Total synthesis and structure assignment of the antitumor antibiotic aranorosin

Article abstract of DOI:10.1021/jo00077a050

The structurally unique antifungal and antitumor antibiotic aranorosin was prepared in a convergent, stereoselective sequence. Oxidative cyclization of N-protected L-tyrosine, followed by face-selective 1,2-addition of [(benzyloxy)methyl]lithium, Henbest oxidation in the presence of Kishi's radical inhibitor, and simultaneous N,O-deprotection led to an amino diol which was N-acylated with the fatty acid side-chain segment. 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 α-alkylation directed by Evans' oxazolidinone auxiliary, followed by a series of Wittig-Horner chain extensions. Since the relative configuration at the C(6') position 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 ¹H and ¹³C NMR and [α](D), did not allow a definitive assignment. After purification of a sample of the isolated material from Pseudoarachniotus roseus the corrected [α](D) strongly indicated the (6'R)-stereochemistry for the natural compound. This assignment was confirmed by circular dichroism spectra for (6'S)- and (6'R)-aranorosin and the natural material.