Preparation of Pseudo‐Peptide Building Blocks with retro‐Thioamide Bond Mediated via Thiocarbamoyl Meldrum's Acid

Abstract

An easy and efficient synthesis of pseudo‐tripeptide containing a thiomalonamide moiety was developed. Isothiocyanate derivatives of amino acids react smoothly with 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione (Meldrum's acid) to yield new thiocarbamoyl derivatives of Meldrum's acids. Thermal decomposition of these new derivatives leads to thiocarbamoyl ketenes, which acylate amino acid esters to give pseudo‐tripeptides.

Thermal Decomposition of Carbamoyl Meldrum's Acids: A Starting Point for the Preparation of 1,3‐Oxazine Derivatives

“…Recently, we have focused on the synthetic application of carbamoyl Meldrum's acid thus developing protocols for forming 3‐carbamoyl‐β‐lactams or pseudopeptides . In our most in‐depth research, we focused on possibly forming 3‐carbamoyl‐β‐lactams; however, some combinations of reagents eluded the usual rules, leading to unexpected products.…”