A practical synthesis of 1,3-disubstituted cubane derivatives

Kazi, Nahin; Aublette, Marine C.; Allinson, Sarah L.; Coote, Susannah C.

doi:10.1039/d3cc02164e

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…Cubanes have long been speculated to be the ideal benzene bioisostere, and recent advancements in novel synthetic strategies have broadened the scope of cubane substitution patterns for both organic and medicinal chemistry researchers . We included two cubane derivatives in our substrate scope as well ( 33a , 47% combined yield, 3:1 d.r.…”

Section: Resultsmentioning

confidence: 99%

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres

Ma,

Beard,

Burgess

et al. 2024

J. Org. Chem.

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Recent years have seen novel modalities emerge for the treatment of human diseases resulting in an increase in beyond rule of 5 (bRo5) chemical matter. As a result, synthetic innovations aiming to enable rapid access to complex bRo5 molecular entities have become increasingly valuable for medicinal chemists’ toolkits. Herein, we report the general synthesis of a new class of noncanonical amino acids (ncAA) with a cyclopropyl backbone to achieve conformational constraint and bearing C(sp 3)-rich benzene bioisosteres. We also demonstrate preliminary studies toward utilities of these ncAA as building blocks for medicinal chemistry research.

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Section: Resultsmentioning

confidence: 99%

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres

Ma,

Beard,

Burgess

et al. 2024

J. Org. Chem.

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“…B: Cross coupling reactions for derivatisations of 1,3-cubanes [ 51 ]. C: Coote and co-workers’ de novo synthesis of 1,3-cubanes [ 64 ]. D: Coote and co-workers’ derivatization of 1,3-cubanes [ 64 ].…”

Section: Reviewmentioning

confidence: 99%

“…C: Coote and co-workers’ de novo synthesis of 1,3-cubanes [ 64 ]. D: Coote and co-workers’ derivatization of 1,3-cubanes [ 64 ]. a Dowex 50W X8 resin was used as the proton source.…”

Section: Reviewmentioning

confidence: 99%

(Bio)isosteres of ortho- and meta-substituted benzenes

Diepers,

Walker

2024

Beilstein J. Org. Chem.

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Saturated bioisosteres of substituted benzenes offer opportunities to fine-tune the properties of drug candidates in development. Bioisosteres of para-benzenes, such as those based on bicyclo[1.1.1]pentane, are now very common and can be used to increase aqueous solubility and improve metabolic stability, among other benefits. Bioisosteres of ortho- and meta-benzenes were for a long time severely underdeveloped by comparison. This has begun to change in recent years, with a number of potential systems being reported that can act as bioisosteres for these important fragments. In this review, we will discuss these recent developments, summarizing the synthetic approaches to the different bioisosteres as well as the impact they have on the physiochemical and biological properties of pharmaceuticals and agrochemicals.

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“…However, nowadays compound 3a is commercially available as well as 4‐(methoxycarbonyl)cubane‐1‐carboxylic acid 3b . In addition, 3‐(methoxycarbonyl)cubane‐1‐carboxylic acid 3c [15–16] as well as 2‐(methoxycarbonyl)cubane‐1‐carboxylic acid 3d [16] were synthesized allowing an easy access to different cubane derivatives. It is worth mentioning that methyl cubane‐1‐carboxylate 3e can be obtained by decarboxylation of 3b [8] ( Figure 3).…”

Section: Introductionmentioning

confidence: 99%

Functionalization of Cubane Formation of C−C and C−Heteroatom Bonds

Yasukawa,

Håheim,

Cossy

2024

Helvetica Chimica Acta

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Functionalized cubanes are attractive scaffolds for medicinal chemists as they are bioisosteres of benzene rings. The replacement of a benzene ring by a cubane, in a bioactive compound, can have a beneficial effect on the biological activity of such compound. Thus, the design of new molecular cubyl building blocks is of importance. In this review, we will focus on the functionalization of cubanes by creating C−C, C−heteroatom bonds e. g. C−N, C−O, C−B, C−P and C−S bonds. Different methods are reported involving organometallics, radicals, and ionic species. Mechanisms are included when relevant.

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A practical synthesis of 1,3-disubstituted cubane derivatives

Abstract: A robust multigram-scale synthesis of 1,3-disubstituted cubanes (previously only available on milligram-scale) is reported. The synthesis exploits a readily available enone intermediate that has previously been used for the synthesis...

Cited by 11 publications

References 22 publications

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres

(Bio)isosteres of ortho- and meta-substituted benzenes

Functionalization of Cubane Formation of C−C and C−Heteroatom Bonds

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A practical synthesis of 1,3-disubstituted cubane derivatives

Abstract: A robust multigram-scale synthesis of 1,3-disubstituted cubanes (previously only available on milligram-scale) is reported. The synthesis exploits a readily available enone intermediate that has previously been used for the synthesis...

Cited by 11 publications

References 22 publications

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp3)-Rich Benzene Bioisosteres

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp3)-Rich Benzene Bioisosteres

(Bio)isosteres of ortho- and meta-substituted benzenes

Functionalization of Cubane Formation of C−C and C−Heteroatom Bonds

Contact Info

Product

Resources

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General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp³)-Rich Benzene Bioisosteres