125876-15-5Relevant academic research and scientific papers
Asymmetric synthesis with 6-tert-butyl-5-methoxy-6-methyl-3,6-dihydro-2H-1,4-oxazin-2-one as a new chiral glycine equivalent: Preparation of enantiomerically pure α-tertiary and α-quaternary α-amino acids
Koch, Claus-Juergen,Simonyiova, Sona,Pabel, Joerg,Kaertner, Annerose,Polborn, Kurt,Wanner, Klaus Theodor
, p. 1244 - 1263 (2007/10/03)
The chiral oxazinone 2 has been developed as a new chiral glycine equivalent for the asymmetric synthesis of mono- and disubstituted α-amino acids. It is derived from the α-hydroxycarboxylic acid 1, which serves as a chiral auxiliary, and is easily accessible in enantiomerically pure form by optical resolution of the racemic compound (RS)-1. For alkylation reactions, 2 was deprotonated with sBuLi or phosphazenic base. Subsequent treatment with alkyl halides yielded the monosubstituted compounds 13/14a-c, e, f, (ent)-13d, (ent)-14d, while a second alkylation step, via the corresponding enolates, provided the disubstituted compounds 17/18a-d. Both alkylation steps proceeded with good yields and excellent diastereoselectivities (up to 99% de) and even less reactive electrophiles such as isopropyl iodide could be used. The results obtained in this reaction supported the assumption that the enolate of 2, as well as those of the monosubstituted derivatives of 2, have less tendency to form the aggregates that hamper alkylation reactions with other systems with higher oxygen content. From the major diastereomers of both the mono- and the disubstituted derivatives of 2 the corresponding α-amino acids 33a-c and 34a-d were obtained in high enantiomeric purity by hydrolytic cleavage of the oxazinone ring, accomplished either in two steps with aqueous TFA and aqueous NaOH or in one with either aqueous NaOH or 3 N HBr. Alkylation of the enolate ions of (S)-2 or (R)-2 with epichlorohydrins as bifunctional electrophiles provided the hydroxymethylenecyclopropyl derivatives 21 and 22. Hydrolysis of 21 and 22 afforded the free amino acids 35 and (ent)-35. Reductive amination with aniline after oxidation of 21 and 22 to the corresponding aldehydes 24 and 26 provided the compounds 25 and 27, whereas Mitsunobu treatment of 21 and 22 with 1-phenyl-3-(trifluoroacetyl)urea (28) afforded the urea derivatives 29 and 31. Hydrolysis of these compounds yielded the corresponding 1-aminocylopropanecarboxylic acid derivatives 36/(ent)-36 and (ent)-37. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Enantioselective total syntheses of cyclopropane amino acids: Natural products and protein methanologs
Jimenez, Jose M.,Rife, Joan,Ortuno, Rosa M.
, p. 537 - 558 (2007/10/03)
The syntheses of (-)-allo-coronamic acid, (-)-allo-norcoronamic acid, (-)-(Z)-2,3-methanohomoserine, (-)-(Z)-2,3-methanomethionine, and (2S,3R)-Cbz-cyclo-Asp-OMe have been achieved in 45-68% overall yields from suitable intermediates derived from homochiral aminopentenoates which were obtained, in turn, from D-glyceraldehyde. The key synthetic step involves the quantitative and highly diastereoselective cyclopropanation of such precursors. The factors dealing with the control of stereoselectivity are highlighted and the main features in side-chain functionalization to the respective target molecules are discussed.
Enantioselective Total Syntheses of (-)-allo-Coronamic Acid, (-)-(Z)-2,3-Methanohomoserine, and (2S,3R)-Cbz-cyclo-Asp-OMe
Jimenez, Jose M.,Rife, Joan,Ortuno, Rosa M.
, p. 1849 - 1852 (2007/10/03)
The title amino acids have been synthesized in 45, 47, and 63percent overall yields, respectively, from enantiopure aminopentenoates, easily available from D-glyceraldehyde as a source of chirality, following divergent pathways from similar diols as commo
Asymmetric Synthesis of 2,3-Methanohomoserine: A General Approach to Chiral 2-Substituted Cyclopropane Amino Acids
Aitken, David J.,Royer, Jacques,Husson, Henri-Philippe
, p. 2814 - 2820 (2007/10/02)
Double deprotonation-alkylation of the chiral aminonitrile synthon (R)-N-(cyanomethyl)-4-phenyloxazolidine (1) with LDA-HMPA and either epibromohydrin or glycidyl triflate gave in good yield the 2-(hydroxymethyl)cyclopropyl derivative in which two of the four possible diastereoisomeric forms predominated.A combination of simple chemical transformations of the cyclopropane C-1 substituents and chromatographic separation furnished two optically pure 2,3-methanohomoserines, functionalized as the methyl ester 11a and the γ-lactone 10b, respectively.These compounds can be converted into the free amino acids upon treatment with aqueous base and are proposed as useful intermediates in the asymmetric synthesis of other cyclopropane amino acids through subsequent manipulation of the 2-hydroxymethyl substituent.
