The University of Tokyo · Medicine
Professor Junichiro Kanazawa's research lab specializes in the development of novel synthetic methodologies for three-dimensional, strained organic scaffolds—particularly bicyclo[1.1.1]pentane (BCP) and bicyclo[3.1.1]heptane (BCH)—to serve as bioisosteres in drug discovery. The lab focuses on enabling efficient functionalization of these rigid, cage-like frameworks to improve drug-like properties such as permeability, solubility, and metabolic stability. A key innovation involves the use of radical chemistry and cross-coupling reactions at sterically congested sp³ carbon centers, including pioneering work on silaboration and Suzuki-Miyaura coupling on BCP. The lab also explores the chemistry of monocarba-closo-dodecaborate anions, leveraging their unique stability and electronic properties for applications in medicinal chemistry and materials science.
Figures are computed from collected data and may differ slightly.
Three-dimensional, small-ring scaffolds are very important in modern drug discovery to expand the available drug-like chemical space and to optimize drug candidates. Among them, bicyclo[1.1.1]pentane (BCP) is regarded as a high-value bioisostere for a phenyl ring or tert-butyl group; it provides an option to generate drug-like molecules with good passive permeability, high aqueous solubility, and improved metabolic stability, though the lack of methodology to functionalize BCP remains a signific
Utilization of three-dimensional cyclic scaffolds is important in modern drug discovery, both to provide greater opportunities for optimizing drug candidates and to expand the available chemical space of drugs. Among these scaffolds, bicyclo[1.1.1]pentane (BCP) is a high-value bioisostere for 1,4-disubstituted phenyl rings, internal alkynes, and the tert-butyl group, generally offering high passive permeability, high water solubility, and improved metabolic stability. However, the lack of method
The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive-free conditions. The silaborated BCP can be obtained on a gram-scale in a single step without the need for column-chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C-B/C-Si bonds on the BCP scaffol
There is increasing interest in replacement of the planar aromatic rings of drug candidates with three-dimensional caged scaffolds in order to improve the physical properties, but bioisosteres of <i>meta</i>-substituted benzenes have remained elusive. We focused on the bicyclo[3.1.1]heptane (BCH) scaffold as a novel bioisostere of <i>meta</i>-substituted benzenes, anticipating that [3.1.1]propellane (<b>2</b>) would be a versatile precursor of diversely functionalized BCHs. Here, we describe a p
New couple: A cross-coupling reaction at the carbon vertex of a monocarba-closo-dodecaborate has been developed to allow efficient introduction of various aryl groups and other sp2/sp-hybridized carbon centers. A copper(I) complex facilitated the coupling process with a wide range of electrophiles at room temperature. The reaction was used to prepare a series of C-arylated carborane anion derivatives (see picture; B green, C blue), some of which showed androgen-receptor binding activity and also
This Concept article focuses on the rapid growth in studies of the chemistry of the monocarba-closo-dodecaborate(-) anion (C1 carborane anion). As one of the most stable anions known, the C1 carborane anion has been useful for exploring the chemistry of highly reactive cations. On the other hand, development of novel functional molecules utilizing the unique properties of C1 carborane anion (e.g., σ-aromaticity, rigid spherical skeleton) has progressed more slowly. The main reason for this is th
Abstract The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive‐free conditions. The silaborated BCP can be obtained on a gram‐scale in a single step without the need for column‐chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C−B/C−Si bonds on the BC
The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. T
A new family of Mg salts of carba-<italic>closo</italic>-dodecaborate was developed for Mg ion battery applications. Modification at the boron vertices drastically improves the solubility without compromising the chemical and redox stability.
A cross-coupling reaction of lithium species of monocarba-<i>closo</i>-dodecaborate {[<i>closo</i>-CHB<sub>11</sub>H<sub>11</sub>]<sup>–</sup>} at the carbon vertex under palladium catalysis was developed. The properties of a metal–carborate complex in a transmetalation step were important to achieve the cross-coupling process with aryl halides, and the use of lithiated monocarba-<i>closo</i>-dodecaborate was found to promote the carbon–carbon bond formation to provide a series of C-arylated mon
Kreuzkupplungen am Kohlenstoff-Eckzentrum eines Monocarba-closo-dodecaborats ermöglichen die effiziente Einführung verschiedener Arylgruppen und anderer über sp2/sp-hybridisierte Kohlenstoffzentren gebundener Substituenten. Ein Kupfer(I)-Komplex erleichtert die Umsetzung mit zahlreichen Elektrophilen bei Raumtemperatur. Die Reaktion lieferte eine Reihe C-arylierter Carboran-Anionen (siehe Bild; B grün, C blau), darunter auch an Androgen-Rezeptoren bindende Substanzen und solche mit mesogenen Eig
A cross-coupling reaction at the carbon vertex of a monocarba-closo-dodecaborate has been developed to allow introduction of various aryl groups and other sp2/sp-hybridized carbon centers. A copper(I) complex facilitated the coupling process with a wide range of electrophiles at room temperature. The reaction was successfully used to prepare a series of C-arylated caborane anion derivatives, some of which showed potent androgen-receptor binding activity and excellent mesogenic properties.
Abstract The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α‐cyclodextrin (α‐CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3‐diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non‐polar so
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Die Verkapselung von Bicyclo[1.1.1]pentanen (BCPs) in α-Cyclodextrin und neue Protokolle für die Deiodierungsreaktion von 1,3-Diiod-BCP zu [1.1.1]Propellan werden von Kazunori Miyamoto, Masanobu Uchiyama et al. in ihrer Zuschrift auf S. 2740 beschrieben. Die Kombination dieser Methoden ermöglicht die bedarfsgerechte Herstellung von [1.1.1]Propellan in verschiedenen (protischen/aprotischen/polaren/nicht-polaren) Lösungsmitteln unter milden Bedingungen. Die Verkapselung von Bicyclo[1.1.1]pentanen
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