Trans-cyclooctene

and Its Application

Reporter: Peng Yan

Supervisor: Ping Lu

Fudan University

2019-11-1

Background01

The Reaction of TCO—

IEDDA, Click, Bioorthogonal reaction02

03

CONTENTS

Some new reactions of TCO

04 Summary

BackgroundPart 1

M. T. Taylor, M. L. Blackman, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc., 2011, 133, 9646.

The Reaction of TCO02

1

M. T. Taylor, M. L. Blackman, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc., 2011, 133, 9646.

The Reaction of TCO02

2

Optically Active TCO01

W. G. R. Funke, F. N. Jones, A. C. Cope, J. Am. Chem. Soc., 1966, 88, 4693 3

The Reaction of TCO02

F. Thalhammer, U. Wallfahrer, J. Sauer, Tetrahedron Lett., 1990, 31, 6851. 4

Background01

K. Ziegler, H.Wilms, Ann., 1950, 1, 567.; S. W. Fenton, C. F. Spencer, A. C. Cope, J. Am. Chem. Soc., 1952, 74, 5884.

R. A. Pike, C. F. Spencer, A. C. Cope, J. Am. Chem. Soc., 1953, 75, 3212. 5

New Synthesis Method01

J. Deyrup, M. Betkouski, J. Org. Chem., 1972, 37, 3561.

J. S. Swenton, J. Org. Chem., 1969, 34, 3217. 6

New Synthesis Method01

M. Royzen, G. P. A. Yap, J. M. Fox, J. Am. Chem. Soc., 2008, 130, 3760 7

New Synthesis Method01

M. Royzen, G. P. A. Yap, J. M. Fox, J. Am. Chem. Soc., 2008, 130, 3760 8

New Synthesis Method01

M. Royzen, G. P. A. Yap, J. M. Fox, J. Am. Chem. Soc., 2008, 130, 3760

Transannular Cyclization Reaction

9

New Synthesis Method01

A. Darko, S. J. Boydb, J. M. Fox, Synthesis, 2018, 50, 4875. 10

The Reaction of TCOPart 2

N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc., 2004, 126, 15046.

The Reaction of TCO02

Bioorthogonal chemistry: Any chemical reaction that can occur inside

of living systems without interfering with native biochemical processes.

11

N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc., 2004, 126, 15046.

The Reaction of TCO02

By Bertozzi

12

N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc., 2004, 126, 15046.

The Reaction of TCO02

– 2 3 3, [Cu]

k2 of SPAAC = 5 M-1s-1

SPAAC = Strain-Promoted Azide-Alkyne Cycloaddition

13

M. L. Blackman, M. Royzen, J. M. Fox, J. Am. Chem. Soc., 2008, 130, 13518.

Diels-Alder Reactions of Tetrazines with trans-Cyclooctene

Fast Reactivity at Low Micromolar Concentrations

The Reaction of TCO02

14

M. L. Blackman, M. Royzen, J. M. Fox, J. Am. Chem. Soc., 2008, 130, 13518.

The Reaction of TCO02

15

M. T. Taylor, M. L. Blackman, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc., 2011, 133, 9646.

The Reaction of TCO02

ΔGǂ = 8.92 kcal/mol

ΔGǂ = 6.95 kcal/mol

ΔGǂ =8.24 kcal/mol

16

M. T. Taylor, M. L. Blackman, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc., 2011, 133, 9646.

The Reaction of TCO02

17

M. T. Taylor, M. L. Blackman, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc., 2011, 133, 9646.

The Reaction of TCO02

18

A. Darko, S. Wallace, O. Dmitrenko, M. M. Machovina, R. A. Mehl, J. W. Chinb, J. M. Fox, Chem. Sci., 2014, 5, 3770

The Reaction of TCO02

ΔGǂ = 16.09 kcal/mol

ΔGǂ = 13.27 kcal/mol

19

A. Darko, S. Wallace, O. Dmitrenko, M. M. Machovina, R. A. Mehl, J. W. Chinb, J. M. Fox, Chem. Sci., 2014, 5, 3770

The Reaction of TCO02

20

A. Darko, S. Wallace, O. Dmitrenko, M. M. Machovina, R. A. Mehl, J. W. Chinb, J. M. Fox, Chem. Sci., 2014, 5, 3770

The Reaction of TCO02

21

A. Darko, S. Wallace, O. Dmitrenko, M. M. Machovina, R. A. Mehl, J. W. Chinb, J. M. Fox, Chem. Sci., 2014, 5, 3770

The Reaction of TCO02

22

T. Yokoi, T. Ueda, H. Tanimoto, T. Morimoto, K. Kakiuchi, Chem. Commun., 2019, 55, 1891

The Reaction of TCO02

23

T. Yokoi, T. Ueda, H. Tanimoto, T. Morimoto, K. Kakiuchi, Chem. Commun., 2019, 55, 1891 24

Some New Reactions of TCO

Part 3

M. Royzen, M. T. Taylor, A. DeAngelis, J. M. Fox, Chem. Sci., 2011, 2, 2162 – 2165.

Some New Reactions of TCO03

25

M. Royzen, M. T. Taylor, A. DeAngelis, J. M. Fox, Chem. Sci., 2011, 2, 2162 – 2165.

Some New Reactions of TCO03

26

M. Royzen, M. T. Taylor, A. DeAngelis, J. M. Fox, Chem. Sci., 2011, 2, 2162 – 2165.

Some New Reactions of TCO03

27

M. Royzen, M. T. Taylor, A. DeAngelis, J. M. Fox, Chem. Sci., 2011, 2, 2162 – 2165.

Some New Reactions of TCO03

28

M. Royzen, M. T. Taylor, A. DeAngelis, J. M. Fox, Chem. Sci., 2011, 2, 2162 – 2165.

Some New Reactions of TCO03

28

S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara, Angew. Chem. Int. Ed., 2018, 57, 13863 –13867

Some New Reactions of TCO03

29

S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara, Angew. Chem. Int. Ed., 2018, 57, 13863 –13867

Some New Reactions of TCO03

30

S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara, Angew. Chem. Int. Ed., 2018, 57, 13863 –13867 31

S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara, Angew. Chem. Int. Ed., 2018, 57, 13863 –13867

Some New Reactions of TCO03

32

S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara, Angew. Chem. Int. Ed., 2018, 57, 13863 –13867

Some New Reactions of TCO03

33

N. Arichi, K. Yamada, Y. Yamaoka, K. Takasu, J. Am. Chem. Soc., 2015, 137, 9579.

Some New Reactions of TCO03

34

Some New Reactions of TCO03

N. Arichi, K. Yamada, Y. Yamaoka, K. Takasu, J. Am. Chem. Soc., 2015, 137, 9579. 35

Some New Reactions of TCO03

N. Arichi, K. Yamada, Y. Yamaoka, K. Takasu, J. Am. Chem. Soc., 2015, 137, 9579. 36

Some New Reactions of TCO03

N. Arichi, K. Yamada, Y. Yamaoka, K. Takasu, J. Am. Chem. Soc., 2015, 137, 9579. 37

N. Arichi, K. Yamada, Y. Yamaoka, K. Takasu, J. Am. Chem. Soc., 2015, 137, 9579. 38

C. Denk,D. Svatunek, J. Stanek, T. Filip, D. Matscheko, C. Kuntner, T. Wanek, H. Mikula, Bioconjugate Chem. 2016, 27, 1707

PET: Positron emission tomography

39

Some New Reactions of TCO03

C. Denk,D. Svatunek, J. Stanek, T. Filip, D. Matscheko, C. Kuntner, T. Wanek, H. Mikula, Bioconjugate Chem. 2016, 27, 170740

C. Denk,D. Svatunek, J. Stanek, T. Filip, D. Matscheko, C. Kuntner, T. Wanek, H. Mikula, Bioconjugate Chem. 2016, 27, 170741

Some New Reactions of TCO03

b = brain, bl = bladder, k = kidney, lu = lung

C. Denk,D. Svatunek, J. Stanek, T. Filip, D. Matscheko, C. Kuntner, T. Wanek, H. Mikula, Bioconjugate Chem. 2016, 27, 170742

Some New Reactions of TCO03

PET Image

Summary

Part 4

Summary04

43

• Planar chirality

• High HOMO energy

• High energy of ring strain

Properties:

Reaction:

• IEDDA reaction

• Click reaction

• Bioorthogonal reaction

• Total synthesis

• The catalyst of transition metal

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