Trans-cycloheptenes and hetero-trans-cycloheptenes for bioorthogonal coupling

Patent metadata

Field	Value
Publication number	US-10155777-B2
Application number	US-201615564540-A
Country	US
Kind code	B2
Filing date	Apr 7, 2016
Priority date	Apr 8, 2015
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

A substituted trans-cycloheptene according to formula (I); wherein: a) Z and L are each selected from the group consisting of SiR 1 R 2 , CH 2 , CHOH, and CHR 2 ; R 1 is phenyl or CH 3 ; R 2 is phenyl, CH 3 , (CH 2 ) n CN, or (CH 2 ) n OH, wherein n is an integer from 1 to 5; R a and R b are each individually selected from the group consisting of H, OH, and CH 3 ; and Z and L are not both SiR 1 R 2 ; or b) Z is BocN, L is CH 2 , R a is H, and R b is H; or c) Z is C=0, L is CH 2 , R a is H, and R b is H.

First claim

What is claimed is:

1. A substituted trans-cycloheptene according to formula (I)

wherein:
a) Z and L are each selected from the group consisting of SiR 1 R 2 , CH 2 , CHOH, and CHR 2 ; R 1 is phenyl or CH 3 ; R 2 is phenyl, CH 3 , (CH 2 ) n CN, or (CH 2 ) n OH, wherein n is an integer from 1 to 5; R a and R b are each individually selected from the group consisting of H, OH, and CH 3 ; and Z and L are not both SiR 1 R 2 ; or
b) Z is BocN, L is CH 2 , R a is H, and R b is H; or
c) Z is C═O, L is CH 2 , R a is H, and R b is H.

2. The substituted trans-cycloheptene according to claim 1 , wherein Z, L, R a , and R b are according to any one of combinations a) through l):
a) Z is CHOH, L is CH 2 , R a is H, and R b is H;
b) Z is CH 2 CHOH, L is CH 2 , R a is H, and R b is H;
c) Z is CH 2 , L is CH 2 , and R a is OH, and R b is H;
d) Z is CH 2 , L is CHOH, R a is OH, and R b is H;
e) Z is BocN, L is CH 2 , R a is H, and R b is H;
f) Z is C═O, L is CH 2 , R a is H, and R b is H;
g) Z is SiR 1 R 2 , L is CH 2 , R a is H, R b is H, R 1 is CH 3 , and R 2 is either (CH 2 ) 3 CN or (CH 2 ) 4 OH;
h) Z is SiCH 3 (CH 2 ) 3 OH, L is CH 2 , R a is CH 3 , and R b is CH 3 ;
i) Z is SiPh 2 , L is CH 2 , R a is H, and R b is H;
j) Z is Si(CH 3 ) 2 , L is CH 2 , R a is OH, and R b is H;
k) Z is CH 2 , L is SiPh 2 , R a is H, and R b is H;
l) Z is CH 2 , L is SiCH 3 (CH 2 ) 4 OH, R a is H, R b is H.

3. A method of performing a bioorthogonal coupling reaction, comprising contacting a tetrazine, ketene, conjugated diene, or 1,3-dipole, in each case substituted with a biomolecule, with a trans-cycloheptene or a hetero-trans-cycloheptene according to claim 1 .

Assignees

• Fox Joseph
• Zhang Han
• Fang Yinzhi
• Univ Delaware

Inventors

• Fox Joseph
• Zhang Han
• Fang Yinzhi

Classifications

• C07C13/24

  with a seven-membered ring · CPC title

• C07C49/547

  to a seven- to twelve-membered ring · CPC title

• C07F7/0807 Primary

  comprising Si as a ring atom · CPC title

• C07D237/30

  Phthalazines · CPC title

• G01N33/58

  involving labelled substances (G01N33/53 takes precedence) · CPC title