228717-06-4Relevant academic research and scientific papers
Stereoselective syntheses of protected β-hydroxy-α-amino acids using (arylthio)nitrooxiranes
Adams, Zoe M.,Jackson, Richard F. W.,Palmer, Nicholas J.,Rami, Harshad K.,Wythes, Martin J.
, p. 937 - 947 (2007/10/03)
The scope and limitations of a method for the stereocontrolled synthesis of a range of protected β-hydroxy-α-amino acids have been established. The method comprises condensation of a chiral, enantiomerically pure aldehyde 6 with (4-methylphenylthio)nitromethane 7 to form a 1-arylthio-1-nitroalkene 8; stereoselective epoxidation of this alkene with a metal alkyl peroxide; and stereospecific reaction of the arylthionitrooxirane with a nitrogen nucleophile to give an α-amino thioester. This method has been employed in the synthesis of protected derivatives of both diastereoisomers of threonine 1 and 2, and of β-hydroxyleucine 3 and 4 and a synthesis of the anti-diastereoisomer of β-phenylserine 5.
A New Approach to the Synthesis of β-Hydroxy-α-amino Acids Using (Arylthio)nitrooxiranes
Jackson, Richard F. W.,Palmer, Nicholas J.,Wythes, Martin J.,Clegg, William,Elsegood, Mark R. J.
, p. 6431 - 6440 (2007/10/03)
2-(Arylthio)-2-nitrooxiranes, prepared by the nucleophilic epoxidation of 1-(arylthio)-1-nitroalkenes using anhydrous metal alkyl peroxides in tetrahydrofuran, react with aqueous ammonia to give α-amino thioesters in good yield, without significant formation of the primary amide by subsequent reaction of the thioester with ammonia.In situ protection of the amino group is possible, leading to a range of protected derivatives.Diastereoselective epoxidation of 1-(arylthio)-1-nitroalkenes with an allylic, oxygen-substituted stereogenic center using metal alkyl peroxides is possible, and the sense of diastereoselectivity can be controlled simply by use of lithium or potassium as the counterion.Enhanced syn selectivity (15:1) in lithium tert-butyl peroxide mediated epoxidations can be achieved by using toluene as solvent.Use of potassium triphenylmethyl peroxide, rather than potassium tert-butyl peroxide, generally gives higher anti selectivity (12:1).Reactions of enantiomerically and diastereomerically pure 2-(arylthio)-2-nitrooxiranes with ammonia proceed stereospecifically with inversion of configuration, establishing a stereocontrolled route to β-hydroxy-α-amino acids.Use of other nitrogen nucleophiles, for example amino acid esters, is also possible, leading to a stereospecific approach to α-amino dicarboxylic acids.Applications of this methodology, which constitutes a stereocontrolled Strecker reaction, to the synthesis of γ-hydroxy threonine derivatives 19-22, polyoxamic acid (26), and the C-5 epimer of the sugar fragment of polyoxin C (27) are described.
