General, Mild, and Metal-Free Synthesis of Phenyl Selenoesters from Anhydrides and Their Use in Peptide Synthesis

A mild, practical, and simple procedure for phenyl selenoesters synthesis from several anhydrides and diphenyl diselenide was developed. This transition-metal-free method provides a straightforward entry to storable Fmoc-amino acid selenoesters which are effective chemoselective acylating reagents. An application to oligopeptide synthesis was illustrated

A One-Pot Procedure for the Preparation of <i>N</i>‑9-Fluorenylmethyloxycarbonyl-α-amino Diazoketones from α‑Amino Acids

The study describes a new “one-pot” route to the synthesis of <i>N</i>-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting <i>N</i>-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of <i>N</i>-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that <i>tert</i>-butyloxycarbonyl (Boc), <i>tert</i>-butyl (^<i>t</i>Bu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding <i>C</i>-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective <i>N</i>-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of <i>N</i>-Fmoc-protected dipeptidyl diazoketones

Chemoselective Protection of Glutathione in the Preparation of Bioconjugates: The Case of Trypanothione Disulfide

A novel synthetic route to the chemoselectively protected <i>N</i>,<i>S-</i>ditritylglutathione monomethyl ester is described involving the chemical modification of the commercially available glutathione (GSH). The synthetic value of this building block in the facile preparation of GSH bioconjugates in a satisfying overall yield was exemplified by the case of trypanothione disulfide (TS₂), a GSH-spermidine bioconjugate, involved in the antioxidative stress protection system of parasitic protozoa, such as trypanosoma and leishmania parasites

Synthesis of d-<i>erythro</i>-Sphinganine through Serine-Derived α‑Amino Epoxides

A total synthesis of d-<i>erythro</i>-sphinganine [(2<i>S</i>,3<i>R</i>)-2-amino­octa­decane-1,3-diol] starting from commercial <i>N</i>-<i>tert</i>-butyl­oxy­carbonyl-l-serine methyl ester is described. The approach is based on the completely stereo­selective preparation of an α-amino epoxide obtained by treating a protected l-serinal derivative with dimethyl­sulfoxo­nium methylide. The oxirane synthon is obtained with an <i>anti</i> configuration fitting the (2<i>S</i>,3<i>R</i>) stereochemistry of the 2-amino-1,3-diol polar head of d-<i>erythro</i>-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting l-serine material