TOTAL SYNTHESIS OF (+/-)-PYRIDOXATIN

An efficient two-step route to pyridoxatin analogues 13 and 15 has been developed. Condensation of 4-hydroxypyridone (4) with citronellal (10) affords o-quinone methide intermediate 11, which reacts further to give inverse electron demand Diels-Alder adducts 12 and 16 and ene adduct 14. Oxidation of 12 and 14 with MoO5 by Sammes' procedure completes the synthesis of 13 and 15. Using this approach, the first total synthesis of(+/-)-pyridoxatin (1) has been carried out in seven steps from cis-2,4-dimethylcyclohexanone (21). The key step is the condensation of 4-hydroxypyridone (4) with the allylic silane aldehyde 26 to give 35% of cyclohexylpyridones 2 and 30.