Efficient protocols for the synthesis of enantiopure γ‐amino acids with proteinogenic side chains

Abstract

The synthesis of enantiopure gamma-substituted gamma-amino acids with proteinogenic side chains, starting from the corresponding natural alpha-amino acids, was studied. N-Protected amino aldehydes containing various protective groups were prepared from the corresponding amino alcohols by oxidation with NaOCl in the presence of AcNH-TEMPO and directly reacted with methyl, benzyl and tert-butyl phosphoranylidene acetate to produce alpha,beta-unsaturated gamma-amino esters. Simultaneous hydrogenation of the double bond and removal of either the benzyl or benzyloxycarbonyl group led to N- or C-protected gamma-amino acids in high yield. The enantiomeric purity was studied by 1H NMR analysis of Mosher amides and chiral HPLC analysis.

Samarium diiodide-induced reductive coupling of chiral nitrones with methyl acrylate

“…4,5 The derivatives of γ-amino buryric acid (GABA) could be potential, selective and irreversible inhibitors of GABA amino transferase, the enzyme involved in the catabolism of GABA. 6,7 As in principle γ-lactams should be easily obtained from the corresponding γ-N-hydroxylamino esters we have paid our attention to the synthesis of biologically important γ-amino acids from the sugar-derived nitrones previously used by us in the chiral cycloadditions. In this communication we wish to describe the SmI 2 -induced coupling of N-benzylsubstituted D-xylose and D-lyxose derived nitrones with methyl acrylate under the formation of chiral 4-substituted γ-N-hydroxylamino esters.…”

Stereoselective synthesis of γ-amino acids

“…Finally, catalytic hydrogenation of 307 followed by treatment with trifluoroacetic acid produced N-Fmoc-c-amino acid 309a in 58% yield (Scheme 71). 127 More recently, Tamamura et al 128 reported the synthesis of N-Fmoc-c-amino acid 309b under a similar protocol. Thus, the reduction of amide 310 obtained from L L-b-(2-naphthyl)alanine, with DIBAL-H, followed by HornerWadsworth-Emmons reaction afforded the N-Boc-c-amino acid tert-butyl ester 311 in 78% yield, which by catalytic hydrogenation gave compound 312 in 74% yield.…”

Synthesis of γ‐Aminobutyric Acid Analogs

“…The key step is a Michael addition of the lithium anion of diethyldifluoromethanephosphonate to a p-chloro-b-nitro styrene (112). Reduction of the nitro functionality and ester hydrolysis of (113) affords the desired phosphonic amino acids (114).…”

“…Alternatively, a Wittig reaction with an alkyl (triphenylphosphoranylidene)acetate on a-amino aldehydes such as phenylalaninal (115) and subsequent reduction of the resulting alkene (116) has been employed (Scheme 14.33). Hydrolysis of the protecting group affords the g-substituted g-amino acid (117) [112].…”