Tohoku University · Chemistry
Professor Shota Nagasawa's research lab specializes in the development of novel synthetic methodologies for constructing rigid, three-dimensional carbocyclic frameworks—particularly caged hydrocarbons such as cubanes, cuneanes, and spirocyclic systems—aimed at creating bioisosteres of aromatic rings. The lab focuses on transition-metal-catalyzed C–H activation, group transfer reactions, and oxidative transformations to enable selective functionalization of these strained systems under mild conditions. A central theme is the application of these synthetic methods to access drug-like scaffolds that mimic pharmaceutically relevant aromatic motifs, such as those found in acetylsalicylic acid and coumarin, for use in medicinal chemistry. The lab also integrates biological evaluation and computational studies to assess the potential of these caged systems as replacements for traditional aromatic cores in drug discovery.
Figures are computed from collected data and may differ slightly.
Few methods allow for the direct conversion of cycloalkenes into cycloalkadienes with high chemo- and regioselectivity. Herein, we report a convenient one-pot process for this transformation that involves the unprecedented N-preferential group transfer of N-oxoammonium salts to cycloalkenes, followed by Cope elimination, to afford cycloalkadienes at room temperature and pressure.
A novel method of introducing an oxygen functionality into a cubane core was developed using a transition-metal-catalyzed directed acetoxylation methodology via C-H activation. The obtained compounds were derivatized into cubane analogues of pharmaceutically relevant structural motifs, namely, acetylsalicylic acid and coumarin motifs, which could potentially act as bioisosteres of these scaffolds.
We herein evaluate a biological applicability of 1,3-substituted cuneanes as an isostere of m-substituted benzenes based on its structural similarity. An investigation of a method to obtain 1,3-substituted cuneanes by selective isomerization of 1,4-substituted cubanes enables this attempt by giving a key synthetic step to obtain a cuneane analogs of pharmaceuticals having m-substituted benzene moiety. Biological evaluation of the synthesized analogs and in silico study of the obtained result rev
The first catalytic oxygenative allylic transposition of unactivated alkenes into enones has been developed using an oxoammonium salt as the catalyst. This reaction converts various tri- and trans-disubstituted alkenes into their corresponding enones with transposition of their double bonds at ambient temperature in good yields. The use of a less-hindered azaadamantane-type oxoammonium salt as the catalyst and a combination of two distinct stoichiometric oxidants, namely, iodobenzene diacetate a
We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
Abstract Recently, many saturated bioisosteres of the benzene ring have been developed, and their applications in drug development have been evaluated. Most of these bioisosteres are caged hydrocarbons, which have rigid skeletons and three-dimensional spaces. Recent efforts to synthesize these caged hydrocarbons have enabled access to multi-functionalized congeners that are expected to be (bio)isosteres of multi-functionalized benzenes. This short review summarizes recently reported methods for
Abstract Few methods allow for the direct conversion of cycloalkenes into cycloalkadienes with high chemo‐ and regioselectivity. Herein, we report a convenient one‐pot process for this transformation that involves the unprecedented N‐preferential group transfer of N ‐oxoammonium salts to cycloalkenes, followed by Cope elimination, to afford cycloalkadienes at room temperature and pressure.
A catalytic method for the C-H alkylation of cubanes is described. Some hydrogen atom transfer catalysts enable the direct abstraction of a hydrogen atom from the C-H bond of cubanes, followed by conjugate addition of the generated cubyl radicals to electron-deficient alkenes. Synthetic applications of the functionalization method developed are also described.
We describe an enantiocontrolled route to a versatile intermediate for the synthesis of highly functionalized clovane-type terpenoids. The synthetic route commenced with (<i>R</i>)-carvone, a commercially available and enantioenriched building block, and an oxygenative strategy was used to concisely access a clovane scaffold. One example of the versatility of the obtained intermediate was the formal synthesis of rumphellclovane E.
Herein, we describe an enantiospecific route to one enantiomer of a common decalin core that is present in numerous highly oxygenated terpenoids. This intermediate is accessed in eight steps from (<i>R</i>)-carvone, an inexpensive, enantioenriched building block, which can be elaborated to the desired bicycle through sequential Fe(III)-catalyzed reductive olefin coupling and Dieckmann condensation. The same synthetic route may be applied to (<i>S</i>)-carvone to afford the enantiomer of this com
The effect of temperature upon the toxicity of DDT to a sensitive and a resistant strain of houseflies has been determined over the range 5° to 35° C. Acetone and acetone plus light spray oil were used as solvents for topical application. Maximum toxicity resulted at approximately 10° C. When the synergist 1,1‐bis p‐chlorophenyl methyl carbinol (DMC) was added in 1: 1 ratio by weight, the resistance was mostly overcome and toxicity increased to the lowest temperature. Zusammenfassung DIE BEZIEHU
We herein disclose a method to obtain 1,3-substituted cuneane by selective isomerization of 1,4-substituted cubanes. The electronic property of the substituent strongly affects the isomerization ratio of 1,3-substituted cuneane and 2,6-substituted cuneane. Based on structural similarity, we considered that 1,3-substituted cuneane would be a bioisostere of m-substituted benzene. The synthesis of a cuneane analog of pharmaceuticals having m-substituted benzene moiety and its biological evalu-ation
We herein disclose a method to obtain 1,3-substituted cuneane by selective isomerization of 1,4-substituted cubanes. The electronic property of the substituent strongly affects the isomerization ratio of 1,3-substituted cuneane and 2,6-substituted cuneane. Based on structural similarity, we considered that 1,3-substituted cuneane would be a bioisostere of m-substituted benzene. The synthesis of a cuneane analogs of pharmaceuticals having m-substituted benzene moiety and its biological and in sil
A method for C–H alkylation of cubanes is described herein. A hydrogen atom–transfer catalyst enables direct abstraction of a hydrogen atom from the C–H bond of cubanes, followed by conjugate addition of the generated cubyl radicals to various Michael acceptors. Synthetic applications of the developed functionalization method are also described.
Herein we describe an aerobic intramolecular dearomative coupling reaction of phenols using a catalytic system with the combination of a chromium–salen (Cr–salen) complex and a nitroxyl radical. This novel catalytic system enables the construction of a spirocyclic dienone product, which is a potentially useful intermediate for the synthesis of various natural products such as alkaloids and phenylpropanoids from bisphenol in good yield under mild reaction conditions (under O2 and ambient temperat
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