6336-38-5Relevant articles and documents
Candida antarctica Lipase B in a chemoenzymatic route to cyclic α-quaternary α-amino acid enantiomers
Li, Xiang-Guo,Rantapaju, Maria,Kanerva, Liisa T.
, p. 1755 - 1762 (2011/05/06)
Kinetic resolution of three cyclic quaternary ethyl 1-amino-2,3-dihydro-1H- indene-1-carboxylates and both 1- and 2-amino-1,2,3,4-tetrahydronaphthalene analogues have been studied. Interesterification with butyl butanoate and Candida antarctica lipase B accomplished the task. The enantiomers of all 1-amino analogues reacted with excellent enantioselectivity (enantiomeric ratio er greater than 200), whereas the 2-amino analogue was not enantioselective (er = 4). Amino acid enantiomers were finally obtained as their respective hydrochlorides with almost maximum theoretical yields. For the first time, a lipase enzyme was effectively used in the kinetic resolution of cyclic α-quaternary α-amino esters. Copyright
Enantioselective synthesis of benzocyclic α,α-dialkyl-amino acids: New insight into the solvent dependent stereoselectivity of the TMSCN addition to phenylglycinol derived imines
Warmuth, Ralf,Munsch, Tamara E,Stalker, Robert A,Li, Bing,Beatty, Alicia
, p. 6383 - 6397 (2007/10/03)
Different benzocycloalkane-1-amino-1-carboxylic acids 1a-e have been synthesized via an asymmetric Strecker reaction using (S)-α-methylbenzylamine and (R)-phenylglycinol as chiral auxiliaries. The Zn2+-catalyzed addition of HCN to (S)-α-methylbenzylamine derived ketimines of 1-tetralone (8a) and 1-benzosuberone (8b) yielded mixtures of diastereomeric aminonitriles (1S,1′S)-10a/(1R,1′S)-10a (10:1 ratio) and (1R,1′S)-10b/(1S,1′S)-10b (56:44 ratio), respectively. These aminonitriles are converted to amino acids 1a,b in two steps. The addition of TMSCN to the (R)-phenylglycinol derived ketimines of 8a, 8b, 1-indanone (8c), 7-fluoro-1-tetralone (8d), 7-fluoro-1-benzosuberone (8e) yielded mixtures of diastereomeric trimethylsilylated aminonitriles (1S,1′R)-14a-e/(1R,1′R)-14a-e. The addition proceeded with diastereofacial selectivities ranging from 1:2.9 to 1:25. The selectivity was found to be temperature and solvent dependent. The diastereomeric ratio (dr) of aminonitriles (1S,1′R)-14a/(1R,1′R)-14a increased in different solvents in the order methanol2Cl2 (1:2.5)32Cl 2. In the pure THF, toluene, CHCl3, or CH2Cl2 kinetic product mixtures were formed, whereas the presence of methanol led to thermally equilibrated product mixtures. This solvent dependent change of the product dr is interpreted with a change in the TMSCN addition mechanism. Hydrolysis of the aminonitrile mixtures (1S,1′R)-14a-c/(1R,1′R)-14a-c and oxidative cleavage of the auxiliary yielded 1a-c, which showed the (S)-configuration as the major isomer.
Spiro hydantoin aldose reductase inhibitors
Sarges,Schnur,Belletire,Peterson
, p. 230 - 243 (2007/10/02)
Sorbitol formation from glucose, catalyzed by the enzyme aldose reductase, is believed to play a role in the development of certain chronic complications of diabetes mellitus. Spiro hydantoin derived from five- and six-membered ketones fused to an aromatic ring or ring system inhibit aldose reductase isolated from calf lens. In vivo these compounds are potent inhibitors of sorbitol formation in sciatic nerves of streptozotocinized rats. Optimum in vivo activity is reached in spiro hydantoins derived from 6-halogenated 2,3-dihydro-4H-1-benzopyran-4-ones (4-chromanones). In 2,4-dihydro-6-fluorospirol[4H-1-benzopyran-4,4'-imidazolidine]-2',5'- ione, the activity resides exclusively in the 4S isomer, compound 115 (CP-45,634, USAN: sorbinil). This compound is currently being used to test, in humans, the value of aldose reductase inhibitors in the therapy of diabetic complications.
