TOTAL SYNTHESIS AND STRUCTURE ASSIGNMENT OF THE ANTITUMOR ANTIBIOTIC ARANOROSIN

The structurally unique antifungal and antitumor antibiotic aranorosin was prepared in a convergent, stereoselective sequence. Oxidative cyc lization of N-protected L-tyrosine, followed by face-selective 1,2-add ition of [(benzyloxy)methyl]lithium, Henbest oxidation in the presence of Kishi's radical inhibitor, and simultaneous N,O-deprotection led t o an amino diol which was N-acylated with the fatty acid side-chain se gment. After a low-temperature reduction of the lactone moiety to the lactol, the carbonyl function was regenerated under neutral conditions by diol cleavage with sodium periodate. Preparation of the acid side chain involved a diastereoselective imide alpha-alkylation directed by Evans' oxazolidinone auxiliary, followed by a series of Wittig-Horner chain extensions. Since the relative configuration at the C (6') posi tion of the natural product had not been determined, we prepared both the (6'S) and the (6'R) isomers of aranorosin. Comparison of synthetic material with the reported spectral data for natural (-)-aranorosin, especially H-1 and C-13 NMR and [alpha]D, did not allow a definitive a ssignment. After purification of a sample of the isolated material fro m Pseudoarachniotus roseus, the corrected [alpha]D strongly indicated the (6'R)-stereochemistry for the natural compound. This assignment wa s confirmed by circular dichroism spectra for (6'S)- and (6'R)-aranoro sin and the natural material.