Synthesis of Thrombin Inhibitor DuP 714

Wityak, John; Earl, Richard A.; Abelman, Matthew M.; Bethel, Yvonne B.; Fisher, Barbara N.; Kauffman, Goss S.; Kettner, Charles A.; Ma, Philip; McMillan, Janice L.

doi:10.1021/jo00117a024

Cited by 71 publications

(42 citation statements)

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“…(This approach is one step longer than direct esterification with pinanediol, but loss of precious pinanediol is avoided.) Coupling reactions were performed as in the literature (21) to obtain compound 6, and in the case where the boronic acid 7 was wanted, deprotection was performed using either transesterification with phenyl boronic acid (22) or simple hydrolysis in water with hydrochloric acid. Compound 3 was then reacted with a Grignard reagent to obtain the substituted 2-azidoethyl boronates 4 with opposite stereochemistry, in high yield.…”

Section: Resultsmentioning

confidence: 99%

“…Reduction to the amine hydrochorides 5 was high-yielding reactions using standard techniques. Coupling reactions were performed as in the literature (21) to obtain compound 6, and in the case where the boronic acid 7 was wanted, deprotection was performed using either transesterification with phenyl boronic acid (22) or simple hydrolysis in water with hydrochloric acid.…”

Section: Resultsmentioning

confidence: 99%

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Boron‐Containing Peptidomimetics – A Novel Class of Selective Anti‐tubercular Drugs

et al. 2012

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Medical treatment for tuberculosis is complicated nowadays by the appearance of new multiresistant strains, and therefore, new antibiotics are in great need. Here, we report the synthesis and in vitro testing of a new class of highly selective antimicrobial boron-containing peptidomimetics with compounds exhibiting activity against Mycobacterium tuberculosis at ≤5 μg/mL. The new approach developed makes it possible to synthesize variously substituted β-aminoboronic acids and their derivatives with a high level of diastereoselectivity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Boron‐Containing Peptidomimetics – A Novel Class of Selective Anti‐tubercular Drugs

et al. 2012

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“…The conversion of pinanediol esters 15a,b to free boronic acids 16 and 17 was achieved through transesterification with phenylboronic acid in a biphasic acetonitrile/water system. 34 …”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Crystal Structures, and Antimicrobial Activity of Sulfonamide Boronic Acids as β-Lactamase Inhibitors

et al. 2010

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We investigated a series of sulfonamide boronic acids that resulted from the merging of two unrelated AmpC β-lactamase inhibitor series. The new boronic acids differed in the replacement of the canonical carboxamide, found in all penicillin and cephalosporin antibiotics, with a sulfonamide. Surprisingly, these sulfonamides had a highly distinct structure-activity relationship from the previously explored carboxamides, high ligand efficiencies (up to 0.91), Ki values down to 25 nM and up to 23 times better for smaller analogs. Conversely, Ki values were 10 to 20 times worse for larger molecules than in the carboxamide congener series. X-ray crystal structures (1.6–1.8 Å) of AmpC with three of the new sulfonamides suggest that this altered structure-activity relationship results from the different geometry and polarity of the sulfonamide versus the carboxamide. The most potent inhibitor reversed β-lactamase-mediated resistance to third generation cephalosporins, lowering their minimum inhibitory concentrations up to 32-fold in cell culture.

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“…However, in our hands, specific rotation of a (+)-pinanediol sample derived from Aldrich CAS Number 18680-27-8, under the same conditions as those used by Japanese authors [46], was +0.95. Much better agreement was observed in toluene, where the optical rotations of 7 were +8.5 to +7.9 [49][50][51]. In ethanol, in turn, these values vary between +2.8 and +3.3 [52][53][54].…”

Section: Exact Spatial Structure Determination Of Other Vic-diolsmentioning

confidence: 93%

Complementarity of electronic and vibrational circular dichroism based on stereochemical studies of vic-diols

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Górecki

Masnyk

et al. 2015

TrAC Trends in Analytical Chemistry

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Synthesis of Thrombin Inhibitor DuP 714

Cited by 71 publications

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Boron‐Containing Peptidomimetics – A Novel Class of Selective Anti‐tubercular Drugs

Boron‐Containing Peptidomimetics – A Novel Class of Selective Anti‐tubercular Drugs

Design, Synthesis, Crystal Structures, and Antimicrobial Activity of Sulfonamide Boronic Acids as β-Lactamase Inhibitors

Complementarity of electronic and vibrational circular dichroism based on stereochemical studies of vic-diols

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