ABSTRACT
Protein total chemical synthesis enables the atom-by-atom control of the protein structure and therefore has a great potential for studying protein function. Native chemical ligation of C-terminal peptide thioesters with N-terminal cysteinyl peptides and related methodologies are central to the field of protein total synthesis. Consequently, methods enabling the facile synthesis of peptide thioesters using Fmoc-SPPS are of great value. Herein, we provide a detailed protocol for the preparation of bis(2-sulfanylethyl)amino polystyrene resin as a starting point for the synthesis of C-terminal bis(2-sulfanylethyl)amido peptides and of peptide thioesters derived from 3-mercaptopropionic acid.
Subject(s)
Esters/chemical synthesis , Peptides/chemical synthesis , Polystyrenes/chemical synthesis , Resins, Synthetic/chemical synthesis , Chemistry Techniques, Synthetic , Peptides/chemistry , Polystyrenes/chemistry , Resins, Synthetic/chemistry , Sulfonamides/chemistryABSTRACT
Reaction of bis(2-sulfanylethyl)amido (SEA) peptides with triisopropylsilylthiol in water at neutral pH yields peptide thiocarboxylates. An alkylthioester derived from ß-alanine was used to trap the released bis(2-sulfanylethyl)amine and displace the equilibrium toward the peptide thiocarboxylate.
Subject(s)
Amides/chemistry , Carboxylic Acids/chemical synthesis , Peptides/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Carboxylic Acids/chemistry , Hydrogen-Ion Concentration , Molecular Structure , Peptides/chemistry , Sulfhydryl Compounds/chemistryABSTRACT
5-Substituted 6,7-dihydrodibenz[c,e]azepines, a class of secondary amine incorporating a centre-axis chirality relay, are accessible from 1-substituted N-(2-bromobenzyl)-1-phenylmethanamines via N-acylation and ring-closing intramolecular direct arylation. The ring closure proceeds with high atropodiastereoselectivity due to strain effects that are induced by trigonalisation of the nitrogen atom, as predicted using molecular mechanics calculations.
ABSTRACT
(-)-5-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine 4, a new secondary amine featuring an axis-center stereochemical relay, was prepared enantioselectively from 2'-acetylbiphenyl-2-carboxylic acid, using (R)-2-phenylglycinol as an auxiliary for the control of both elements of chirality. The biaryl axis in 4 preferentially adopts the aS-configuration, with the methyl substituent pseudoequatorial, but conversion into the corresponding N-Boc derivative locks the axis into the aR-configuration, as predicted on the basis of molecular mechanics calculations.
