179324-69-7Relevant articles and documents
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo
Ju, Yuan,He, Lihui,Zhou, Yuanzheng,Yang, Tao,Sun, Ke,Song, Rao,Yang, Yang,Li, Chengwei,Sang, Zitai,Bao, Rui,Luo, Youfu
, p. 3104 - 3119 (2020/03/04)
Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of Staphylococcus aureus infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of SaClpP function. A time-saving and cost-efficient strategy integrating in silico position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure-activity relationships. Five of 150 compounds from the miniaturized synthesis exhibited improved inhibitory activity. Compound 43Hf was the most active inhibitor and showed reversible covalent binding to SaClpP while did not destabilize the tetradecameric structure of SaClpP. The crystal structure of 43Hf-SaClpP complex provided mechanistic insight into the covalent binding mode of peptidomimetic boronate and SaClpP. Furthermore, 43Hf could bind endogenous ClpP in S. aureus cells and exhibited significant efficacy in attenuating S. aureus virulence in vitro and in vivo.
Asymmetric Synthesis of α-Aminoboronates via Rhodium-Catalyzed Enantioselective C(sp3)-H Borylation
Reyes, Ronald L.,Sato, Miyu,Iwai, Tomohiro,Sawamura, Masaya
, p. 589 - 597 (2020/01/22)
α-Aminoboronic acids, isostructural boron analogues of α-amino acids, have received much attention because of the important biomedical applications implicated for compounds containing this structure. Additionally, the inherent versatility of α-aminoboronic acids as synthetic intermediates through diverse carbon-boron bond transformations makes the efficient synthesis of these compounds highly desirable. Here, we present a Rh-monophosphite chiral catalytic system that enables a highly efficient enantioselective borylation of N-adjacent C(sp3)-H bonds for a range of substrate classes including 2-(N-alkylamino)heteroaryls and N-alkanoyl- or aroyl-based secondary or tertiary amides, some of which are pharmaceutical agents or related compounds. Various stereospecific transformations of the enantioenriched α-aminoboronates, including Suzuki-Miyaura coupling with aryl halides and the Rh-catalyzed reaction with an isocyanate derivative of α-amino acid, affording a new peptide chain elongation method, have been demonstrated. As a highlight of this work, the borylation protocol was successfully applied to the catalyst-controlled site-selective and stereoselective C(sp3)-H borylation of an unprotected dipeptidic compound, allowing remarkably streamlined synthesis of the anti-cancer drug molecule bortezomib and offering a straightforward route for the synthesis of privileged molecular architectures.
PROCESS FOR PREPARING BORTEZOMIB, INTERMEDIATES, AND CRYSTALLINE FORMS THEREOF
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Paragraph 0043, (2020/05/29)
The present disclosure provides a process for preparing Bortezomib, intermediates, and crystalline forms thereof.
Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids
Hinkes, Stefan P.A.,Klein, Christian D.P.
, p. 3048 - 3052 (2019/05/10)
Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.
Rhodium-catalyzed regiodivergent and enantioselective hydroboration of enamides
Bai, Xiao-Yan,Zhao, Wei,Sun, Xin,Li, Bi-Jie
, p. 19870 - 19878 (2019/12/25)
Chiral α- and β-aminoboronic acids exhibit unique biological activities. General methods for the synthesis of these bioisosteres of amino acids are highly desirable. We report a facile preparation of these compounds through rhodium-catalyzed regiodivergent and enantioselective hydroboration of enamides. Catalytic asymmetric synthesis of α- and β-aminoboronic esters with high regio-, diastereo-, and enantioselectivities were achieved through effective catalyst control and tuning substrate geometry. Starting from easily available materials this strategy provides a unified synthetic access to both enantioenriched α-boration and β-boration products. The synthetic utility of these methods was demonstrated by efficient synthesis of an anticancer drug molecule and diverse transformations of the boration products.
Preparation method of bortezomib synthesis intermediate
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, (2020/02/10)
The present invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a preparation process of a bortezomib synthesis intermediate (R) 1-amino-3-methylbutyl boronic acid pinacol ester hydrochloride. The preparation
AN IMPROVED PROCESS FOR THE PREPARATION OF BORONIC ACID ESTERS
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, (2018/09/12)
The present invention relates to an improved process for the preparation of a compound of formula (I), wherein PG1 may be independently selected from tert-butyloxycarbonyl (Boc), phthaloyl, 9-fluorenylmethyloxycarbonyl (Fmoc), triphenylmethyl (Trityl), carboxybenzyl (Cbz), trifluoroacetyl, benzyl (Bn), benzylidene, methanesulfonyl (Mesyl), toluene sulfonyl (Tosyl) or acyl; its isolation as solid and use for the preparation of the compound of formula (IV), in particular the compound of formula (IV) i.e. [(1R)-3-methyl-1[[(2S)-1-oxo-3-phenyl-2- [(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid with more than 99.95% chiral purity, as measured by HPLC.
A solid-phase approach for the synthesis of α-Aminoboronic acid peptides
Daniels, Blake E.,Stivala, Craig E.
, p. 3343 - 3347 (2018/02/06)
A solid-phase synthesis of α-Aminoboronic acid peptides using a 1-glycerol polystyrene resin is described. Standard Fmoc solid-phase peptide chemistry is carried out to construct bortezomib and ixazomib. This approach eliminates the need for liquid-liquid extractions, silica gel column chromatography, and HPLC purifications, as products are isolated in high purity after direct cleavage from the resin.
Method for preparing chiral amino acid ester and the boron for assists meters with the application in the synthesis of
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, (2019/02/02)
The present invention discloses intermediates of chiral alpha-amino boric acid esters, chiral alpha-amino boric acid esters and salts thereof, and key intermediates for the synthesis of bortezomib. The invention also discloses a preparation method for the intermediates of the alpha-amino boric acid esters, and a method for synthesis of the bortezomib by using chiral alpha-amino boric acid esters and salts thereof and using a convergent strategy. According to the present invention, the bortezomib synthesis process route is low in cost, key intermediates are low in production cost, and operations are simple, very easy for industrial production.
