Anwendung der Azirin/Oxazolon‐Methode in der Peptid‐Chemie: Synthese von Modell‐Tripeptiden

Abstract

The Azirine/Oxazolone Method in Peptide Chemistry: Synthesis of Tripeptide ModelsTripeptides 5, containing an'a,a -disubstituted a-amino acid and ethyl p-aminobenzoate, were synthesized in high yield by application of the azirine/oxazolone method ( Table 2). In this versatile approach for the incorporation of disubstituted residues into the peptide chain, N-protected peptides or amino acids are coupled with 2,2-dialkyl-3-amino-2H-azirines and, after the selective hydrolysis of the newly formed C-terminal amid bond, further condensed with amino components via in situ generated oxazole-5(4H)-ones in the presence of additives (Scheme I ) . A comparison with conventional procedures clearly demonstrates the advantages of this new method that works equally well with P-branched, cyclic, or acyclic disubstituted amino acids.

Conformational Characterization of the 1-Aminocyclobutane-1-carboxylic Acid Residue in Model Peptides

“…Interestingly, linear di-and tripeptides containing the Ac 4 c residue were previously synthesized by Heimgartner and coworkers [24][25][26] using a 2Hazirine as the Ac 4 c equivalent.…”

ChemInform Abstract: Heterospirocyclic N‐(2H‐Azirin‐3‐yl)‐L‐prolinates: New Dipeptide Synthons.

“…Selective hydrolysis of the C-terminal amide group [19] of the molecular structure of 7 (with 50% probability ellipsoids) under the conditions described by Wipf [21] (3n HCl in THF/H 2 O 1 : 1, room temperature) gave, after 1 h, the acid 13 in 81% yield, contaminated with 10 ± 15% of the starting material 12. Deprotection of the NH 2 group by catalytic hydrogenation yielded 11, which was coupled to Z-Ser( t Bu)-OH with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) in MeCN to yield 82% of Z-Ser( t Bu)-Val-Thp-Pro-Aib-N(Me)Ph (12) as a pale yellow oil.…”

HeterospirocyclicN-(2H-Azirin-3-yl)-L-prolinates: New Dipeptide Synthons

“…Deprotection of the NH 2 group by catalytic hydrogenation yielded 11, which was coupled to Z-Ser( t Bu)-OH with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) in MeCN to yield 82% of Z-Ser( t Bu)-Val-Thp-Pro-Aib-N(Me)Ph (12) as a pale yellow oil. Selective hydrolysis of the C-terminal amide group [19] of the molecular structure of 7 (with 50% probability ellipsoids) under the conditions described by Wipf [21] (3n HCl in THF/H 2 O 1 : 1, room temperature) gave, after 1 h, the acid 13 in 81% yield, contaminated with 10 ± 15% of the starting material 12.…”