Asymmetric Synthesis of [2,3-¹³C₂,¹⁵N]-4-Benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one via Lipase TL-Mediated Kinetic Resolution of Benzoin:  General Procedure for the Synthesis of [2,3-¹³C₂,¹⁵N]-l-Alanine

Abstract

Lipase TL-mediated kinetic resolution of benzoin proceeded to give the corresponding optically pure (R)-benzoin (R)-1. On the other hand, (S)-benzoin O-acetate (S)-7 could be hydrolyzed without epimerization to give (S)-benzoin (S)-1 under alkaline conditions. Furthermore, both enantiomers of benzoin (1) were converted to [(15)N]-(1R,2S)- and (1S,2R)- 2-amino-1,2-diphenylethanol (3a and 3b), respectively, according to the procedure reported previously. [2,3-(13)C(2),(15)N]-(5S,6R)-4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one (10) was synthesized from ethyl [1,2-(13)C(2)]bromoacetate and (1R,2S)-2-amino-1,2-diphenylethanol (3b) in three steps. Finally, [2,3-(13)C(2),(15)N]-L-alanine (12) was prepared via alkylation of the lactone 10 and hydrogenation of the alkylated product 11.

Lipase from Pseudomonas stutzeri: Purification, homology modelling and rational explanation of the substrate binding mode

“…Nevertheless, in the kinetic resolution of racemic secondary alcohols, this enzyme is recognizes only a limited range of substrates; in fact, only those carrying one small and one significantly larger substituent at the hydroxymethane centre are transformed with high enantioselectivity [80][81][82][83][84]. Ligands bearing a substituent larger than an ethyl group cannot be recognized, which makes CALB inactive on benzoins [12,13].…”

“…co.jp/meito/kaseihin/index e.html) has proven to be an attractive alternative for the recognition of alcohols possessing large groups at the asymmetric carbon atom, such as wood sterols [10], benzoins [11][12][13] and other bulky secondary alcohols [14][15][16]. On the other hand, this enzyme has been shown to be very active in hydrophobic solvents, such as toluene [15], or polar ones, such as acetone, 1,4-dioxane [16] or THF [11][12][13][14], also displaying an increase in activity and stability upon immobilization [17]. Furthermore, Lipase TL has proven to be also useful for N-acetylalanine deprotection [18], stereoselective acylation of 2-chloro-1-(2,4-difluorophenyl)ethanol [19] or aminolysis reactions [20] in 2-methyltetrahydrofuran (2-MeTHF), a greener substitute for THF displaying very interesting properties.…”

Cysteinyl Peptide Capture for Shotgun Proteomics: Global Assessment of Chemoselective Fractionation

“…The sensitivity of the thiol-IBB conjugate to hydrolysis in mild base is consistent with the properties of similar benzoin esters. (37)…”

Synthesis of Isotopically Labeled α‐Amino Acids

“…Using oxazines, in particular the Williams oxazines supersedes some of these issues as the oxazine ring is cleaved under hydrogenation conditions and the isotopically labeled amino acid is isolated by ion-exchange chromatography. Oxazines have been used extensively for the synthesis of labeled amino acids including aspartic acid, glutamic acid, phenylalanine, tyrosine, lysine, glycine as well as alanine [71][72][73][74][75][76][77]. For example, Williams and coworkers prepared (5S,6R)-½2; 3-13 C 2 ; 15 N4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one 484j 11 Synthesis of Isotopically Labeled a-Amino Acids 59 from benzoin 58 using a lipase-mediated kinetic resolution as the key step (Scheme 11.16) [77].…”