Chemical modification of thiangazole A in the oxazole and styryl region

The partial synthesis of 54 derivatives of thiangazole A (la), a new polyth iazoline antibiotic from Polyangium spec. (myxobacteria), is described. Der ivatives with chemical modification of the carboxamide group in the oxazole region were prepared either by N-alkylation to amides 5-14 or by methanoly sis to ester 15, and its transformation products 16, 19, 20. Oxidation of t he C-5 methyl group of la with molecular oxygen led to the hydroxymethyl de rivative 21, and two by-products lacking the C-5 methyl group (22), or the entire oxazole ring (23). Key intermediate for analogues with modifications in the styryl region is the aldehyde 27, obtained by direct cleavage of th e C-21/C-22 double bond. 27 was transformed into the oximes 37-42 and by Wi ttig reaction to (21Z)-thiangazole (43) and analogues 44-46 with proton and alkyl residues replacing phenyl. 21,22-Didehydrothiangazole (50) was synth esized in a multi-step reaction from 27 via the 20-alkinyl intermediate 49. The insecticidal activities and inhibition of the respiratory chain (compl ex I) by the thiangazole analogues were determined and compared with the na tural product.