Divergent Behavior of Glycosylated Threonine and Serine Derivatives in Solid Phase Peptide Synthesis

Abstract

Solid phase peptide coupling of glycosylated threonine derivatives was systematically evaluated. In contrast to glycosylated serine derivatives which are highly prone to epimerization, glycosylated threonine derivatives produce only negligible amounts of epimerization. Under forcing conditions, glycosylated threonine analogs undergo β-elimination, rather than epimerization. Mechanistic studies and molecular modeling were used to understand the origin of the differences in reactivity.

Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles

“…We employed coupling conditions that were determined previously by our laboratory to minimize racemization of the α-carbon of the amino acid. 85,86 Final stages for the preparation of the desired AuNP ligand included Fmoc deprotection with piperidine, acetylation of the resulting amino group with acetic anhydride in methanol and Zemplèn deprotection of all O- and S-protected acetates resulting in thiols 10a and 10b . For the preparation of the control ligand, compound 2 was processed directly to the thioacetate 11 and hydrolyzed to 12 ; this compound was used directly for AuNP synthesis.…”

Facile Synthesis of Optically Active and Magnetic Nanoparticles Carrying Helical Poly(phenyl isocyanide) Arms and Their Application in Enantioselective Crystallization

“…To verify this hypothesis, the nanoparticles were used as specific chiral selector toward enantioselective crystallization. Herein, racemic d / l ‐threonine was taken as a model compound because of their biological important and widely used in organic synthesis . Since the optical activity of poly‐ l ‐ 1 100 ‐Fe 3 O 4 is higher than that of Fe 3 O 4 ‐poly‐ l ‐ 1 100 , the enantioselective crystallization was conducted by adding a predetermined amount of poly‐ l ‐ 1 100 ‐Fe 3 O 4 into a supersaturated aqueous solution of racemic d / l ‐threonine.…”

Copper(I)‐Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β‐Tetrapeptide Analogues

“…According to previous reports, epimerization occurred during solid‐phase peptide synthesis and could produce as much as 80 % of the unnatural epimer for glycosylated serine‐containing peptides . In contrast, less than 1 % epimerization was observed for glycosylated threonine derivatives . The occurrence of epimerization was considered during the coupling processes by activation and cyclization, then abstraction of the α‐hydrogen to form the other epimer (Scheme S1 in the Supporting Information).…”