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Preparation of ( S , S )‐Fmoc‐ β 2 hIle‐OH, ( S )‐Fmoc‐ β 2 hMet‐OH, and ( S )‐Fmoc‐ β 2 hTyr( t Bu)‐OH for Solid‐Phase Syntheses of β 2 ‐ and β 2 / β 3 ‐Peptides
Author(s) -
Sebesta Radovan,
Seebach Dieter
Publication year - 2003
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.200390337
Subject(s) - chemistry , isopropyl , amino acid , solid phase synthesis , stereochemistry , organic chemistry , peptide , biochemistry
The preparation of three new N ‐Fmoc‐protected (Fmoc=[(9 H ‐fluoren‐9‐yl)methoxy]carbonyl) β 2 ‐homoamino acids with proteinogenic side chains (from Ile, Tyr, and Met) is described, the key step being a diastereoselective amidomethylation of the corresponding Ti‐enolates of 3‐acyl‐4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐ones with CbzNHCH 2 OMe/TiCl 4 (Cbz=(benzyloxy)carbonyl) in yields of 60–70% and with diastereoselectivities of >90%. Removal of the chiral auxiliary with LiOH or NaOH gives the N ‐Cbz‐protected β ‐amino acids, which were subjected to an N ‐Cbz/ N ‐Fmoc (Fmoc=[(9 H ‐fluoren‐9‐yl)methoxy]carbonyl) protective‐group exchange. The method is suitable for large‐scale preparation of Fmoc‐ β 2 hXaa‐OH for solid‐phase syntheses of β ‐peptides. The Fmoc‐amino acids and all compounds leading to them have been fully characterized by melting points, optical rotations, IR, 1 H‐ and 13 C‐NMR, and mass spectra, as well as by elemental analyses.