Synthesis
DOI: 10.1055/a-2403-1860
short review
Bioisosteres

Cuneanes as Potential Benzene Bioisosteres Having Chirality

Hiyori Takebe
a   Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan
b   Mitsui Chemicals & Kyoto University Digital Chemical Laboratory, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan
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b   Mitsui Chemicals & Kyoto University Digital Chemical Laboratory, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan
c   Institute for Liberal Arts and Science, Kyoto University, Yoshida-Nihonmatsu, Sakyo, Kyoto 606-8510, Japan
› Author Affiliations
The authors are grateful for financial support from the Japan Society for the Promotion of Science (JSPS), KAKENHI (23H02605, 21H05233, and DC1 research fellowship 23KJ1339 to H.T.) and the Japan Science and Technology Agency (JST) (JPM-JMS522362 to S.M).


Abstract

Cuneane, a structural isomer of cubane, possesses C 2v symmetry, unlike the Oh symmetry of cubane. It can exhibit chirality with only a single substituent, differentiating it from cubane. Consequently, cuneane is being explored as a potential benzene bioisostere in pharmaceutical molecules, adding complexity such as chirality through isomerization of the cubane skeleton. Although there has been limited research on the synthesis of cuneane, recent years have seen increased attention devoted to this cage hydrocarbon. In this short review, we will discuss recent advances in the synthesis, utilization, and transformations of the cuneane framework into other cage hydrocarbons.

1 Introduction: Absolute Configuration Notation

2 Preparation of 1,3- and 2,6-Disubstituted Cuneanes by Constitutional Isomerization of 1,4-Disubstituted Cubanes

3 Preparation of 1,2-Disubstituted Cuneanes from 1-Cuneanecarboxamide via Directed ortho-Metalation

4 Investigation of the Potential as a Benzene Bioisostere

5 Asymmetric Synthesis of Cuneanes

6 Cuneane Scaffold Editing

7 Conclusion



Publication History

Received: 19 July 2024

Accepted after revision: 26 August 2024

Accepted Manuscript online:
26 August 2024

Article published online:
23 September 2024

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