Pilot-Scale Production of Dimethyl 1,4-Cubanedicarboxylate

Falkiner, Michael J.; Littler, Stuart W.; McRae, Kenneth J.; Savage, G. Paul; Tsanaktsidis, John

doi:10.1021/op400181g

“…With ar ange of mono-and 1,4-disubstituted cubane derivatives (i.e., [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]i nh and the valence isomerization to COT derivatives could be explored. [Note:T here are at least 20 valence isomers with the general formula( CH) 8 ; [34] however,t he only interconversion of cubanea sr eported by Eaton was COT].…”

Section: Scheme3synthesismentioning

confidence: 99%

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

Houston

¹

,

Xing

²

,

Bernhardt

³

et al. 2019

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Perhaps the primary concern regarding the use of cubane in both academic and industrial settings is the availability of suitable cubane precursors on significant scale. This has largely been addressed with our finding that dimethyl cubane‐1,4‐dicarboxylate ( 13 ) can be produced in kilogram quantities . All analogues ( 4 , 6 , 8 , 10 a – 10 c , 12 ) were synthesized from this precursor using standard transformations.…”

Section: Figurementioning

confidence: 99%

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Chalmers

¹

,

Xing

²

,

Houston

³

et al. 2016

Self Cite

View full text Add to dashboard Cite

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.

show abstract

“…[25] Perhaps the primary concern regarding the use of cubane in both academic and industrial settings is the availability of suitable cubane precursors on significant scale.T his has largely been addressed with our finding that dimethyl cubane-1,4-dicarboxylate (13)c an be produced in kilogram quantities. [26] All analogues (4, 6, 8, 10 a-10 c, [27] 12)were synthesized from this precursor using standard transformations.Asecondary concern, however, is functional-group placement and manipulation. When compared to synthetic chemistry associated with the benzene ring, cubane chemistry is not as well established.…”

Section: Angewandte Chemiementioning

confidence: 99%

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Chalmers

¹

,

Xing

²

,

Houston

³

et al. 2016

Self Cite

View full text Add to dashboard Cite

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.

show abstract

Pilot-Scale Production of Dimethyl 1,4-Cubanedicarboxylate

Cited by 53 publications

References 54 publications

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Contact Info

Product

Resources

About