SYNTHESIS OF PHOSPHONIC-ACIDS RELATED TO THE ANTIBIOTIC FOSMIDOMYCIN FROM ALLYLIC ALPHA-HYDROXYPHOSPHONATES AND GAMMA-HYDROXYPHOSPHONATES

Pd(0) catalyzed amination of dialkyl (1-methoxycarbonyloxy-2-alkenyl)p hosphonates 4 (R(3) = H) with the N,O-alkoxycarbonyl protected hydroxy lamines BocNHOBoc (3a) and MocNHOMoc (3b) proceeds regiospecifically a nd with high (E)-stereoselectivity to give the protected (3-N-hydroxya mino-1-alkenyl)-phosphonates 5 and 6, respectively, with very good yie lds. Alternatively compounds 5 and 6 are obtained in excellent yields from the (3-hydroxy-1-alkenyl)phosphonates 2 under Mitsunobu condition s using 3a and 3b, respectively, as nucleophiles. Much less satisfacto ry yields of compounds 7 and 8 have been obtained in both pathways usi ng the hydroxylamine derivatives BocNHOBn (3c), and AcNHOAc (34), resp ectively, as nucleophiles. Compounds 5-8 have been further transformed to various precursors and analogues of the natural phosphonic acid an tibiotics FR 32863 and FR 31564 (fosmidomycin).