Stereospecific synthesis of syn-alpha-oximinoamides by a three-component reaction of isocyanides, syn-chlorooximes, and carboxylic acids

A stereospecific multicomponent reaction among isocyanides, nitrile N-oxides and carboxylic acids provides an efficient synthesis of biologically relevant syn \u3b1-oximinoimides

First-in-Class Dual Hybrid Carbonic Anhydrase Inhibitors and Transient Receptor Potential Vanilloid 1 Agonists Revert Oxaliplatin-Induced Neuropathy

Here, we report for the first time a series of compounds potentially useful for the management of oxaliplatin-induced neuropathy (OINP) able to modulate the human Carbonic Anhydrases (hCAs) as well as the Transient Receptor Potential Vanilloid 1 (TRPV1). All compounds showed effective in vitro inhibition activity toward the main hCAs involved in such a pathology, whereas selected items reported moderate agonism of TRPV1. X-ray crystallographic experiments assessed the binding modes of the two enantiomers (R)-37a and (S)-37b within the hCA II cleft. Although the tails assumed diverse orientations, no appreciable effects were observed for their hCA II affinity. Similarly, the activity of (R)-39a and (S)-39b on TRPV1 was not influenced by the stereocenters. In vivo evaluation of the most promising derivatives (R)-12a, (R)-37a, and the two enantiomers (R)-39a, (S)-39b revealed antihypersensitivity effects in a mouse model of OINP with potent and persistent effect up to 75 min after administration

One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3+2] cycloaddition

By combining three appropriately designed simple substrates, a programmed sequence involving an alpha -isocyano acetamide-based three-component reaction followed by a copper-catalyzed intramol. [3+2] cycloaddn. of alkyne and azide took place to afford complex macrocycles, e.g., I, in moderate to good yields. One macrocycle and two heterocycles were produced with concurrent formation of five chem. bonds in this operationally simple process. [on SciFinder (R)