University of Delaware

Massachusetts Institute of Technology

University of Southern California

Joseph M Fox

Yixin Xie

Yinzhi Fang

Colin Thorpe

Melissa Blackman

Han Zhang

Stephen L Buchwald

Peter Conti

Christopher William Am Ende

Zibo Li

Xinqiao Jia

Peter S Conti

Joel Rosenthal

Ni Yan

Amanda M Tallon

William Trout

Will Trout

Shuang Liu

Ashlyn S Cantrel

Julia E Rosenberger

Matthew Hassink

William Lambert

Chuanqi Wang

Subham Mahapatra

Ramajeyam Selvaraj

Maksim Royzen

Disclosed herein are mono- and di-substituted tetrazines and methods of their preparation and converting an oxetanyl ester to a thio-substituted tetrazine, which is then converted to a mono-substituted tetrazine, a di-substituted tetrazine, or a vinylether disubstituted tetrazine.

Reagents and methods for tetrazine synthesis

A method for catalytically converting a dihydrotetrazine 1 into a tetrazine 2, wherein the dihydrotetrazine 1 comprises a first R group and a second R group, wherein the first R group is a substituted or unsubstituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, carbonyl, or heteroatom-containing group, and the second R group is selected from the group consisting of H and substituted or unsubstituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, carbonyl, and heteroatom-containing groups; wherein the method comprises (a) providing the dihydrotetrazine 1 in a reaction medium, and (b) adding an enzyme as a catalyst and an oxidant to the reaction medium, whereby the dihydrotetrazine 1 is converted to the tetrazine 2.

Methods for inducing bioorthogonal reactivity

A method for catalytically converting a dihydrotetrazine 1 into a tetrazine 2, wherein one R group on the dihydrotetrazine 1 is a substituted or unsubstituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, carbonyl, or heteroatom-containing group, and the other R group is selected from the group consisting of H and substituted or unsubstituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, carbonyl,- or heteroatom-containing groups; 1, 2 wherein the method comprises oxidizing dihydrotetrazine 1 in a reaction medium in the presence of a catalyst and a stoichiometric oxidant. 

A Diels-Alder adduct of a trans-cyclooctene with a tetrazine is provided, wherein the adduct bears a substituent labeled with a radionuclide. A method of producing a PET or other image of an organ in an animal or human includes forming the Diels-Alder adduct in the animal or human. Trans-cyclooctenes and tetrazines suitable for preparing the adducts are provided.

Tetrazine-trans-cyclooctene ligation for the rapid construction of radionuclide labeled probes

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

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

Coupling reactions, suitable for use in organic or aqueous media, are performed by contacting a 1,2,4,5-tetrazine with a dienophile. The dienophile may be covalently bonded to a protein, and the coupling reaction may be performed in biological media such as those containing cells or cell lysates. The reactions may be performed in the presence of primary amines, thiols, acetylenes, azides, phosphines, and products of Staudinger and/or Sharpless-Huisgen reactions Novel 3-substituted cyclopropene compounds and trans-cyclooctenes are exemplary dienophiles for these reactions.

Tetrazine-based bio-orthogonal coupling reagents and methods

The present invention relates to a process for the preparation of N-aryl amine and N-aryl amide compounds. Generally, the process of the present invention involves reacting a compound having a primary or secondary amino or amido group with an arylating compound, in the presence of a weak base and a transition metal catalyst, under reaction conditions effective to form an N-aryl amine or N-aryl amide compound, the transition metal catalyst comprising a Group 8 metal, e.g., Ni, Pd, or Pt, and at least one carbene-containing ligand. Typically, the transition metal catalyst is formed in a preceding step from the conjugate acid form of the carbene ligand, a stoichiometric amount of a strong base, and a Group 8 metal atom or ion.

Transition-metal-catalyzed carbon-nitrogen bond-forming methods using carbene ligands

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Landenberg, PA, United States of America

Joseph M Fox