TY - JOUR

T1 - Aromatic oligoamides with a rare ortho-connectivity

T2 - synthesis and study of ortho-arylopeptoids

AU - Hjelmgaard, T.

AU - Nielsen, John

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Even though aromatic oligoamides composed of aromatic amino acids in a "one-way sequence" attract ever increasing research interest, backbones connected through ortho-linked aromatics remain rare. Herein, we present the first synthesis and study of N-alkylated ortho-aminomethyl- benzamides termed "ortho-arylopeptoids". The ortho-arylopeptoids may, with a few exceptions, be synthesized either in solution or on solid-phase using unique and highly efficient submonomer methods with similar levels of high generality and efficiency to those previously demonstrated for meta- and para-arylopeptoids. NMR studies indicated a more restricted rotation about the amide bonds in ortho-arylopeptoids, presumably due to a more congested backbone structure resulting from the ortho-connectivity pattern. Intriguingly, tert-butyl and phenyl side chains offer complete control over the amide conformations; whereas arylopeptoid residues with tert-butyl side chains adopt a 100 % cis amide conformation, the opposite 100 % trans amide conformation was observed in arylopeptoids with phenyl side chains. The tert-butyl moiety can furthermore serve as a protecting group during synthesis, which can later be removed to allow the amide to adopt a 100 % trans conformation instead.

AB - Even though aromatic oligoamides composed of aromatic amino acids in a "one-way sequence" attract ever increasing research interest, backbones connected through ortho-linked aromatics remain rare. Herein, we present the first synthesis and study of N-alkylated ortho-aminomethyl- benzamides termed "ortho-arylopeptoids". The ortho-arylopeptoids may, with a few exceptions, be synthesized either in solution or on solid-phase using unique and highly efficient submonomer methods with similar levels of high generality and efficiency to those previously demonstrated for meta- and para-arylopeptoids. NMR studies indicated a more restricted rotation about the amide bonds in ortho-arylopeptoids, presumably due to a more congested backbone structure resulting from the ortho-connectivity pattern. Intriguingly, tert-butyl and phenyl side chains offer complete control over the amide conformations; whereas arylopeptoid residues with tert-butyl side chains adopt a 100 % cis amide conformation, the opposite 100 % trans amide conformation was observed in arylopeptoids with phenyl side chains. The tert-butyl moiety can furthermore serve as a protecting group during synthesis, which can later be removed to allow the amide to adopt a 100 % trans conformation instead.

UR - http://www.scopus.com/inward/record.url?scp=84878784528&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201300398

DO - 10.1002/ejoc.201300398

M3 - Journal article

AN - SCOPUS:84878784528

VL - 2013

SP - 3574

EP - 3589

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

SN - 1434-193X

IS - 17

ER -