Auguste Commeyras

N-Carbamoyl-α-Amino Acids Rather than Free α-Amino Acids Formation in the Primitive Hydrosphere: A Novel Proposal for the Emergence of Prebiotic Peptides

Our previous kinetic and thermodynamic studies upon the reactional system HCHO/HCN/ NH3 in aqueous solutions are completed. In the assumed prebiotic conditions of the primitive earth ([HCHO] and [HCN] near 1 g L−1, T = 25 °C, pH = 8, [NH3] very low), this system leads to 99.9% of α-hydroxyacetonitrile and 0.1% of α-aminoacetonitrile (precursor of the α-amino acid). The classical base-catalyzed hydration of nitriles, slow and not selective, can not modify significantly this proportion. On the contrary, we found two specific and efficient reactions of α-aminonitriles which shift the initial equilibrium in favor of the α-aminonitrile pathway. The first reaction catalyzed by formaldehyde generates α-aminoamides, precursors of α-aminoacids. The second reaction catalyzed by carbon dioxide affords hydantoins, precursors of N-carbamoyl-α-aminoacids. In the primitive hydrosphere, where the concentration in carbon dioxide was estimated to be higher than that of formaldehyde, the formation of hydantoins was consequently more efficient. The rates of hydrolysis of the α-aminoacetamide and of the hydantoin at pH 8 being very similar, the synthesis of the N-carbamoyl-α-amino acid seems then to be the fatal issue of the HCHO/HCN/NH3 system that nature used to perform its evolution. These N-protected α-amino acids offer new perspectives in prebiotic chemistry, in particular for the emergence of peptides on the prebiotic earth.

Synthesis of terminally perfluorinated long-chain alkanethiols, sulfides and disulfides from the corresponding halides

Abstract Semifluorinated n -alkanethiols, symmetrical sulfides and disulfides bearing the chain(s) F(CF 2 ) n (CH 2 ) m with n =4, 6, 8, 10, and m =2, 11 have been prepared by various synthetic methods, starting from the corresponding iodides or bromides. Methods based on sodium hydrogen sulfide, commonly used to accomplish this conversion, treatment of the Bunte salt obtained from sodium thiosulfate, the basic hydrolysis of isothiouronium salts, the hydrolysis under mild conditions of thiophosphorates formed from sodium thiophosphate and the basic hydrolysis of thiol acetic acid derivatives, have been investigated and compared relatively to the selective synthesis of the title compounds. The thiolacetic route yields essentially the thiols with some amounts of disulfides. Results from thiourea appears similar. Sodium thiophosphate constitutes an excellent route for the synthesis of thioethers, particularly when starting from the bromides. The two classical methods based on sodium hydrogen sulfide and sodium thiosulfate exhibit poor selectivity. It has been possible to obtain all the sulfur compounds reported in the pure state.

A new simple and quantitative synthesis of α-aminoacid-N-carboxyanhydrides (oxazolidines-2,5-dione)

Abstract Nitrosation of chiral N-carbamoylaminoacids with a mixture of NO and O 2 gives, with the same configuration and in quantitative yield the corresponding α-aminoacid-N-carboxyanhydrides (NCA), well known precursors of peptides. The by products of this reaction are N 2 and H 2 O.

An Expeditious Multigram-Scale Synthesis of Lysine Dendrigraft (DGL) Polymers by Aqueous N-Carboxyanhydride Polycondensation

The synthesis and characterisation of new arborescent architectures of poly(L-lysine), called lysine dendrigraft (DGL) polymers, are described. DGL polymers were prepared through a multiple-generation scheme (up to generation 5) in a weakly acidic aqueous medium by polycondensing N(epsilon)-trifluoroacetyl-L-lysine-N-carboxyanhydride (Lys(Tfa)-NCA) onto the previous generation G(n-1) of DGL, which was used as a macroinitiator. The first generation employed spontaneous NCA polycondensation in water without a macroinitiator; this afforded low-molecular-weight, linear poly(L-lysine) G1 with a polymerisation degree of 8 and a polydispersity index of 1.2. The spontaneous precipitation of the growing N(epsilon)-Tfa-protected polymer (GnP) ensures moderate control of the molecular weight (with unimodal distribution) and easy work-up. The subsequent alkaline removal of Tfa protecting groups afforded generation Gn of DGL as a free form (with 35-60% overall yield from NCA precursor, depending on the DGL generation) that was either used directly in the synthesis of the next generation (G(n+1)) or collected for other uses. Unprotected forms of DGL G1-G5 were characterised by size-exclusion chromatography, capillary electrophoresis and (1)H NMR spectroscopy. The latter technique allowed us to assess the branching density of DGL, the degree of which (ca. 25%) turned out to be intermediate between previously described dendritic graft poly(L-lysines) and lysine dendrimers. An optimised monomer (NCA) versus macroinitiator (DGL G(n-1)) ratio allowed us to obtain unimodal molecular weight distributions with polydispersity indexes ranging from 1.3 to 1.5. Together with the possibility of reaching high molecular weights (with a polymerisation degree of ca. 1000 for G5) within a few synthetic steps, this synthetic route to DGL provides an easy, cost-efficient, multigram-scale access to dendritic polylysines with various potential applications in biology and in other domains.

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.

Dendrigraft Poly-L-lysine: A Non-Immunogenic Synthetic Carrier for Antibody Production

An easily synthesized DendriGraft poly-lysine DGL-G3 (third generation) was shown to act as an efficient carrier for raising antibodies directed against small molecules. The immunological properties of three different forms of DGL-G3 were investigated: the native form (molecular weight 22 kDa bearing a mean number of 123 surface amino groups as TFA salts), a form modified at the C-terminus by fluorescein (fluorescein-DGL-G3), and last a surface-modified form bearing histamine (DGL-G3-Histamine). Our studies demonstrate the native DGL-G3 to be inefficient in eliciting antibody production in rabbits. Immunizations of rabbits using the core-modified fluorescein-DGL-G3 or the surface-modified DGL-G3-histamine conjugate failed in eliciting antibody production. Conversely, following a primary immunization using a BSA-histamine conjugate, a second immunization with DGL-G3-histamine conjugate improved the production of specific hapten-directed antibodies, which demonstrates the utility of DGL-G3 as a carrier for the production of highly specific antibody against haptens.

Reactivite comparee des perfluoroiodoalcanes (RFI) et des perfluoroalcoyl-2 iodo-1 ethanes (RFC2H4I) en presence de couple metallique zinc-cuivre dans les solvants phosphates d'alcoyles

Abstract Reactivity of perfluoroalkyl iodides R F I and 1-perfluoroalkyl-2-iodoethanes R F C 2 H 4 I, in presence of a zinc-copper couple in alkyl phosphates solvents, is described. R F I and R F C 2 H 4 I react via an organometalllc route to give per- and poly-fluoroorganozinc (R F ZnI and R F C 2 H 4 ZnI) compounds. Then, in particular conditions, they react with alkyl to give phosphoro-fluorinated molecules (phosphinates, phosphine oxides, phosphines). The compoundss stabilities are studied.

Synthesis of perfluoroalkyl carboxylic acids by reaction of perfluoroalkyl iodides with electrogenerated superoxide ion

Abstract The electrogenerated superoxide ion Of]2°- is shown to react with perfluoroalkyliodides to afford F-alkyl carboxylic acids. A mechanism is proposed on the basis of the results obtained in preparative experiments and by cyclic voltammetry.

Thermolyse des halogenures de perfluoroalcanesulfonyle

Abstract Perfluoroalkanesulfonyl chlorides [R F SO 2 Cl ; R F  CF 3 , C 2 F 3 , C 4 F 9 ], decompose thermally to give the corresponding perfluoroalkyl chlorides with evolution of SO 2 . The latter retards the reaction, but it is catalysed by copper which also inhibits the SO 2 effect. 2-methyl-2-nitrosopropane traps the perfluoroalkyl free radicals. In the presence of a perfluoroalkyl iodide [R′ F I ≠ R′ F ≠R F ], other products, R F I and R F Cl, are obtained. A free radical chain-mechanism is then suggested. On the other hand, perfluorobutanesulfonyl fluoride is very stable thermally.

Electrolytic reductive coupling. addition of perfluoroalkyliodides to alcenes

Abstract Addition of perfluoroalkyliodides (R F I) to alcenes has been and is extensively studied using radical initiators and UV light irradiation. In this work, the addition of R F I (R F = CF 3 (CF 2 ) n n = 4,6,8) to allylic and propargylic alcohol, and to diallyl ether is performed using and electrochemical initiation. Electrolysis is realised in two kinds of cell: 1. mercury cathode, DMF, LiClO 4 electrolyte. 2. fiber carbon cathode, water Kcl electrolyte. We obtain addition compounds and/or products resulting from the electrochemical increase of pH in the catholyte. When using an aqueous electrolyte, the organic phase is dispersed in water. This heterogeneous electrolysis appears as a very quick, high yield route, expected compounds being obtained in a pure phase. The mechanism observed when working with allylic alcohol is : The formation of the iodhydrine appears as resulting from a radical catalytic process initiated by the electrochemical reduction of R F I. When the organic phase (R F I + CH 2 = CH-CH 2 OH) is completely converted to iodhydrine, the electrolysis of the water phase produces an increase of pH in the catholyte. Consequently, the iodhydrine is converted to the epoxide: Similar reactions have been performed: