Asymmetric Synthesis of α‐Amino Acids from Glycine

Abstract

Enantioselective synthesis of optically active α‐amino acids from glycine via Schiff base employing (+)‐N,N‐diisopropyl‐10‐camphorsulfonamide as a chiral template is described.

Enantioselective Synthesis of (R)-3-(3,4-Dihydroxyphenyl)alanine from tert-Butyl Glycinate

“…(1 S )-1,1-Dimethylethyl 2-( N , N -Bis(1-methylethyl)-7,7-dimethyl-1-methanesulfonamidobicyclo[2.2.1]hept-2-ylidene amino)ethanoate (2). 4a, A mixture of tert -butyl glycinate (157 mg, 1.20 mmol) and thione 3 (331 mg, 1.00 mmol) in toluene (7 mL) was heated under reflux for 24 h. After cooling, the mixture was filtered. The filtrate was concentrated and purified by silica gel column chromatography eluted with ethyl acetate−hexane (1:5) to give Schiff base 2 (417 mg, 98%): mp 68.0−69.5 °C (hexane); [α] 23 D 23.5 ( c 2.00, CHCl 3 ); IR (KBr) 1735, 1684 cm -1 ; 1 H NMR δ 3.94, 3.92 (ABq, J = 16.0 Hz, 2H), 3.77 (septet, J = 6.8 Hz, 2H), 3.70 (d, J = 14.4 Hz, 1H), 2.86 (d, J = 14.4 Hz, 1H), 2.61 (ddd, J = 12.2, 12.0, 4.4 Hz, 1H), 2.27 (ddd, J = 16.8, 3.6, 3.6 Hz, 1H), 1.97−1.87 (m, 2H), 1.79 (d, J = 16.8 Hz, 1H), 1.56−1.54 (m, 1H), 1.43 (s, 9H), 1.31 (d, J = 6.8 Hz, 6H), 1.30 (d, J = 6.8 Hz, 6H), 1.30−1.20 (m, 1H), 1.16 (s, 3H), 0.83 (s, 3H); 13 C NMR δ 183.3, 169.2, 80.7, 55.1, 54.7, 52.8, 48.0, 47.7, 43.8, 34.9, 27.9, 27.2, 27.0, 22.5, 21.9, 20.0, 19.4; HRMS calcd for C 22 H 41 O 4 N 2 S (M + 1), 429.2788, found 429.2796.…”

“…Since the discovery of l -3-(3,4-dihydroxyphenyl)alanine ( l -DOPA) for the treatment of Parkinson's disease, the preparation of this specific compound has attracted considerable synthetic attention . The synthesis of optically active α-amino acids has been intensively investigated in the past couple decades. , We have reported that enantioselective synthesis of α-amino acids from the asymmetric enolate alkylation of Schiff base, derived from the condensation of tert -butyl glycinate with N-substituted or N,N-disubstituted (1 S )-(+)-10-camphorsulfonamides, could be achieved in high ee . Here, we report an enantioselective synthesis of d -DOPA with high ee employing this method.…”

“…Direct condensation of (1 S )-(+)- N , N -diisopropyl-10-camphorsulfonamide 1 with excess tert -butyl glycinate in refluxing toluene for 48 h could give Schiff base 2 in 71% yield 4a. Alternatively, Schiff base 2 could be prepared in a more practical sense and avoid the use of excess tert -butyl glycinate and purification problems.…”

“…Without HMPA, the reaction was slow and resulted in low yield of product. On the basis of our previous experience, the newly formed stereogenic center was assigned as R . Hydrolysis of Schiff base 4 could be achieved by treatment with hydroxyamine in HOAc−NaOAc to give the corresponding aminoester 5 in high yield.…”

Hippophae salicifolia D. Don: A Miraculous Species Less Known in Europe

“…Some studies have suggested that this species is a potential source of bioactive antimicrobial agents and could be used as a natural preservative and for nutraceutical formulations (Gupta et al, 2011a). The leaves and seeds has a higher total phenolic content, comparing to other sea buckthorn species (Lu, 1992), as well leaves showed antiinflammatory properties (Padwad et al, 2006). During the last year, extracts from this plant were used in the USA as an food supplement (Saikia and Handique, 2012).…”