PF-1163B

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

The total synthesis of (-)-PF1163A and B (I, R = β-OH, H) from Boc-L-tyrosine and (R)-citronellol was accomplished and their absolute configurations determinedConversion of the protected intermediate from Boc-L-tyrosine with β-naphthoyl chloride to the mixed anhydride followed by reaction of II gave III which after removal of all protecting groups yielded an amino acid which was cyclized by Bop-Cl to give 62% of (-)-PF1163B.(-)-PF1163A was prepared via similar strategy and both were identical to the natural antibiotics in all respects.