Synthesis of thiourea-tethered C-glycosyl amino acids via isothiocyanate-amine coupling.
A new class of C-glycosyl amino acids displaying a thiourea segment as a linker has been designed and synthesized by addition of peracetylated glycosylmethyl isothiocyanates to an amine-functionalized amino acid (N(alpha)-Fmoc-beta-amino-l-alanine). Three pairs of compounds with alpha- and beta-galacto, alpha- and beta-gluco, and alpha- and beta-manno configuration have been prepared with yields ranging between 70 and 75%. The orthogonal set of protective groups (O-acetyl in the carbohydrate moiety and N-Fmoc in the amino acid residue) makes these compounds suitable substrates for the co-translational modification of natural peptides. The couplings of model hydroxy-free and perbenzylated glycosylmethyl isothiocyanates with the above N(alpha)-Fmoc-beta-amino-l-alanine and the N(alpha)-Boc-protected analogue have been carried out as well, thus broadening the scope of the coupling reaction. Nevertheless, there are limitations of this isothiocyanate-amine coupling in complex systems, and these are briefly discussed.
Barghash
Reham F
RF
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L. Borsari 46, I-44100, Ferrara, Italy.
Massi
Alessandro
A
Dondoni
Alessandro
A
D000409:Alanine / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D017879:Isothiocyanates / Q000737:chemistry; D046188:Protein Modification, Translational; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry
D000588:Amines; D000596:Amino Acids; D002241:Carbohydrates; D017879:Isothiocyanates; C037152:isothiocyanic acid; D013890:Thiourea; D000409:Alanine