Stereochemical elucidation and total synthesis of dihydropacidamycin D, a semisynthetic pacidamycin

Hydrogenation of the C(4') exocyclic olefin of the pacidamycins has been sh own to produce a series of semisynthetic compounds, the dihydropacidamycins , with antimicrobial activity similar to that of the natural products. Eluc idation of stereochemistry in the pacidamycins has been completed through a campaign of natural product degradation experiments in combination with th e total synthesis of the lowest-molecular weight dihydropacidamycin, dihydr opacidamycin D. The stereochemical identities of the tryptophan and two ala nine residues contained in pacidamycin D have been shown to be of the natur al (S) configuration, and the unique 3-methylamino-2-aminobutyric acid cont ained in this series of antibiotics has been shown to be of the (2S,3S) con figuration. Finally, the stereochemistry obtained by hydrogenation of the C (4')-C(5') exocyclic olefin has been shown to be (R) at the C(4') nucleosid e site.