Modular Synthesis of β-Amino Boronate Peptidomimetics

Kaldas, Sherif J.; Rogova, Tatiana; Nenajdenko, Valentine G.; Yudin, Andrei K.

doi:10.1021/acs.joc.8b00325

Cited by 24 publications

(21 citation statements)

References 38 publications

(31 reference statements)

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“…Our studies go much beyond a singleton report on the use of a few free boronic acids in the Ugi reaction as we also investigated the GBB-3CR, UT-4CR, and several different IMCR variations more in an unprecedented breadth of building block combinations ( 35 , 36 ). In other reports, isocyanide-bearing boronic acids are only known in their protected ester form that would need another, often harsh, deprotecting step to yield boronic acids suitable for screening ( 39 , 40 ). Here, we found that IMCR generally runs under such mild conditions that free boronic acids are widely tolerated.…”

Section: Resultsmentioning

confidence: 99%

Rapid approach to complex boronic acids

et al. 2019

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The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing–enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.

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Section: Resultsmentioning

confidence: 99%

Rapid approach to complex boronic acids

et al. 2019

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“…Besides reduction with NaBH(OAc) 3 , iminium ion 31 could be engaged in the Ugi four‐component reaction (Scheme 21, eq. 2) [61] or a Strecker‐type transformation (Scheme 21, eq. 3) [62] to access β‐amino MIDA boronates.…”

Section: Methods For the Synthesis Of β‐Aminoalkylboronic Acid Derivativesmentioning

confidence: 99%

Synthesis and Applications of β‐Aminoalkylboronic Acid Derivatives

Hall

2020

Adv Synth Catal

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α‐Aminoalkylboronic acids display a distinct role in medicinal chemistry, and their utility has been demonstrated by the successful commercialization of three drugs: bortezomib, ixazomib, and vaborbactam. Just as α‐aminoalkylboronic acids are a bioisostere of α‐amino acids, β‐aminoalkylboronates are a bona fide bioisostere of β‐amino acids, thus they also hold promising potential in drug discovery. Moreover, β‐aminoalkylboronates are versatile synthetic intermediates that are amenable to many of the established C−B bond derivatization reactions of chiral optically enriched alkylboronates, leading to the stereocontrolled preparation of valued classes of products such as β‐amino alcohols, 1,2‐diamines, and hemiboronic acid heterocycles. In addition, β‐aminoalkylboronates were shown to act as catalysts in certain organic reactions. This review presents an overview of the strengths and limitations of current preparative methods to access β‐aminoalkylboronic acid derivatives stereoselectively with various substitution patterns. Strategically, several disconnections can be exploited to establish both functional groups. Some of the key methods include the classical Matteson asymmetric homologation chemistry, transition metal‐catalyzed aminoboration of alkenes and formal hydroboration of enamine derivatives, nucleophilic additions of boryl‐substituted carbanions onto N‐functionalized imines, borylative ring openings of aziridines, and functionalization of alpha‐boryl aldehydes.

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“…Said review attested to the rapid development in the field, with most of the protocols having been reported in the literature over the last decade. Even if major advances regarding the synthetic accessibility of such derivatives have been made, most of the reported strategies still rely on multi-step sequences, though there is a single example of a multicomponent strategy [15]. Owing to their ability to construct highly functionalized molecular scaffolds from simple precursors in a single step, multicomponent reactions (MCRs) can be considered excellent tools for diversity-oriented synthesis applications in the drug discovery field [16].…”

Section: Introductionmentioning

confidence: 99%

Isonitrile-Based Multicomponent Synthesis of β-Amino Boronic Acids as β-Lactamase Inhibitors

et al. 2020

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The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study.

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Modular Synthesis of β-Amino Boronate Peptidomimetics

Cited by 24 publications

References 38 publications

Rapid approach to complex boronic acids

Rapid approach to complex boronic acids

Synthesis and Applications of β‐Aminoalkylboronic Acid Derivatives

Isonitrile-Based Multicomponent Synthesis of β-Amino Boronic Acids as β-Lactamase Inhibitors

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