226413-52-1

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 122762-89-4 2-phenylcyclopropenone 2,2-dimethyl-1,3-propanediyl acetal 
• 65265-97-6 [13C]-phenylacetone 
• 79069-51-5 (S)-N-tert-butoxycarbonylvalinal 

Relevant academic research and scientific papers

Cyclopropenone-containing cysteine proteinase inhibitors. Synthesis and enzyme inhibitory activities

By focusing on the amphiphilic properties of cyclopropenone (e.g. a good electrophile and a precursor for a stable 2π-aromatic hydroxycyclopropenium cation), a new class of cysteine proteinase inhibitors containing a cyclopropenone moiety was designed. For the purpose of the present research, we needed to devise a new method to introduce a peptide-related moiety as a substituent on the cyclopropenone residue. We investigated the reaction of metalated cyclopropenone acetal derivatives (2, R2=metal) with N-protected α-aminoaldehydes 4 to obtain the adduct 5, and succeeded in the preparation of highly potentiated cysteine proteinase inhibitors 8 after several steps transformations. They showed strong inhibitory activities only to cysteine proteinases such as calpain, papain, cathepsin B, and cathepsin L and not to serine (e.g. thrombin and cathepsin G) and asparatic protainases (e.g. cathepsin D). Kinetic studies indicated that they are competitive inhibitors, and by the examinations of their inhibitory mechanism it became clear that they are reversible inhibitors. Copyright (C) 1999 Elsevier Science Ltd.

Peptidyl cyclopropenones: Reversible inhibitors, irreversible inhibitors, or substrates of cysteine proteases?

Peptidyl cyclopropenones were previously introduced as selective cysteine protease reversible inhibitors. In the present study we synthesized one such peptidyl cyclopropenone and investigated its interaction with papain, a prototype cysteine protease. A set of kinetics, biochemical, HPLC, MS, and 13C-NMR experiments revealed that the peptidyl cyclopropenone was an irreversible inhibitor of the enzyme, alkylating the catalytic cysteine. In parallel, this cyclopropenone also behaved as an alternative substrate of the enzyme, providing a product that was tentatively suggested to be either a spiroepoxy cyclopropanone or a gamma-lactone. Thus, a single family of compounds exhibits an unusual variety of activities, being reversible inhibitors, irreversible inhibitors and alternative substrates towards enzymes of the same family.

CYCLOPROPENE DERIVATIVES

The cyclopropene derivatives of the present invention are useful as the intermediates for producing cyclopropenone derivatives exhibiting strong inhibition activity of thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L and the like.