Total synthesis of the proposed structure of 8-deshydroxyajudazol a: A modified approach to 2,4-disubstituted oxazoles

The total synthesis of the proposed structure for the minor myxobacterial metabolite 8-deshydroxyajudazol A (3) is described. The isochromanone moiety present in the eastern fragment was constructed by an intramolecular-Diels–Alder (IMDA). Difficulties were encountered with the formation of the 2,4-disubstituted oxazole, so this was synthesized via a modified approach. This involved selective acylation of the diol 7 with acid 8, azide displacement of the secondary alcohol, and subsequent azide reduction in the presence of base which induced an O,N shift to give the hydroxyamide 23. Cyclodehydration then gave the desired oxazole 24 and deprotection followed by mesylation and elimination produced the C15 alkene 5. Sonogashira coupling with the eastern fragment vinyl iodide 6 and partial reduction yielded 8-deshydroxyajudazol A (3).