76110-78-6

Upstream product

• 18680-27-8 pinanediol 
• 98-80-6 phenylboronic acid 
• 24388-23-6 2-phenyl-4,4,5,5-tetramethyl-1,3,2-dioxoborole 
• 1061180-99-1 (4R,5R)-diisopropyl-2-phenyl-1,3,2-dioxaborolane-4,5-dicarboxylate 
• 1061181-00-7 (-)-4,5-dimethyl-2-phenyl[1.3.2]dioxaborolane 
• 1692-26-8 bis(propan-2-yl) phenylboronate 
• 7785-70-8 (+)-α-pinene 

Downstream Products

• 76110-79-7 (S)-(chloro(phenyl)methyl)boronic acid boronic acid (1S,2S,3R,5S)-(+)-2,3-pinanediol ester 
• 85922-61-8 (+)-pinanediol (αR)-α-chlorobenzylboronate 
• 497258-69-2 (+)-pinanediol (1R)-1-(2-thienylacetylamino)-1-phenylmethylboronate 
• 78922-83-5 (1-phenylmethyl)boronic acid (1S,2S,3R,5S)-(+)-2,3-pinanediol ester 
• 76110-80-0 (+)-pinanediol (S)-1-phenylethane-1-boronate 
• 78902-03-1 1-(S)-chloro-2-phenylethylboronic acid (1S,2S,3R,5S)-(+)-pinane-2,3-glycol ester 
• 476334-31-3 (R)-(1-amino-1-phenylmethyl)boronic acid (1S,2S,3R,5S)-(+)-2,3-pinanediol ester hydrochloride salt 

Relevant academic research and scientific papers

Examination of pinanediol-boronic acid ester formation in aqueous media: Relevance to the relative stability of trigonal and tetrahedral boronate esters

The interaction of pinanediol with 2-fluorophenylboronic acid and several other substituted phenylboronic acids was studied in 40% vol. aqueous acetonitrile by 1H and 11B NMR, potentiometric and spectrophotometric titrations at variable pH values. The experimental results reveal the formation of a very stable trigonal ester (Ktrig ≈ 2 × 104 M-1) and a significantly less stable tetrahedral hydroxocomplex (Ktet ≈ 5 × 103 M-1) in contrast to the traditionally observed inverted order of stabilities Ktrig tet. Comparison of the crystal structure of the trigonal ester isolated from aqueous acetonitrile with the DFT simulated structure of the respective hydroxocomplex shows that an unusual order of stabilities Ktrig > Ktet is observed in spite of the existence of the usual strain release effect in the O-B-O angle considered responsible for the typically observed increased stability of the tetrahedral hydroxocomplex. A complementary study of the stability of the six-membered cyclic boronate esters of chromotropic acid demonstrated the order Ktrig ? Ktet although the strain was absent in these esters. The results for m-, p-substituted phenylboronic acids show that the stability of both five- and six-membered trigonal esters formed with pinanediol and chromotropic acid, respectively, is insensitive to electronic effects but the electron accepting substituents stabilize the hydroxocomplexes. It follows from the whole set of results that Ktet can be much larger than Ktrig in the absence of the strain, but with a sufficiently acidic diol, and that the presence of the strain does not necessarily make Ktet larger than Ktrig for a less acidic diol with a purely saturated hydrocarbon backbone. Thus, the electronic effects manifested in the acidity of the diol appear to be more significant than the strain release effect in determining the Ktet/Ktrig ratio.

Mercapto-amide boronic acid derivative and application thereof as MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase) inhibitor

The invention provides a compound of a formula (I) shown in the specification, or a conformational isomer, or an optical isomer or a pharmaceutically acceptable salt thereof. The compound of the formula (I) shown in the specification has excellent broad-spectrum inhibitory activity on MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase), and can be used for preparing MBL and/or SBL inhibitors. Moreover, the compound disclosed by the invention has excellent antibacterial activity on multiple drug-resistant bacteria and is capable of reversing drug resistance of carbapenem drug-resistant bacteria, and the antibacterial effect of the compound is prior to those of positive control products such as L-captopril and tazobactam. The compound disclosed by the invention has very great potential in preparation of MBL/SBL dual inhibitors and medicines reversing drug resistance of carbapenem drug-resistance bacteria.

Structure-based development of (1-(3′-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- And Serine-β-lactamases

The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.

Design, synthesis and docking studies of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα- and αβ-amino acids

A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα- and αβ-amino acids were designed and synthesized. Their structures were elucidated by 1H NMR, 13C NMR, LC-MS and HRMS. These compounds were evaluated for their β5 subunit inhibitory activities of human proteasome. The results showed that dipeptidyl boronic acid inhibitors composed of αα-amino acids were as active as bortezomib. Interestingly, the activities of those derived from αβ-amino acids lost completely. Of all the inhibitors, compound 22 (IC50 = 4.82 nM) was the most potent for the inhibition of proteasome activity. Compound 22 was also the most active against three MM cell lines with IC50 values less than 5 nM in inhibiting cell growth assays. Molecular docking studies displayed that 22 fitted very well in the β5 subunit active pocket of proteasome.

Iron catalysis and water: A synergy for refunctionalization of boron

A new catalytic system has been optimized to promote the conversion of boron species into others. FeCl3 associated with imidazole and water favors boron refunctionalization under mild conditions. Georg Thieme Verlag Stuttgart New York.

A comparative study of the relative stability of representative chiral and achiral boronic esters employing transesterification

A comparative study of the transesterification of five representative chiral and achiral boronic esters with various structurally modified diols was undertaken to qualitatively understand the factors influencing the relative stability of these boronic esters. Several factors such as chelation, conformation, steric bulk of the substituents, size of the heterocycle, and entropy influence the relative rate of transesterification as well as the stability of the boronic esters. Amongst these boronic esters, pinanediol phenylboronic ester was found to be the most stable boronic ester whereas DIPT boronic ester appeared to be thermodynamically the least stable one. The transesterification with sterically hindered diols was observed to be relatively slow, but afforded thermodynamically more stable boronic esters. Boronic esters derived from cis-cyclopentanediols and the bicyclo[2.2.1]heptane-exo,exo-2,3- diols are relatively more stable. This study not only presents the qualitative picture of relative stability of various boronic esters, but also provides helpful hints regarding the possible recovery of chiral auxiliaries. Many C 2-symmetric chiral auxiliaries, such as 2,3-butanediol, 2,4-pentanediol, DIPT, and cis-cyclohexane-1,2-diol, can be retrieved by simple transesterification of the corresponding boronic esters with commercial inexpensive diols, such as pinacol, 1,3-propanediol, and neopentyl glycol.

Expanding the scope of PNA-encoded libraries: divergent synthesis of libraries targeting cysteine, serine and metallo-proteases as well as tyrosine phosphatases

Seven PNA-encoded combinatorial libraries targeting proteases and phosphatases with covalent reversible and irreversible mechanism-based inhibitors were prepared. The libraries were synthesized using modified PNA monomers, which dramatically increase the water solubility of the libraries in biologically relevant buffers. The libraries were shown to selectively inhibit targeted enzymes.

Nanomolar β-lactamase inhibitors

New carboxyphenyl-glycylboronic acid transition-state analog inhibitors, representative of a class of compounds effective against class C β-lactamase AmpC. The new compounds improve inhibition by over two-orders of magnitude compared to analogous glycylboronic acids, with Ki values as low as 1 nM.

Nanomolar inhibitors of AmpC β-lactamase

β-lactamases are the most widespread resistance mechanism to β-lactam antibiotics, such as the penicillins and the cephalosporins. In an effort to combat these enzymes, a combination of stereoselective organic synthesis, enzymology, microbiology, and X-ra

Asymmetric alkyldifluoroboranes and their use in secondary amine synthesis

(matrix presented) Asymmetric diol boronic esters with potassium bifluoride form the corresponding alkyltrifluoroborate and free diol under mild conditions. Defluoridation with tetrachlorosilane produces an alkyldifluoroborane intermediate. This conversio