501331-02-8Relevant articles and documents
Synthesis and biological evaluation of gramicidin S-inspired cyclic mixed α/β-peptides
Van Der Knaap, Matthijs,Basalan, Fatih,Van De Mei, Henny C.,Busscher, Henk J.,Van Der Marel, Gijsbert A.,Overkleeft, Herman S.,Overhand, Mark
, p. 2494 - 2506 (2013/01/16)
Via a Mannich reaction involving a dibenzyliminium species and the titanium enolates of Evans' chiral acylated oxazolidinones the β2-amino acids (R)- and (S)-Fmoc-β2homovaline and (R)-Fmoc- β2homoleucine are synthesized. T
Enantioselective synthesis of beta-amino acids using hexahydrobenzoxazolidinones as chiral auxiliaries
Reyes-Rangel, Gloria,Jimenez-Gonzalez, Erika,Olivares-Romero, Jose Luis,Juaristi, Eusebio
experimental part, p. 2839 - 2849 (2009/06/18)
A practical synthetic route for the asymmetric synthesis of β2-amino acids is described. In the first step, the procedure involves the N-acylation of readily available, enantiopure hexahydrobenzoxazolidinone (4R,5R)-1 with 3-methylbutanoyl chloride 2, 4-methylpentanoic acid 3, and 3-(1-tert-butoxycarbonyl)-1H-indol-3-yl)propanoic acid 4 to afford derivatives 5a, 5b, and 5c, respectively, which were alkylated with high diastereoselectivity by means of reaction between their sodium enolates and benzyl bromoacetate. Removal of the chiral auxiliary from the alkylated products followed by hydrogenation and hydrolysis gave β2-amino acids (S)-10a, (S)-10b, and (S)-10c, which were N-protected with Fmoc. Enantiomeric (R)-10a-c were similarly prepared from the isomeric hexahydrobenzoxazolidinone (4S,5S)-1; thus, the route presented here provides access to both enantiomers of valuable highly enantioenriched β2-amino acids.
Preparation of N-Fmoc-Protected β2- and β3-Amino Acids and Their Use as Building Blocks for the Solid-Phase Synthesis of β-Peptides
Guichard, Gilles,Abele, Stefan,Seebach, Dieter
, p. 187 - 206 (2007/10/03)
N-Fmoc-Protected (Fmoc = (9H-fluoren-9-ylmethoxy)carbonyl) β-amino acids are required for an efficient synthesis of β-oligopeptides on solid support. Enantiomerically pure Fmoc-β3-amino acids (β3: side chain and NH2 at C(3)(=C(β))) were prepared from Fmoc-protected (S)- and (R)-α-amino acids with aliphatic, aromatic, and functionalized side chains, using the standard or an optimized Arndt-Eistert reaction sequence. Fmoc-β2-Amino acids (β2 side chain at C(2), NH2 at C(3)(=C(β))) configuration bearing the side chain of Ala, Val, Leu, and Phe were synthesized via the Evans' chiral auxiliary methodology. The target β3-heptapeptides 5-8, a β3- pentadecapeptide 9 and a β2-heptapeptide 10 were synthesized on a manual solid-phase synthesis apparatus using conventional solid-phase peptide synthesis procedures (Scheme 3). In the case of β3-peptides, two methods were used to anchor the first β-amino acid: esterification of the ortho-chlorotrityl chloride resin with the first Fmoc-β-amino acid 2 (Method I, Scheme 2) or acylation of the 4-(benzyloxy)benzyl alcohol resin (Wang resin) with the ketene intermediates from the Wolff rearrangement of amino-acid-derived diazo ketone 1 (Method II, Scheme 2). The former technique provided better results, as exemplified by the synthesis of the heptapeptides 5 and 6 (Table 2). The intermediate from the Wolff rearrangement of diazo ketones 1 was also used for sequential peptide-bond formation on solid support (synthesis of the tetrapeptides 11 and 12). The CD spectra of the β2- and β3-peptides 5, 9. and 10 show the typical pattern previously assigned to an (M) 31 helical secondary structure (Fig.). The most intense CD absorption was observed with the pentadecapeptide 9 (strong broad negative Cotton effect at ca. 213 nm); compared to the analogous heptapeptide 5, this corresponds to a 2.5 fold increase in the molar ellipticity per residue!
