193887-45-5

Usage

Uses

Used in Biochemistry Research:
(S)-Fmoc-beta2-homoleucine is used as a research compound for studying the properties and interactions of amino acids and their derivatives. Its unique structure and the presence of the Fmoc protecting group make it a valuable tool in understanding peptide synthesis and related biochemical processes.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (S)-Fmoc-beta2-homoleucine is employed as a building block for the synthesis of novel peptides and peptide-based drugs. Its specific stereochemistry and the ability to incorporate it into peptide chains with controlled side reactions contribute to the development of potential therapeutic agents.
Used in Peptide Synthesis:
(S)-Fmoc-beta2-homoleucine is used as an amino acid component in the synthesis of peptides. The Fmoc protecting group allows for the stepwise construction of peptide chains, with the protection and deprotection of the amino group facilitating the controlled addition of each amino acid. This method is crucial for the synthesis of complex peptide structures with specific biological activities.
Used in Drug Development:
(S)-Fmoc-beta2-homoleucine may be utilized in the development of new drugs, particularly in the design of peptide-based therapeutics. Its unique properties and the ability to incorporate it into peptide sequences can lead to the creation of novel drug candidates with potential applications in various therapeutic areas.

Upstream product

• 1119-16-0 isocaproic aldehyde 
• 941292-88-2 (S)-β-2-methylpropyl-γ-(S)-N-benzyl-α-methylbenzylamino-propylalcohol 
• 501330-95-6 (4S)-isobutyl-2-((S)-1-phenylethyl)-isoxazolidin-5-one 
• 501330-86-5 2-acetyl-4-methyl-pentanoic acid benzyl ester 
• 118053-31-9 benzyl 4-methyl-2-methylenepentanoate 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 203854-56-2 (2S)-([amino]methyl)-4-methylpentanoic acid 

Relevant academic research and scientific papers

Enantioselective H-atom transfer reactions: A new methodology for the synthesis of β2-amino acids

A radical step: The addition of radicals to amino acrylates and subsequent H-atom transfer in the presence of chiral Lewis acid activators provides β2-amino acids in high yields and enantiomeric purity (see scheme; Ln* = chiral ligands, Fmoc = 9-fluorenylmethoxycarbonyl).

Differential Effects of β3- versus β2-Amino Acid Residues on the Helicity and Recognition Properties of Bim BH3-Derived α/β-Peptides

Oligomers containing α- and β-amino acid residues (α/β-peptides) have been shown to mimic the α-helical conformation of conventional peptides when the unnatural residues are derived from β3-amino acids or cyclic β-amino acids, but the impact of incorporating β2 residues has received little attention. The effects of β2 residues on the conformation and recognition behavior of α/β-peptides that mimic an isolated α-helix were investigated. This effort has focused on 26-mers based on the Bim BH3 domain; a set of isomers with identical α/β backbones that differ only in the placement of certain side chains along the backbone (β3 vs. β2 substitution) was compared. Circular dichroism data suggest that β2 residues can be helix-destabilizing relative to β3 residues, although the size of this effect seems to depend on side chain identity. Binding data show that β3→β2 substitution at sites that contact a partner protein, Bcl-xL, can influence affinity in a way that transcends effects on helicity.

Enantioselective synthesis of beta-amino acids using hexahydrobenzoxazolidinones as chiral auxiliaries

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.

Efficient synthesis of enantiomerically pure β2-amino acids via chiral isoxazolidinones

We report a practical and scalable synthetic route for the preparation of α-substituted β-amino acids (β2-amino acids). Michael addition of a chiral hydroxylamine, derived from α-methylbenzylamine, to an α-alkylacrylate followed by cyclization gives a diastereomeric mixture of α-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-β2-amino acids, which are useful for β-peptide synthesis. This route provides access to both enantiomers of a protected β2-amino acid.

Preparation of N-Fmoc-Protected β2- and β3-Amino Acids and Their Use as Building Blocks for the Solid-Phase Synthesis of β-Peptides

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!