Olivier Lagrille

DYNAMIC CO-EVOLUTION OF PEPTIDES AND CHEMICAL ENERGETICS, A GATEWAY TO THE EMERGENCE OF HOMOCHIRALITY AND THE CATALYTIC ACTIVITY OF PEPTIDES

We propose a scenario for the dynamic co-evolution of peptides and energy on the primitive Earth. From a multi component system consisting of hydrogen cyanide, several carbonyl compounds, ammonia, alkyl amine, carbonic anhydride, borate and isocyanic acid, we show that the reversibility of this system leads to several intermediate nitriles, that irreversibly evolve to α-amino acids and N-carbamoyl amino acids via selective catalytic processes. On the primitive Earth these N-carbamoyl amino acids combined with energetic molecules (NOx) may have been the core of a molecular engine producing peptides permanently and assuring their recycling and evolution. We present this molecular engine, a production example, and its various selectivities. The perspectives for such a dynamic approach to the emergence of peptides are evoked in the conclusion.

N‐Carbamoyl Derivatives and Their Nitrosation by Gaseous NOx − A New, Promising Tool in Stepwise Peptide Synthesis

New uses of the N-carbamoyl group in peptide synthesis − as an Nα-protecting group in classical peptide coupling methods, and as a preactivating group for stepwise coupling by NCA formation − are presented. In the first application, the N-carbamoyldipeptide esters C-Val-Gly-OEt, C-Leu-Gly-OEt, C-Ala-Gly-OEt, and C-Ala-Phe-OEt were obtained in good yields by treatment of the corresponding N-carbamoylamino acids (CAA) with amino acid esters. Quantitative N-deprotection without racemisation was then achieved in the solid through nitrosation by gaseous NOx. The extent of racemisation occurring in the coupling step is discussed. In the second application, an easy route to amino acid N-carboxy anhydrides (NCAs) through nitrosation of CAA under the same conditions as above allowed straightforward “one-pot” peptide stepwise coupling, as demonstrated by the formation of Leu-Gly and Val-Gly in good yields and enantiomeric excess. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)