N-Aminosulfamide Peptide Mimic Synthesis by Alkylation of Aza-sulfurylglycinyl Peptides

Abstract

N-Aminosulfamides are peptidomimetics in which the C(α)H and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of N-protected amino hydrazides and p-nitrophenylsulfamidate esters. The installation of N-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation.

Solid-Phase Synthesis of Azasulfurylphenylalanine4-GHRP-6

“…The required AsF-tripeptide building block was synthesized in solution by a route featuring the construction and alkylation of azasulfurylglycine (AsG) tripeptide 3, which was made without formation of symmetric sulfamide side product by acylation of hydrazide 2 with p-nitrophenyl-sulfamidate 1 (Scheme 1) [3]. Chemoselective alkylation on the AsG-tripeptide 3 using benzyl bromide and tetraethylammonium hydroxide installed the benzyl side-chain onto the N-aminosulfamide residue.…”

“…Azasulfurylpeptides possess an amino sulfamide as an amino amide surrogate in which the CH and carbonyl components are respectively replaced by nitrogen and a sulfonyl group [1][2][3][4]. Uniting the properties of azapeptides [5] and sulfonamides [6][7], azasulfurylpeptides have served as transition state mimics of amide bond hydrolysis in a micromolar human immunodeficiency virus-1 (HIV-1) proteinase inhibitor [2].…”

Synthesis of N-Methyl and Azasulfuryl Urotensin-II(4-11) Derivatives

“…In [AsF 7 ]hU-II(4-11) (8), the Trp 7 residue was replaced by azasulfurylphenylalanine with the phenyl group serving as a mimic of the indole moiety. Initially, the AsF tripeptide building block 5 was synthesized using a solution-phase approach featuring chemoselective alkylation of azasulfurylglycine (AsG) 4 with benzyl bromide and tert-butylimino-tri(pyrrolidino)phosphorane (BTPP) as base [4].…”

“…Employing the minimal active sequence, we have developed synthetic strategies to prepare new derivatives in which N-methylated (1) and azasulfuryl (2) residues have been inserted into the cyclic peptide core region (Figure 1). Mono and multiple N-methylation of the amide bonds and insertion of N-aminosulfamide residues into hU-II (4)(5)(6)(7)(8)(9)(10)(11) have been performed to survey their influences on intra-and inter-molecular hydrogen bonds, geometry and interactions with UT.…”

crystal structure analyses of azasulfuryltripeptides reveal potential for γ‐turn mimicry†

“…Hydrazide acylation with amino acid‐derived 4‐nitrophenyl sulfamidates 9 has provided azasulfuryltripeptides without formation of symmetric sulfamide side product . Furthermore, chemoselective alkylations of azasulfurylglycine (AsG) tripeptides 5a have facilitated the insertion of various side‐chains onto the N –aminosulfamide residue (Scheme ) …”