A-Amino /J-hydroxy acids

Oxazolines are versatile intermediates in the synthesis of jS-substituted serines which are of significant importance because of their utility in the synthesis of various antibiotics [132]. Thus, the serine moiety constitutes the primary core structure of antibiotics, such as hypeptin and leucinostatin. Ethyl isocyanoac-etate, a synthon for the formation of oxazolines, is relatively acidic and can be deprotonated by a variety of bases for coupling with aldehydes to afford oxazolines. However, the lack of diastereoselectivity of such reactions has rendered this synthetic route of limited use and as a result, alternate routes to the jS-hydroxy-a-amino acids have been developed which, however, are also not entirely satisfactory. 

Several synthetic methods have appeared in which derivatives of amino-acids have been reacted with strong base and then with carbon electrophiles. This process has been used in the a-hydroxymethylation of SchifI bases derived from a-amino-acid esters and good yields of /3-hydroxy-a-amino-acids are obtained. This type of compound is also prepared using the optically active imine (183) the t/trco-product was obtained with selectivity ranging from 58 to 92% and optical purity between 43 and 71% (Scheme 88). The jS-hydroxy-a-amino-acid (185) is a constituent of the antibiotic bleomycin and its preparation from L-rhamnose has been described. Studies on the asymmetric synthesis of amino-acids by alkylation of various lactim ethers (186) have continued. L-Alanine, L-valine, and (S)-0,0-dimethyl-a-methyldopa have been used to prepare the heterocyclic intermediates (186), which give a range of amino-acids in high yield and enantiomeric excess. Earlier work has also been extended to the alkylation of the imidazolone anion (187). ... 

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