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Design and synthesis of highly reactive dienophiles for the tetrazine-trans-cyclooctene ligation.

ABSTRACT: Computation was used to design a trans-cyclooctene derivative that displays enhanced reactivity in the tetrazine-trans-cycloctene ligation. The optimized derivative is an (E)-bicyclo[6.1.0]non-4-ene with a cis-ring fusion, in which the eight-membered ring is forced to adopt a highly strained 'half-chair' conformation. Toward 3,6-dipyridyl-s-tetrazine in MeOH at 25 °C, the strained derivative is 19 and 27 times more reactive than the parent trans-cyclooctene and 4E-cyclooct-4-enol, respectively. Toward 3,6-diphenyl-s-tetrazine in MeOH at 25 °C, the strained derivative is 160 times more reactive than the parent trans-cyclooctene.

SUBMITTER: Taylor MT

PROVIDER: S-EPMC3230318 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Design and synthesis of highly reactive dienophiles for the tetrazine-trans-cyclooctene ligation.

Taylor Michael T MT Blackman Melissa L ML Dmitrenko Olga O Fox Joseph M JM

Journal of the American Chemical Society 20110606 25

Computation was used to design a trans-cyclooctene derivative that displays enhanced reactivity in the tetrazine-trans-cycloctene ligation. The optimized derivative is an (E)-bicyclo[6.1.0]non-4-ene with a cis-ring fusion, in which the eight-membered ring is forced to adopt a highly strained 'half-chair' conformation. Toward 3,6-dipyridyl-s-tetrazine in MeOH at 25 °C, the strained derivative is 19 and 27 times more reactive than the parent trans-cyclooctene and 4E-cyclooct-4-enol, respectively. ...[more]

PMID: 21599005

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| S-EPMC3230322 | biostudies-literature

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives.

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