CONVENIENT ROUTE TO GAMMA-NITRO-ALPHA-AMINO ACIDS - CONJUGATE ADDITION OF NITROALKANES TO DEHYDROALANINE DERIVATIVES

gamma-Nitro-alpha-amino acid derivatives are obtained in good yield fr om the base-catalysed conjugate addition of nitroalkanes to N-protecte d dehydroalanine eaters (methyl 2-amidoacrylates). The outcome of the reaction is dependent on the N-protecting group (the ease of the produ ct formation correlates with the electron-withdrawing ability and henc e stabilising effect on the adduct alpha-anion of the 2-substituent in the order phthalimido > benzyloxycarbonylamino > acetamido), the nitr oalkane, and on the reaction conditions. Conditions were established i n reactions of methyl 2-phthalimidoacrylate 4 with nitromethane for se lectively obtaining 1:1-, 2:1- or 3:1-adducts. Good yields of the 1:1- adducts are obtained when the reaction is carried out with an excess o f nitroalkane. Restricting the amount of nitromethane gives rise to th e higher adducts. Similarly, reactions of 4 with nitroethane can be ad justed to give 1:I-or 2: l-adducts selectively. These reactions occur with little or no diastereoselectivity. As a model for a dehydroalanin e residue in a peptide chain, the diamide N-cyclohexyl-2-acetamidoacry lamide 7 has been prepared. This dehydroalanine reacts with 2-nitropro pane and with nitromethane in refluxing tert-butyl alcohol to give rea sonable yields of 1:1-adducts. As the nitro group of the resultant gam ma-nitro-alpha-amino acid derivatives can be transformed into a variet y of other functionalities, the methodology described in this paper of fers a versatile entry to a range of gamma-substituted alpha-amino aci ds.