Rapid approach to complex boronic acids

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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The Fifth Element in Drug Design: Boron in Medicinal Chemistry

Australian Journal of Chemistry ◽

10.1071/ch13256 ◽

2013 ◽

Vol 66 (10) ◽

pp. 1118 ◽

Cited By ~ 30

Author(s):

Jan Kahlert ◽

Christopher J. D. Austin ◽

Michael Kassiou ◽

Louis M. Rendina

Keyword(s):

Pharmaceutical Industry ◽

Drug Design ◽

Boronic Acid ◽

Medicinal Chemistry ◽

Building Blocks ◽

New Drugs ◽

Great Promise ◽

Research Groups ◽

Innovative Drug ◽

Boronic Acid Derivatives

The unique chemistry of boron allows for the utilisation of novel building-blocks which are not traditionally found in medicinal chemistry. The pharmaceutical industry has begun to exploit boronic acid derivatives as new drugs and several research groups are also exploring 1,2-azaborines and icosahedral boranes known as carboranes as boron-based structural motifs, with great promise for innovative drug design. Recent advances in the medicinal chemistry of these three important boron moieties are highlighted and illustrated with selected examples.

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Synthesis and Optoelectronic Characterization of Perylene Diimide-Quinoline Based Small Molecules

Molecules ◽

10.3390/molecules24234406 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4406 ◽

Cited By ~ 5

Author(s):

Stefania Aivali ◽

Loukia Tsimpouki ◽

Charalampos Anastasopoulos ◽

Joannis K. Kallitsis

Keyword(s):

Small Molecules ◽

Energy Levels ◽

Visible Spectrum ◽

Suzuki Coupling ◽

Building Blocks ◽

Fine Tuning ◽

Perylene Diimide ◽

Type Semiconductor ◽

Boronic Acid Derivatives

Perylene diimide (PDI) is one of the most studied functional dyes due to their structural versatility and fine tuning of the materials properties. Core substituted PDIs are prominent n-type semiconductor materials that could be used as non-fullerene acceptors in organic photovoltaics. Herein, we develop versatile organic building blocks based on PDI by decorating the PDI core with quinoline groups. Styryl and hydroxy phenyl mono and difunctionalized molecules were prepared using mono-nitro and dibromo bay substituted PDIs by Suzuki coupling with the respective boronic acid derivatives. A novel methodology using nitro-PDI under Suzuki coupling conditions as an electrophile partner was successfully tested. Furthermore, the PDI derivatives were used for the synthesis of soluble, electron accepting small molecules combining PDI with weak electron withdrawing quinoline derivatives. The new molecules presented wide absorbance in the visible spectrum from 450 to almost 700 nm while their LUMO levels and their energy levels are in the range of −3.8 to −4.2 eV.

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Synthesis of Sugar–Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy

Organic Letters ◽

10.1021/acs.orglett.7b00382 ◽

2017 ◽

Vol 19 (7) ◽

pp. 1678-1681 ◽

Cited By ~ 8

Author(s):

Daniela Imperio ◽

Erika Del Grosso ◽

Silvia Fallarini ◽

Grazia Lombardi ◽

Luigi Panza

Keyword(s):

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Boronic Acid ◽

Neutron Capture Therapy ◽

Boron Neutron Capture ◽

Boronic Acid Derivatives

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2-(6-Bromopyridin-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and (6-bromopyridin-3-yl)boronic acid, new bifunctional building blocks for combinatorial chemistry

Acta Crystallographica Section C Crystal Structure Communications ◽

10.1107/s0108270103000908 ◽

2003 ◽

Vol 59 (3) ◽

pp. o111-o113 ◽

Cited By ~ 8

Author(s):

Jana Sopková-de Oliveira Santos ◽

Jean-Charles Lancelot ◽

Alexandre Bouillon ◽

Sylvain Rault

Keyword(s):

Combinatorial Chemistry ◽

Boronic Acid ◽

Building Blocks

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Droplet-Assisted Microfluidic Fabrication and Characterization of Multifunctional Polysaccharide Microgels Formed by Multicomponent Reactions

Polymers ◽

10.3390/polym10101055 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1055 ◽

Cited By ~ 14

Author(s):

Nicolas Hauck ◽

Nalin Seixas ◽

Silvia Centeno ◽

Raimund Schlüßler ◽

Gheorghe Cojoc ◽

...

Keyword(s):

Hyaluronic Acid ◽

Multicomponent Reactions ◽

Building Blocks ◽

Correlation Spectroscopy ◽

Droplet Microfluidics ◽

Phase Imaging ◽

Colloidal Probe ◽

Young’S Moduli ◽

Depth Analysis ◽

The Impact

Polysaccharide-based microgels have broad applications in multi-parametric cell cultures, cell-free biotechnology, and drug delivery. Multicomponent reactions like the Passerini three-component and the Ugi four-component reaction are shown in here to be versatile platforms for fabricating these polysaccharide microgels by droplet microfluidics with a narrow size distribution. While conventional microgel formation requires pre-modification of hydrogel building blocks to introduce certain functionality, in multicomponent reactions one building block can be simply exchanged by another to introduce and extend functionality in a library-like fashion. Beyond synthesizing a range of polysaccharide-based microgels utilizing hyaluronic acid, alginate and chitosan, exemplary in-depth analysis of hyaluronic acid-based Ugi four-component gels is conducted by colloidal probe atomic force microscopy, confocal Brillouin microscopy, quantitative phase imaging, and fluorescence correlation spectroscopy to elucidate the capability of microfluidic multicomponent reactions for forming defined polysaccharide microgel networks. Particularly, the impact of crosslinker amount and length is studied. A higher network density leads to higher Young’s moduli accompanied by smaller pore sizes with lower diffusion coefficients of tracer molecules in the highly homogeneous network, and vice versa. Moreover, tailored building blocks allow for crosslinking the microgels and incorporating functional groups at the same time as demonstrated for biotin-functionalized, chitosan-based microgels formed by Ugi four-component reaction. To these microgels, streptavidin-labeled enzymes are easily conjugated as shown for horseradish peroxidase (HRP), which retains its activity inside the microgels.

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