Method for preparing camptothecin derivatives

A method of preparing a compound of Formula (I), ##STR12## which comprises dihydroxylating a compound of Formula (II), ##STR13## wherein:

• R.sub.1 and R.sub.2, which may be the same or different, are independently selected from hydrogen, lower alkyl, (C.sub.3-7) cycloalkyl, (C.sub.3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, or alkoxy alkyl, or (--CH.sub.2 NR.sub.7 R.sub.8), wherein:
• i) R.sub.7 and R.sub.8, which may be the same or different, are independently selected from hydrogen, lower alkyl, (C.sub.3-7) cycloalkyl, (C.sub.3-7) cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, or lower alkoxy lower alkyl;
• or
• ii) R.sub.7 represents hydrogen, lower alkyl, (C.sub.3-7)cycloalkyl, (C.sub.3-7) cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, or lower alkoxy lower alkyl, and R.sub.8 represents --COR.sub.9,
• wherein:
• R.sub.9 represents hydrogen, lower alkyl, perhalo-lower alkyl, (C.sub.3-7)cycloalkyl, (C.sub.3-7) cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl;
• or
• iii) R.sub.7 represents hydrogen or lower alkyl;
• and R.sub.8 represents diphenyl-methyl or --(CH.sub.2).sub.t Ar
• wherein:
• t is 0 to 5 and Ar represents phenyl, furyl, pyridyl, N-methylpyrrolyl, imidazolyl optionally substituted with one or more substituents selected from hydroxy, methyl, halogen, and amino;
• or
• iv) R.sub.7 and R.sub.8 taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) ##STR14## wherein:
• Y represents O, S, SO, SO.sub.2, CH.sub.2 or NR.sub.10,
• wherein:
• R.sub.10 represents hydrogen, lower alkyl, perhalo lower alkyl, aryl, aryl substituted with one or more substituents selected from lower alkyl, lower alkoxy, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups or --COR.sub.11,
• wherein:
• R.sub.11 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more substituents selected from lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups;
• and
• R.sub.3 and R.sub.4 are independently selected from hydrogen, loyr alkyl, (C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, or alkoxy alkyl;
• or R.sub.3 and R.sub.4 taken together form a saturated 5 to 6 atom heterocyclic group of formula (IB) ##STR15## wherein, n represents the integer 1 or 2;
• or
• R.sub.3 represents --OCONR.sub.12 R.sub.13,
• wherein,
• R.sub.12 and R.sub.13, which may be the same or different, are independently selected from hydrogen, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted carbocyclic or heterocyclic group, with the proviso that when both R.sub.12 and R.sub.13 are substituted or unsubstituted alkyl groups, they may be combined together with the nitrogen atom, to which they are bonded, to form a heterocyclic ring which may be interrupted with --O--, --S-- and/or >N--R.sub.14 in which R.sub.14 is hydrogen, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted phenyl group, and
• R.sub.5 represents hydrogen or alkyl, and
• R.sub.6 represents hydrogen or alkyl, and
• pharmaceutically acceptable salts thereof.