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Synthesis of Tri‐, Penta‐, and Heptapeptides Containing and ( R )‐2‐alkyl‐2‐amino‐3‐(methylamino)‐propionic acid residue in the central position
Author(s) -
Seebach Dieter,
Studer Armido,
Pfammatter Elmar,
Widmer Hans
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770728
Subject(s) - chemistry , tetrapeptide , peptide , moiety , residue (chemistry) , stereochemistry , epimer , amino acid , saponification , side chain , racemization , alkyl , organic chemistry , biochemistry , polymer
By conventional peptide‐coupling methods (C to N direction; mixed anhydride, bis(2)‐oxooxazolidin‐3‐yl)phosphinoyl chloride (Bop‐Cl), or dicyclohexylcarbodiimide (DCC), 2‐amino‐2‐methyl‐3‐(methylamino)‐propionic acid and 2‐amino‐2‐ethyl‐3‐(methylamino)propionic acid ( = 2‐amino‐2‐[(methylamino)methyl]butanoic acid) are incorporated in the central position of tri‐, penta‐, and heptapeptides (see 3 – 7 , 21 , and 22 ). The fragment coupling of the β ‐amino group of the diamino‐acid moiety in a tetrapeptide led to partial epimerization, and thus, two epimeric heptapeptide derivatives were actually obtained ( 7 and epi‐ 7 ). The final deprotection to the free heptapeptide (involving a Me 3 SiI cleavage of BocNH and MeOCONH, a saponification with NaOH, and HPLC purification) gave both the desired product (isopeptide 21 ), with the β ‐amino group inside the peptide backbone, and a product (peptide 22 ) of transpeptidation, with the α‐amino group of the diamino acid incorporated and a (methylamino)methyl group as the side chain. Peptide 22 is completely converted to the isopeptide 21 by prolonged treatment with base. The heptapeptide 21 was analyzed by elaborate 2QF‐COSY and NOESY NMR measurements in H 2 O/CD 3 OD at −5° ( Table , Fig. ); there is no indication for β ‐sheet or helical structures, a fact which was also confirmed by CD measurements.