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Synthesis of β ‐Hexa‐ and β ‐Heptapeptides Containing Novel β 2,3 ‐Amino Acids with Two Serine or Two Cysteine Side Chains – CD‐ and NMR‐Spectroscopic Evidence for 3 14 ‐Helical Secondary Structures in Water
Author(s) -
Seebach Dieter,
Jacobi Albrecht,
Rueping Magnus,
Gademann Karl,
Ernst Martin,
Jaun Bernhard
Publication year - 2000
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 - 10.1002/1522-2675(20000906)83:9<2115::aid-hlca2115>3.0.co;2-e
Subject(s) - chemistry , hexa , stereocenter , cysteine , stereochemistry , amino acid , serine , side chain , peptide , aqueous solution , derivative (finance) , cyclohexane , solubility , proton nmr , crystallography , organic chemistry , biochemistry , enzyme , polymer , enantioselective synthesis , catalysis , financial economics , economics
Two representatives of a new type of β ‐amino acids, carrying two functionalized side chains, one in the 2‐ and one in the 3‐position, have been prepared stereoselectively: a β ‐Ser derivative with an additional CH 2 OH group in the 2‐position (for β ‐peptides with better water solubility; Scheme 2 ) and a β ‐HCys derivative with an additional CH 2 SBn group in the 2‐position (for disulfide formation and metal complexation with the derived β ‐peptides; Scheme 3 ). Also, a simple method for the preparation of α ‐methylidene‐ β ‐amino acids is presented (see Boc‐2‐methylidene‐ β ‐HLeu‐OH, 8 in Scheme 3 ). The two amino acids with two serine or two cysteine side chains are incorporated into a β ‐hexa‐ and two β ‐heptapeptides ( 18 and 23/24 , resp.), which carry up to four CH 2 OH groups. Disulfide formation with the β ‐peptides carrying two CH 2 SH groups generates very stable 1,2‐dithiane rings in the centre of the β ‐heptapeptides, and a cyclohexane analog was also prepared ( cf. 27 in Scheme 6 ). The CD spectra in H 2 O clearly indicate the presence of 3 14 ‐helical structures of those β ‐peptides ( 18 , 23 , 24 , 27b ) having the ` right ' configurations at all stereogenic centers ( Fig. 2 ). NMR Measurements ( Tables 1 and 2 , and Fig. 4 ) in aqueous solution of one of the new β ‐peptides ( 24 ) are interpreted on the assumption that the predominant secondary structure is the 3 14 ‐helix, a conformation that has been found to be typical for β ‐peptides in MeOH or pyridine solution, according to our previous NMR investigations.