79671-38-8

Upstream product

• 33002-26-5 2-methyl-3-(trimethylsilyl)cycloprop-3-ene-1-carboxylic acid ethyl ester 
• 79671-36-6 (2-methyl-3-(trimethylsilyl)-cycloprop-2-en-1-yl)methanol 

Relevant academic research and scientific papers

Synthesis and reactivity comparisons of 1-methyl-3-substituted cyclopropene mini-tags for tetrazine bioorthogonal reactions

Substituted cyclopropenes have recently attracted attention as stable "mini-tags" that are highly reactive dienophiles with the bioorthogonal tetrazine functional group. Despite this interest, the synthesis of stable cyclopropenes is not trivial and their reactivity patterns are poorly understood. Here, the synthesis and comparison of the reactivity of a series of 1-methyl-3-substituted cyclopropenes with different functional handles is described. The rates at which the various substituted cyclopropenes undergo Diels-Alder cycloadditions with 1,2,4,5-tetrazines were measured. Depending on the substituents, the rates of cycloadditions vary by over two orders of magnitude. The substituents also have a dramatic effect on aqueous stability. An outcome of these studies is the discovery of a novel 3-amidomethyl substituted methylcyclopropene tag that reacts twice as fast as the fastest previously disclosed 1-methyl-3-substituted cyclopropene while retaining excellent aqueous stability. Furthermore, this new cyclopropene is better suited for bioconjugation applications and this is demonstrated through using DNA templated tetrazine ligations. The effect of tetrazine structure on cyclopropene reaction rate was also studied. Surprisingly, 3-amidomethyl substituted methylcyclopropene reacts faster than trans-cyclooctenol with a sterically hindered and extremely stable tert-butyl substituted tetrazine. Density functional theory calculations and the distortion/interaction analysis of activation energies provide insights into the origins of these reactivity differences and a guide to the development of future tetrazine coupling partners. The newly disclosed cyclopropenes have kinetic and stability advantages compared to previously reported dienophiles and will be highly useful for applications in organic synthesis, bioorthogonal reactions, and materials science.

NOVEL TETRAZINES AND METHOD OF SYNTHESIZING THE SAME

Provided herein, inter alia, are compositions and methods of synthesis and detection of tetrazines and diazonorcaradienes.

SYNTHESIS OF 3-VINYLCYCLOPROPENE DERIVATIVES

Derivatives of 3-vinylcyclopropene were synthesized from 1,2-dimethyl-3-acetyl-, 1,2-dimethyl-3-formyl-, and 1-methyl-2-trimethylsilyl-3-formylcyclopropenes and the corresponding triphenylalkylidenephosphoranes.