SYNTHESIS OF SAFRAMYCINS .11. SYNTHETIC STUDIES TOWARD A TOTAL SYNTHESIS OF SAFRACIN-A

A synthetic strategy for the preparation of the isoquinolinequinone antibiotic safracin A (1a) is outlined. Our initial strategy for the construction of the ABC ring was based on a retrosynthetic analysis. Conversion of 5 in five steps to the imide 16 was followed by a 1,2-reduction with lithium tri-tert-buroxyaluminum hydride to give the allylic alcohol 7a. This compound was then cyclized to the 1,5-imino-3-benzazocine 8a and the indeno[1,2-b]pyrazin-2-one 17. An unwanted isomer 17 was converted to the N-methyl tetracyclic lactam 21, the structure of which was determined by X-ray crystallography. Conversion of 18 to the pentacyclic pyruvamide 31 was completed in a nine step sequence. Finally, 31 was subjected to a two-step oxidative demethylation to provide the quinones 10a and 34. An unsuccessful attempt to introduce a hydroxyl group onto the C-l position of the quinones 10a or 34 is also described.