Camptothecin intermediates and method of making camptothecin and

Details Camptothecin intermediates and method of making camptothecin and Camptothecin intermediates and method of making camptothecin and

1993-08-31

1995-12-12

Daus, Donald G.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546 48, 546153, 546180, C07D491052

Patent

active

054751080

ABSTRACT:
Disclosed are new methods of making camptothecin and camptothecin analogs defined by Formula I: ##STR1## wherein R is loweralkyl; R.sub.1 is H, loweralkyl, loweralkoxy, or halo; and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently H, amino, hydroxy, loweralkyl, loweralkoxy, loweralkylthiol, di(loweralkyl)amino, cyano, methylenedioxy, formyl, nitro, halo, trifluoromethyl, aminomethyl, azido, amido, hydrazino, or any of the twenty standard amino acids bonded to the A ring via the amino-nitrogen atom. The methods comprise cyclizing a compound of Formula IV: ##STR2## wherein X is Br or I, and Y is H, by an Aryl-to-Aryl free radical coupling reaction to yield a compound of Formula I. Compounds of Formula IV are made by alkylating a compound of Formula III: ##STR3## wherein R is loweralkyl and Y is H with a compound of Formula II-x: ##STR4## wherein X is a Br or I and V is hydroxy, by a Mitsunobu reaction to yield the compound of Formula IV.

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