76110-79-7

Upstream product

• 75-09-2 dichloromethane 
• 76110-78-6 (3aS,4S,6S,7aR)-3a,5,5-trimethyl-2-phenylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole 
• 2146-67-0 (dichloromethyl)lithium 
• 18680-27-8 pinanediol 
• 98-80-6 phenylboronic acid 

Downstream Products

• 76110-80-0 (+)-pinanediol (S)-1-phenylethane-1-boronate 
• 85922-61-8 (+)-pinanediol (αR)-α-chlorobenzylboronate 
• 476334-31-3 (R)-(1-amino-1-phenylmethyl)boronic acid (1S,2S,3R,5S)-(+)-2,3-pinanediol ester hydrochloride salt 
• 497258-69-2 (+)-pinanediol (1R)-1-(2-thienylacetylamino)-1-phenylmethylboronate 

Relevant academic research and scientific papers

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.

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

P1 Phenethyl peptide boronic acid inhibitors of HCV NS3 protease

A series of peptide boronic acids containing extended, hydrophobic P1 residues was prepared to probe the shallow, hydrophobic S1 region of HCV NS3 protease. The p-trifluoromethylphenethyl P1 substituent was identified as optimal with respect to inhibitor potency for NS3 and selectivity against elastase and chymotrypsin.

(R,R)-2,3-butanediol as chiral directing group in the synthesis of (αS)-α-chloro boronic esters

(R,R)-2,3-Butanediol dichloromethane-boronate is a convenient reagent for attaching a chiral carbon to a Grignard or lithium reagent via zinc chloride catalyzed rearrangment of the intermediate borate complex, which yields (αS)-α-chloro boronic esters with 91-96% diastereoselectivity. The esters are easily hydrolyzed to crystalline boronic acids.

Epimerization of α-chloro boronic esters by lithium and zinc chlorides

The epimerization of (+)-pinanediol (αS)-α-chloro-α-phenylmethaneboronate (3) to the (αR)-isomer 4 is catalyzed by lithium chloride in tetrahydrofuran (THF). The rate is first-order in 3 and approximately 0.75 order in lithium chloride over the range 0.04

Directed chiral synthesis by way of α-chloro boronic esters

Homologation of (+)-pinanediol boronic esters, RBO2C10H16, with (dichloromethyl)lithium has yielded αS α-chloro boronic esters, RCHClBO2C10H16, in diastereomeric purities from 74% (R = CH3) to 98% (R = C6H5), with typical alkyl groups (n-butyl, cyclohexyl) ranging from 83 to 90%. Grignard or lithium reagents replace the α-chloro function by alkyl with inversion. Peroxidic oxidation of the residing boronic esters proceeds with retention of configuration to yield alcohols of known rotation and absolute configuration. Purification of (+)-pinanediol to 100% enantiomeric excess (ee) was accomplished by way of recrystallization of sodium bis(pinanediol) borate, which on acidification yields a 1:1 mixture of pinanediol and pinanediol boric acid ester, not freed from boron but used directly to make pinanediol boronic esters of 100% ee. The synthetic utility of these processes was demonstrated by highly stereoselective and efficient synthesis of (2S,3S-3-phenyl-2-butanol and (2R,3S)-3-phenyl-2-butanol. The latter synthesis involved construction of the first chiral center from (+)-pinanediol phenylboronate, cleavage of the (+)-pinanediol with boron trichloride and replacement by (-)-pinanediol, and then introduction of the second chiral center.