NEW COMPOUNDS OF THE MANUMYCIN GROUP OF ANTIBIOTICS AND A FACILITATED ROUTE FOR THEIR STRUCTURE ELUCIDATION

Manumycin B (2) and C (3) are structural analogs of manumycin A (1), the main metabolite of Streptomyces parvulus (strain Tu 64). The new minor components vary within the polyketide assembling of the acylamino side chain and the stereochemistry at C-4 in the central mC7N unit. Apart from unreported stereochemical details 2 and 3 resemble the recently found UCF1-A and -B, inhibitors of ras farnesyltransferase. Manumycin D (4) is the first of the manumycin type compounds without an oxirane in the mC7N unit. The relative stereochemistry in the mC7N unit of 2-4 was elucidated with proton NMR spectroscopy using different ASIS (aromatic solvent induced shift) effects on the olefinic 3-H. In combination with the established circular dichroism (CD) spectroscopy the absolute stereochemistry of the whole mC7N unit was determined without chemical degradation.