167102-63-8Relevant academic research and scientific papers
DEUTERATED O-SULFATED BETA-LACTAM HYDROXAMIC ACIDS AND DEUTERATED N-SULFATED BETA-LACTAMS
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Page/Page column 73, (2017/11/10)
Provided herein are deuterated O-sulfated beta-lactam hydroxamic acids and deuterated N-sulfated beta-lactams, pharmaceutical compositions thereof and methods of treating infectious disease with deuterated compounds or pharmaceutical compositions thereof.
Effects on polo-like kinase 1 polo-box domain binding affinities of peptides incurred by structural variation at the phosphoamino acid position
Qian, Wenjian,Park, Jung-Eun,Liu, Fa,Lee, Kyung S.,Burke Jr., Terrence R.
, p. 3996 - 4003 (2013/07/27)
Protein-protein interactions (PPIs) mediated by the polo-box domain (PBD) of polo-like kinase 1 (Plk1) serve important roles in cell proliferation. Critical elements in the high affinity recognition of peptides and proteins by PBD are derived from pThr/pS
Reactions of carbon nucleophiles with 2,2,3-trisubstituted ethynylaziridines
Kelley, Brandon T.,Joullie, Madeleine M.
, p. 1233 - 1239 (2013/10/22)
Carbon nucleophiles were used to open a 2,2,3-trisubstituted ethynylaziridine. A cyanide nucleophile opened the ring at the more substituted carbon, proceeding regioselectively with inversion of configuration. In an attempt to expand upon the scope of the reaction, Normant cuprates were reacted with a 2,2,3-trisubstituted ethynylaziridine. This reaction produced chiral allenes via an anti-SN2′ pathway. X-ray analysis of a derivative allowed the absolute stereochemistry of the anti-allenes to be assigned as P.
HETEROBICYCLIC COMPOUNDS AS BETA-LACTAMASE INHIBITORS
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Page/Page column 171; 172, (2013/10/22)
The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts, are useful in combination with beta-lactam antibiotics, or alone, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to formula (Ia): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R 2, R 3 and R 4 are described herein.
Synthetic studies on callipeltins: Stereoselective syntheses of (3S,4R)-3,4-dimethyl-L-pyroglutamic acid and fmoc-D-allothreonine from serine derivatives
Konno, Hiroyuki,Takebayashi, Yoko,Nosaka, Kazuto,Akaji, Kenichi
experimental part, p. 79 - 89 (2010/05/19)
The non-proteinogenic amino acids contained in callipeltins, (3S, 4R)-3, 4-dimefhyl-L-pyroglutamic acid and D-allothreonine, were synthesized from D- or L-serine. The stereoselective synthesis of two methyl groups of (3S, 4R)-3, 4-dimethyl-L-pyroglutamic acid was accomplished by diastereoselective hydrogenation and alkylation. Kinetic epimerization of the C-4 methyl substituent followed by Boc-deprotection with 10% TFA gave the desired (3S, 4R)-3, 4-dimethyl-L-pyroglutamic acid as a single isomer.
An improved method for culturing Streptomyces sahachiroi: Biosynthetic origin of the enol fragment of azinomycin B
Kelly, Gilbert T.,Sharma, Vasudha,Watanabe, Coran M.H.
, p. 4 - 15 (2008/09/21)
Azinomycin B is an environmental DNA crosslinking agent produced by the soil microorganism Streptomyces sahachiroi. While the agent displays potent cytotoxic activities against leukemic cell lines and animal mouse models, the lack of a consistent supply of the natural product has hampered detailed biological investigations on the compound, including its mode of action and biosynthesis. We report here a significant methodological improvement in the culturing of the bacterium, which allows reliable and steady production of the natural product in good yields. The key experimental step involves the culturing of the strain on dehydrated plates, followed by the generation of a two-stage starter culture and subsequent fermentation of the strain under nutrient-starved conditions. We illustrate use of this culture system by investigating the formation of the enol fragment of the molecule in isotopic labeling experiments with threonine and several advanced precursors (β-ketoamino acid 3, β-hydroxyamino aldehyde 4, and β-ketoaminoaldehyde 5). The results unequivocally show that threonine is the most advanced precursor accepted by the NRPS (non-ribosomal peptidyl synthetase) machinery for final processing and construction of the enol moiety of the natural product.
Evolution of the total syntheses of ustiloxin natural products and their analogues
Li, Pixu,Evans, Cory D.,Wu, Yongzhong,Cao, Bin,Hamel, Ernest,Joullie, Madeleine M.
, p. 2351 - 2364 (2008/09/20)
Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an SNAr reaction. An NOE study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F, and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R,10S)-epi-ustiloxin analogues) were prepared via the second-generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization.
The enantioselective synthesis of phomopsin B
Grimley, Joshua S.,Sawayama, Andrew M.,Tanaka, Hiroko,Stohlmeyer, Michelle M.,Woiwode, Thomas F.,Wandless, Thomas J.
, p. 8157 - 8159 (2008/09/18)
Proven approach to a family of antimitotics: The total synthesis of phomopsin B, an antimitotic natural product, was achieved by assembling two fragments of equal complexity in a longest linear sequence of 26 steps. The approach features two catalytic tra
Synthesis of trans-(3S)-Amino-(4R)-alkyl- and -(4S)-Aryl-piperidines via Ring-Closing Metathesis Reaction
Hu, X. Eric,Kim, Nick K.,Ledoussal, Benoit
, p. 4499 - 4502 (2007/10/03)
(Matrix Presented) trans-(3S)-Amino piperidines bearing various alkyl and aryl substituents at the C-4 position were synthesized via a ring-closing metathesis reaction. The absolute stereochemistry was controlled using a protected D-serine as a starting material. Stereoselective hydrogenation of allylamines provided trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines. This procedure presents the first method for the asymmetric synthesis of 4-substituted 3-amino piperidines.
Total synthesis of A-315675: A potent inhibitor of influenza neuraminidase
Hanessian, Stephen,Bayrakdarian, Malken,Luo, Xuehong
, p. 4716 - 4721 (2007/10/03)
A concise, stereocontrolled, and practical synthesis of a neuraminidase inhibitor consisting of a highly functionalized D-proline scaffold is described. Key features involve a stereocontrolled addition of a propiolate ester to a chiral nonracemic nitrone
