Total Synthesis of Agrocin 84 and Phosmidosine as Naturally Occurring Nucleotidic Antibiotics Having P-N Bond Linkages.

Abstract

This review deals with our recent studies of the synthesis of naturally occurring nucleic acid derivatives having P-N linkages. The total synthesis of a nucleotidic antibiotic, agrocin 84 (1), having two different types of unique phosphoramidate bonds is described in detail. Synthesis of this natural product remained unrealized for a long time after its discovery in 1974, but development of a new method for the construction of the P-N bond led us to our final goal. Phosmidosine (2) is an antibiotic that has an antifungal activity and has a rare O-methylated phosphoramidate structure. This compound was also successfully synthesized by use of 5-(3, 5-dinitrophenyl)-1H-tetrazole (DNPT) as the powerful activator of an N-prolyl phosphorodiamidite derivative that was condensed with an 8-oxoadenosine derivative. Several related compounds were also synthesized. These phosmidosine derivatives were found to exhibit significant antitumor activities. In connection with these studies, the synthesis and biological properties of aminoacylamido-AMP derivatives having N-P bonds as stable analogues of aminoacyl-AMP are also described.