Conformationally constrained serine analogues: Synthesis of new 2-amino-3-hydroxynorbornanecarboxylic acid derivatives

A synthesis of the new oxazolone 2, functionalized with the ethoxycarbonylo xy group on methylenic carbon, is presented, starting from 4-hydroxymethyle noxazolone 1 and ethyl chlorocarbonate. Oxazolone 2 was reacted with cyclop entadiene in the presence of EtAlCl2, giving the two diastereoisomeric cycl oadducts exo-3 and endo-3 in a 70:30 ratio. Selective hydrolysis of the lac tone ring (THF, HCl) gave the corresponding acids 5 and 6 which were transf ormed into hydroxyacid derivatives 7 and 8, respectively, operating in an e thanolic solution of Me2NH. The new 3-hydroxy2-aminonorbornane-2-carboxylic acids 11 and 12, in which the serine skeleton is included, were obtained b y reduction of acids 5 and 6 to derivatives 9 and 10 and a subsequent hydro lysis with HCl.