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Synthesis and NMR Analysis in Solution of Oligo(3‐hydroxyalkanoic acid) Derivatives with the Side Chains of Alanine, Valine, and Leucine ( β ‐Depsides): Coming Full Circle from PHB to β ‐Peptides to PHB
Author(s) -
Albert Matthias,
Seebach Dieter,
Duchardt Elke,
Schwalbe Harald
Publication year - 2002
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(200202)85:2<633::aid-hlca633>3.0.co;2-1
Subject(s) - chemistry , stereochemistry , alanine , side chain , monomer , peptide , nuclear magnetic resonance spectroscopy , tripeptide , amino acid , organic chemistry , biochemistry , polymer
Oligomers of 3‐hydroxyalkanoic acids that contain two, three, and six residues with and without O‐terminal ( t Bu)Ph 2 Si and C‐terminal PhCH 2 protection have been synthesized in such a way that the side chains on the oligoester backbone were those of the proteinogenic amino acids Ala (Me), Val (CHMe 2 ), and Leu (CH 2 CHMe 2 ). The enantiomerically pure 3‐hydroxyalkanoates were obtained by Noyori hydrogenation of the corresponding 3‐oxo‐alkanoates with [Ru(( R )‐binap)Cl 2 ](binap=2,2′bis(diphenylphosphanyl)‐1,1′‐binaphthalene)/H 2 ( Scheme 1 ), and the coupling was achieved under the conditions (pyridine/(COCl) 2 , CH 2 Cl 2 , −78°) previously employed for the synthesis of various oligo(3‐hydroxybutanoic acids) ( Schemes 2 and 3 ). The Cotton effects in the CD spectra of the new oligoesters provided no hints about chiral conformation ( cf. a helix) in MeOH, MeCN, octan‐1‐ol, or CF 3 CH 2 OH solutions ( Figs. 1 and 2 ). Detailed NMR investigations in CDCl 3 solution ( Figs. 3 – 6 , and Tables 1 – 5 ) of the hexa(3‐hydroxyalkanoic acid) with the side chains of Val (HC), Ala (HB), Leu (HH), Val, Ala, Leu (from O‐ to C‐terminus; 3 ) gave, on the NMR time‐scale, no evidence for the presence of any significant amount of a 2 1 ‐ or a 3 1 ‐helical conformation, comparable to those identified in stretched fibers of poly[( R )‐3‐hydroxybutanoic acid], or in lamellar crystallites and in single crystals of linear and cyclic oligo[( R )‐3‐hydroxybutanoic acids], or in the corresponding β ‐peptide(s) (the oligo(3‐aminoalkanoic acid) analogs; 1 – 3 ). Thus, the extremely high flexibility (averaged or ‘random‐coil' conformation) of the polyester chain (CO−O rotational barrier ca. 13 kcal/mol; no hydrogen bonding), as compared to polyamide chains (CO−NH barrier ca. 18 kcal/mol; hydrogen bonding) has been demonstrated once again. The possible importance of this structural flexibility, which goes along with amphiphilic properties, for the role of PHB in biology, in evolution, and in prebiotic chemistry is discussed. Structural similarities of natural potassium‐channeling proteins and complexes of oligo(3‐hydroxybutanoates) with Na + , K + , or Ba 2+ are alluded to ( Figs. 7 – 9 ).