of predictable monensin derivatives by the exploitation of the innate substrate promiscuity of an acyltransferase and downstream enzyme functions.
Synthesis of Enantiomerically Enriched 2-Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3-Diols Mediated by Acetobacter aceti
Brenna, Elisabetta,Cannavale, Flavia,Crotti, Michele,De Vitis, Valerio,Gatti, Francesco G.,Migliazza, Gaia,Molinari, Francesco,Parmeggiani, Fabio,Romano, Diego,Santangelo, Sara
, p. 3796 - 3803 (2016/12/24)
The stereoselective desymmetrisation of achiral 2-alkyl-1,3-diols is performed by oxidation of one of the two enantiotopic primary alcohol moieties by means of Acetobacter aceti MIM 2000/28 to afford the corresponding chiral 2-hydroxymethyl alkanoic acids (up to 94 % ee). The procedure, carried out in aqueous medium under mild conditions of pH, temperature and pressure, contributes to enlarge the portfolio of enzymatic oxidations available to organic chemists for the development of sustainable manufacturing processes.
QUINOLINYL MODULATORS OF RORyt
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Paragraph 0587; 0588, (2015/04/28)
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
A ring-closing metathesis approach for the synthesis of (±)-pregabalin
Bobade, Vivek D.,Mhaske, Pravin C.,Vadgaonkar, Kamlesh S.,Shelke, Shivaji H.
scheme or table, p. 847 - 851 (2012/08/27)
Efficient utilization of a Mannich-type reaction and the ring-closing metathesis (RCM) approach that leads to a convenient synthesis of 3-(aminomethyl)-5-methylhexanoic acid (pregabalin) is described. Springer-Verlag 2011.
Stereocontrolled alkylative construction of quaternary carbon centers
Kummer, David A.,Chain, William J.,Morales, Marvin R.,Quiroga, Olga,Myers, Andrew G.
supporting information; experimental part, p. 13231 - 13233 (2009/02/06)
Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α,α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. Copyright
INHIBITORS OF METALLOPROTEASES, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME AND METHODS OF THEIR USE
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, (2008/06/13)
Disclosed are novel inhibitors of metalloproteases, in particular matrix metalloproteases. The disclosed inhibitors are mercaptoketone and mercaptoalcohol compounds which are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, for example, arthropathy, dermatological conditions, bone resorption, inflammatory diseases, and tumor invasion and in the promotion of wound healing.
INHIBITORS OF COLLAGENASE-1 AND STORMELYSIN-1 METALLOPROTEASES, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME AND METHODS OF THEIR USE
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, (2008/06/13)
Disclosed are novel inhibitors of collagenase-1 and stromelysin-I metalloproteases. The disclosed inhibitors are mercaptoketone and mercaptoalcohol compounds which are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, for example, arthropathy, dermatological conditions, bone resorption, inflammatory diseases, and tumor invasion and in the promotion of wound healing.
SULFOXIMINE AND SULDODIIMINE MATRIX METALLOPROTEINASE INHIBITORS
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, (2008/06/13)
Novel sulfoximine and sulfodiimine matrix metalloproteinase inhibitors of the formula, STR1 wherein: R 1 is selected from the group consisting of lower-alkyl, hydroxy lower-alkyl, amino lower-alkyl, carbamoyl lower-alkyl, lower-alkyl carbonyl, lower-alkyoxyalkyl, aralkyl and heteroaralkyl;X is NH or O;R 2 is selected from the group consisting of hydrogen, lower-alkyl and aralkyl;R 3 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, aralkyl and heteroaralkyl; andR 4 is selected from the group consisting of lower alkyl, aralkyl and--CH(R 5)--C(O)NH 2, wherein R 5 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, hydroxymethyl, 1-hydroxyethyl, mercapto lower-alkyl, and methylthio lower-alkyl;useful for modulating physiological functions or treating diseases and disease conditions associated with matrix metalloproteinase modulation.
Phosphoramidate peptide inhibitors of human skin fibroblast collagenase
Kortylewicz,Galardy
, p. 263 - 273 (2007/10/02)
An extensive series of N-(monoethylphosphoryl)peptides was synthesized and their inhibition of purified human skin fibroblast collagenase examined. At the cleavage site S1 all reported compounds have the (EtO)(OK)P(O) group and the peptide side chain extended toward the C-terminal end (up to P5') of the substrate sequence. These phosphoramidates with a tetrahedrally hybridized phosphorus atom are thought to be transition state analogue inhibitors. They exhibited fair inhibitory potency against this vertebrate collagenase having K(i) values in the micromolar range. The most potent of these, (EtO)(OK)P(O)-Ile-TrpNHCH3 (68), inhibits with a K(i) value of 1.5 μM and is nearly 100 times stronger than (EtO)(OK)P(O)-Ile-Ala-GlyOK (51) (K(i) of 140 μM), which has the sequence matching that of the α1(I) chain of collagen in P1', P2', P3' after the cleavage site. Several compounds were prepared in an attempt to identify the nature of the S2', S3', and S4' binding sites. Alanine at the P2' position was replaced by leucine, phenylalanine, tryptophan, or tyrosine derivatives, resulting in K(i) values in a significantly lower range, 1.0-40 μM, compared to 51. No upper size limitation or specificity has been found at this position, yet similar replacements at the P3' position, which is occupied naturally by a glycine residue, gave weaker inhibitors: (EtO)(OK)P(O)-Ile-Tyr(OBzl)-PheOK (57) had a K(i) of 120 μM. Hexapeptide derivatives had weaker activities in the 270 μM-2 mM range. All inhibitors were evaluated by using the synthetic thio peptolide spectrophotometric assay.
