CAMPTOTHECIN ANALOGS AND METHODS OF PREPARATION THEREOF

1 . A compound having the formula

in racemic form, enantiomerically enriched form or enantiomerically pure form;

wherein R 1 and R 2 are independently the same or different and are hydrogen, —C(O)R f wherein R f is an alkyl group, an alkoxy group, an amino group or a hydroxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, an acyloxy group, —OC(O)OR d , wherein R d is an alkyl group, —OC(O)NR a R b wherein R a and R b are independently the same or different, H, —C(O)R f , an alkyl group or an aryl group, a halogen, a hydroxy group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an amino group, —SR c , wherein R c is hydrogen, —C(O)R f , an alkyl group or an aryl group; or R 1 and R 2 together form a chain of three or four members selected from the group of CH, CH 2 , O, S, NH, or NR 15 , wherein R 15 is an C 1 -C 6 alkyl group;

R 3 is H, a halogen atom, a nitro group, an amino group, a hydroxy group, or a cyano group; or R 2 and R 3 together form a chain of three or four members selected from the group of CH, CH 2 , O, S, NH, or NR 15 , wherein R 15 is an C 1 -C 6 alkyl group;

R 4 is H, F, an amino group, a C 1-3 alkyl group, a C 2-3 alkenyl group, a C 2-3 alkynyl group, a trialkylsilyl group or a C 1-3 alkoxy group;

R 5 is a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group;

R 6 is —Si (R 8 R 9 R 10 ) or —(R 7 )Si(R 8 R 9 R 10 ), wherein R 7 is an alkylene group, an alkenylene group, or an alkynylene group; and R 8 , R 9 and R 10 are independently a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, an aryl group or a —(CH 2 ) N R 11 group, wherein N is an integer within the range of 1 through 10 and R 11 is a hydroxy group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SR c or a nitro group;

R 12 is H or —C(O)R f , —C(O)OR d or —C(O)NR a R b ;

R 13 is H, F or —CH 3 ; and

pharmaceutically acceptable salts thereof.

2 . The compound of claim 1 wherein R 2 and R 3 together form a group of the formula —O(CH 2 ) n O— wherein n represents the integer 1 or 2.

3 . The compound of claim 1 wherein R 5 is an ethyl group, an allyl group, a benzyl group or a propargyl group.

4 . The compound of claim 1 wherein R 13 is H.

5 . The compound of claim 4 wherein R 5 is an ethyl group.

6 . The compound of claim 5 wherein R 4 is H.

7 . The compound of claim 6 wherein R 8 and R 9 are methyl groups, R 10 is a tert-butyl group or a methyl group, R 1 is H and R 3 is H.

8 . The compound of claim 7 wherein R 2 is H, NH 2 or OH.

9 . A compound having the formula

wherein R 5 is a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group;

R 12 is H or —C(O)R f , —C(O)OR d or —C(O)NR a R b .

10 . The compound of claim 9 wherein R 5 is an ethyl group, an allyl group, a benzyl group or a propargyl group.

11 . The compound of claim 10 wherein R 5 is an ethyl group.

12 . A compound having the formula

wherein R 5 is a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group;

R 13 is H, F or —CH 3 ; and

R 15 is a C 1 -C 6 alkyl group.

13 . The compound of claim 12 wherein R 5 is an ethyl group, an allyl group, a benzyl group or a propargyl group.

14 . The compound of claim 13 wherein R 13 is H.

15 . The compound of claim 14 wherein R 5 is an ethyl group.

16 . A compound having the formula

in racemic form, enantiomerically enriched form or enantiomerically pure form;

wherein X is a radical precursor;

R 5 is a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group;

R 6 is an alkyl group, —Si(R 8 R 9 R 10 ) or —(R 7 ) Si(R 8 R 9 R 10 ), wherein R 7 is an alkylene group, an alkenylene group, or an alkynylene group; and R 8 , R 9 and R 10 are independently a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, an aryl group or a —(CH 2 ) N R 11 group, wherein N is an integer within the range of 1 through 10 and R 11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SR c or a nitro group; and

R 13 is H, F or —CH 3 .

17 . The compound of claim 16 wherein R 5 is an ethyl group, an allyl group, a benzyl group or a propargyl group.

18 . The compound of claim 17 wherein X is Br or I.

19 . The compound of claim 18 wherein R 13 is H.

20 . The compound of claim 19 wherein R 5 is an ethyl group.