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Two sulfur-containing amino acids are included in the list of the 20 classical protein amino acids. A methionine residue is introduced at the start of the synthesis of all current proteins. Cysteine, thanks to its thiol function, plays an essential role in a very large number of catalytic sites. Here we present what is known about the prebiotic synthesis of these two amino acids and homocysteine, and we discuss their introduction into primitive peptides and more elaborate proteins. 1 Introduction 2 Sulfur Sources 3 Prebiotic Synthesis of Cysteine 4 Prebiotic Synthesis of Methionine 5 Homocysteine and Its Thiolactone 6 Methionine and Cystine in Proteins 7 Prebiotic Scenarios Using Sulfur Amino Acids 8 Introduction of Cys and Met in the Genetic Code 9 Conclusion [ABSTRACT FROM AUTHOR]

Reactive acyl trifluoromethanesulfonates are formed from the reaction of acyl fluorides with trimethylsilyl trifluoromethanesulfonate (TMSOTf). These electrophiles undergo Friedel-Crafts reactions with electron-rich aromatics at room temperature. When a sulfur atom is present at their γ position, their cyclization to acylsulfonium cations is observed and is followed by a rearrangement leading to benzothiepinones (or dibenzo[b,e]thiepinones) in 40-85% yield. [ABSTRACT FROM AUTHOR]

Since methionine is capable of self-activation, the dipeptides formed by the reaction of its activated form with another amino acid were over-represented in the primitive ocean. This hypothesis gives a key role to methionine in the development of life on the Earth. It could explain why a methionine residue begins the synthesis of all proteins, while it is usually not necessary for its catalytic activity, and why the start codon is relatively variable in prokaryotes. [ABSTRACT FROM PUBLISHER]

The synthesis of four natural bis(indole) alkaloids of topsentin class 1 and 2 is described. Their bis(indole) α-carbonylimidazoline and subsequently bis(indole) α-carbonylimidazole moieties have been built via the condensation between indolic α-ketothioimidate salts 4 and 1-(indol-3′-yl)-1,2-diaminoethane 3. This compound results from the β-amino indolic hydroxylamine 5 by a two-step sequence. This is the first total synthesis of compounds 1d, 2a, and 2b. [ABSTRACT FROM AUTHOR]

Unlike its shorter analog, cysteine, and its methylated derivative, methionine, homocysteine is not today a proteinogenic amino acid. However, this thiol containing amino acid is capable of forming an activated species intramolecularly. Its thiolactone could have made it an interesting molecular building block at the origin of life on Earth. Here we study the cyclization of homocysteine in water and show theoretically and experimentally that in an acidic medium the proportion of thiolactone is significant. This thiolactone easily reacts with amino acids to form dipeptides. We envision that these reactions may help interpret why a methionine residue is introduced at the start of all protein synthesis. [ABSTRACT FROM AUTHOR]

Homocysteine is a non-proteinogenic sulfur-containing amino acid. Like cysteine, it can form disulfide bridges and complex metallic cations. It is also closely related to methionine, the first amino acid in the synthesis of all contemporary proteins. Furthermore, its cyclized form, a five-membered ring thiolactone, is stable in acidic and neutral water. Here, we demonstrate that this thiolactone may have been formed in the primitive ocean directly from the Strecker precursor of homocysteine, an aminonitrile. Even though it is poorly reactive, this thiolactone may be open by some amines, yielding amides which, in turn, could be the precursors of longer peptides. [ABSTRACT FROM AUTHOR]

At the origin of life, extremely diverse mixtures of oligomers and polymers could be obtained from relatively simple molecular bricks. Here, we present an example of the polymerization of two amidonitriles derived from cysteine, Cys-Ala-CN and Cys-Met-CN. The thiol function in a molecule adds onto the nitrile group of another one, allowing efficient condensation reactions and making available an extensive range of polymers containing amide bonds and/or five-membered heterocycles, namely thiazolines. Macrocycles were also identified, the biggest one containing sixteen residues (cyclo(Cys-Met)8). MALDI-TOF mass spectrometry was used to identify all the present species. What these examples show is that complex mixtures are likely to have formed on the primitive Earth and that, ultimately, the selection that must have followed may have been an even more crucial step towards life than the synthesis of the pre-biological species themselves. [ABSTRACT FROM AUTHOR]

The multiplicity of simple molecules available on the primitive Earth probably made possible the development of extremely diverse prebiotic chemistry. The importance of thiols is widely recognized in the community studying the origin of life. De Duve's "thioester world" has been considered a major contribution in this regard, where thioester bonds have high energies and thus can contribute to several chemical reactions. Herein, we propose specific models of thiols that exhibit unique activities toward several chemical reactions. Thanks to aminothiol and aminonitrile behaviors, we were able to obtain thiol-rich peptides with interesting catalytic activities leading to the formation of structurally diverse molecules. In a broader context, such chemistry could be introduced into systems chemistry scenarios in which it would be associated with the chemistry of nucleic acids or their precursors, as well as that of fatty acids. [ABSTRACT FROM AUTHOR]

A concise total synthesis of (+)-hyacinthacine A2, a polyhydroxylated pyrrolizidine alkaloid, is described using our recently discovered inversion of the C-N bond polarity in nitrones. In the key step, the diastereoselective reductive coupling of a L-xylose-derived cyclic nitrone with ethyl acrylate allowed the assembly of the bicyclic core of the target molecule, by way of a tandem formation of the C-C and C-N bonds. The method opens a novel, short, and general route for the synthesis of other pyrrolizidine alkaloids. [ABSTRACT FROM AUTHOR]

Theoretical and experimental work has been conducted about possible prebiotic syntheses of cysteine. Activated derivatives of this amino acid can oligomerize and polymerize to afford various poly‐thiazolines and cysteine‐rich chains. [ABSTRACT FROM AUTHOR]

The feasibility of the cyclization of γ-alkylthiobutyric acid derivatives to form previously unknown five-membered-ring acyl sulfonium cations was studied. Experimental results were in good agreement with our DFT calculations that predicted such cyclizations to be easy if starting with acyl iodides and mixed anhydrides of triflic acid. Particularly efficient were the reactions of γ-alkylthiobutyryl fluorides with trimethylsilyl triflate in CDCl3 solution, which led to cyclic acyl sulfonium triflates. In some cases, the observed acyl sulfonium salts were stable enough to be characterized by NMR spectroscopy. They were found to be both alkyl-transfer reagents and acylating agents. They react with amines to form amides. These findings lend some weight to our hypothesis that the acyl sulfonium derived from methionine may have played a major role in the prebiotic synthesis of the first peptides on the primitive Earth. [ABSTRACT FROM AUTHOR]

Abstract: N-Benzylnitrones react with heteroaromatic compounds such as pyrroles or furan in the presence of hydrogen chloride. Either heteroaromatic N-benzylhydroxylamines, symmetrical or unsymmetrical 2,2′-bis(heteroaryl)alkanes could be selectively produced depending on the experimental conditions. [Copyright &y& Elsevier]

Total syntheses of enantiopure hanishin, longamide B, and longamide B methyl ester are described. Absolute configurations of these natural products have been established. [ABSTRACT FROM AUTHOR]

To develop new 99mTc--label led agents to evaluate dopamine transporters (DAT) involved in Parkinson's disease, by in vivo SPECT imaging, we have synthesized six new sulfur-containing ligands with the tropane skeleton. We have introduced the complexing sulfur atom far from the three sites of recognition by DAT of these tropane derivatives. The 6β-substituted tropinone has been obtained by a double Mannich condensation followed by the introduction of the moieties for molecular interactions at the binding site on C2 and C3, leading to the six stereoisomers. [ABSTRACT FROM AUTHOR]

The preparation and the crystal structure of the title compound are described. The unit-cell dimensions are: a = 8.711(4), b = 12.549(3), c = 20.643(4) A˚, β = 92.21(4)°. Space group is the monoclinic P21/c with Z = 4. The crystal structure determination was run by using 4560 independent reflections with a final R-value of 0.052 (Rw = 0.083). To cite this article: M. David et al., C. R. Chimie 7 (2004). [Copyright &y& Elsevier]

1,3-Asymmetric induction in the Et2Zn-catalyzed addition of terminal alkynes was studied with nitrones bearing a chiral auxiliary on their nitrogen atom. The obtained propargylic N-hydroxylamines were generally isolated in good yields and with satisfactory to excellent diastereoselectivities. [Copyright &y& Elsevier]

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives resulted in significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using the PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient when using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of the Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This equates to an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction. [ABSTRACT FROM AUTHOR]

The centrality of pyruvate oxidative decarboxylation into acetyl-CoA in current biochemistry is a strong argument for proposing that a similar reaction have been necessary for the development of an effective protometabolism on the primitive Earth. However, such a decarboxylation requires the use of an oxidant and a catalyst, today enzymatic. Based on the mechanisms of the pyruvate dehydrogenase complex and pyruvate-ferredoxin oxidoreductase, we propose that the initial mechanism involved disulfides and occurred via radicals. A first disulfide is obtained by reacting glyoxylate with hydrogen sulfide. It is then possible to produce a wide variety of other disulfides by exchange reactions. When reacted with pyruvate under UV light they give thioesters. This process requires no oxidant and is therefore compatible with what is known of the redox conditions of the early Earth. Neither does it require any catalyst. It could be the first way to acetyl thioesters, a way that was later improved by the introduction of catalysts, first minerals, then enzymes. [ABSTRACT FROM AUTHOR]

Abstract: The first total synthesis of enantiopure (S)-(−)-cyclooroidin is described. Absolute configuration of this natural product has been confirmed by comparison of the optical rotation value of our synthetic sample with the one measured on natural cyclooroidin. [Copyright &y& Elsevier]

The Strecker reaction of aldehydes with ammonia and hydrogen cyanide first leads to α-aminonitriles, which are then hydrolyzed to α-amino acids. However, before reacting with water, these aminonitriles can be trapped by aminothiols, such as cysteine or homocysteine, to give 5- or 6-membered ring heterocycles, which in turn are hydrolyzed to dipeptides. We propose that this two-step process enabled the formation of thiol-containing dipeptides in the primitive ocean. These small peptides are able to promote the formation of other peptide bonds and of heterocyclic molecules. Theoretical calculations support our experimental results. They predict that α-aminonitriles should be more reactive than other nitriles, and that imidazoles should be formed from transiently formed amidinonitriles. Overall, this set of reactions delineates a possible early stage of the development of organic chemistry, hence of life, on Earth dominated by nitriles and thiol-rich peptides (TRP). [ABSTRACT FROM AUTHOR]