637337-64-5

Upstream product

• 637337-58-7 (4R)-3-[(2S)-2-({[(benzyloxy)carbonyl]amino}methyl)-4-bromo-1-oxobutyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one 
• 5188-07-8 sodium thiomethoxide 
• 32391-97-2 4-(methylthio)butanoic acid 
• 637337-42-9 (4R)-3-(4-bromo-1-oxobutyl)-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one 
• 191090-32-1 (R)-4-(1-methylethyl)-5,5-diphenyl-1,3-oxazolidin-2-one 
• 94471-35-9 benzyl N-(methoxymethyl) carbamate 
• 637337-48-5 (R)-4-isopropyl-3-(4-methylsulfanyl-1-oxobutyl)-5,5-diphenyloxazolidin-2-one 

Downstream Products

• 637337-73-6 (S)-2-({[(benzyloxy)carbonyl]amino}methyl)-4-(methylsulfanyl)butanoic acid 

Relevant academic research and scientific papers

Preparation of β2-amino acid derivatives (β2hThr, β2hTrp, β2hMet, β2hPro, β2hLys, pyrrolidine-3-carboxylic acid) by using DIOZ as chiral auxiliary

The title compounds were prepared from valine-derived N-acylated oxazolidin-2-ones, 1-3, 7, 9, by highly diastereoselective (≥ 90%) Mannich reaction (→ 4-6; Scheme 1) or aldol addition (→ 8 and 10; Scheme 2) of the corresponding Ti- or B-enolates as the key step. The superiority of the '5,5-diphenyl-4-isopropyl-1,3-oxazolidin-2-one' (DIOZ) was demonstrated, once more, in these reactions and in subsequent transformations leading to various t-Bu-, Boc-, Fmoc-, and Cbz-protected β2-homoamino acid derivatives 11-23 (Schemes 3-6). The use of ω-bromo-acyl-oxazolidinones 1-3 as starting materials turned out to open access to a variety of enantiomerically pure trifunctional and cyclic carboxylic-acid derivatives.

Preparation of (S,S)-Fmoc-β2hIle-OH, (S)-Fmoc-β 2hMet-OH, and (S)-Fmoc-β2hTyr(tBu)-OH for Solid-Phase Syntheses of β2- and β2/β 3-Peptides

The preparation of three new N-Fmoc-protected (Fmoc=[(9H-fluoren-9-yl)methoxy]carbonyl) β2-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 CbzNHCH2OMe/TiCl4 (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=[(9H-fluoren-9-yl)methoxy]carbonyl) protective-group exchange. The method is suitable for large-scale preparation of Fmoc-β2hXaa-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, 1H- and 13C-NMR, and mass spectra, as well as by elemental analyses.