Nitric Acid → Rubitecan

Participants

Reaction Steps

It was also found that when camptothecin in sulfuric acid was treated carefully with nitric acid under ice-cooling and agitation, new 9-nitrocamptothecin could be obtained in a yield of 30-40% together with the known 12-nitrocamptothecin. This new 9-nitrocamptothecin is then reduced to 9-aminocamptothecin which can be converted into various 9-substituted camptothecin derivatives according to the methods known per se as in the case of 10-nitrocamptothecin (Japanese Laid-open Patent Appln. No. 59-51289). For example, 9-aminocamptothecin can be converted into the corresponding 9-halogeno or 9-cyano derivative by once converting the 9-amino derivative into 9-diazonium salt and then treating the salt with cuprous halide or cyanide according to the Sandmayer reaction. Further, 9-diazonium salt can be converted into 9-hydroxy, 9-alkoxy and 9-acyloxy derivatives in the manner known per se.

Provenance & Evidence