Project Details
Description
Project Summary/Abstract
The long-term goal of my research laboratory is to establish strategies that allow the synthesis of previously
inaccessible regio-/stereodefined organoborons to ultimately enable the lego-like construction of C(sp3)-rich
bioactive molecules and protein conjugates. Modular synthetic strategies using interchangeable building
blocks are expected to enable a generalized route to the targeted compound class which is crucial for
optimizing its biological activity. Orthogonally functionalized vinylic or aromatic halo-organoborons have
played a critical role in many modular synthetic routes to natural products. In contrast, strategies to
construct multifunctional and stereodefined acylborons/alkyl boron building blocks and their applications for
modular synthesis of C(sp3)-rich molecular scaffolds and bioconjugates remain underexplored. The
research projects described in this proposal will provide a platform to achieve the above broader goal by
establishing a versatile acylboron/alpha-hydroxy boron-based paradigm to open-up access to several
unique organoborons having broad applications in medicinal chemistry and chemical biology.
Acylborons represent an underexplored class of organoborons whose existence and remarkable synthetic
utility is beginning to emerge only recently. We previously reported an unsymmetrical diboron-based
approach to construct rare acylborons including the first example of an alpha,beta-unsaturated acyl boron.
Our recent preliminary data suggests that alpha,beta-unsaturated acyl borons and alpha-hydroxy borons
are powerful intermediates to access orthogonally functionalized, regio- and stereodefined organoborons.
Building upon our published work and preliminary data, we will develop general methods for synthesis and
application of several new types of multifunctional acylborons and alpha-hydroxy borons to ultimately
provide enantioenriched organoborons that would be difficult to prepare using existing methods. We will
demonstrate the unique benefit of these novel building blocks to install rare substitution patterns on
bioactive molecules and to enable a modular synthetic approach to chiral frameworks found in medicinally
important compounds. In a complementary research direction, we will develop a new class of mutually
orthogonal bioconjugation agents that are expected to allow i) simultaneous probing of multiple protein-
protein interactions and ii) preparation of homogeneous and stable bioconjugates.
Status | Active |
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Effective start/end date | 1/08/21 → 31/07/25 |
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