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

wherein R 13 is H, F or —CH 3 ; and

R 14 is SiMe 3 , I, or Br.

2. A method of synthesizing a compound having the following formula:

wherein Y is Cl, Br or I;

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 , comprising the steps of

(a) treating an enol ether of the structure:

under suitable oxidative cleavage conditions to form a compound having the structure:

(b) treating the compound formed in step (a) with an organometallic reagent having the structure:

MC(R 13 )(R 13 )CO 2 R 15

wherein M is Li, Na, K, MgY, or ZnY, and R 15 is a C 1 -C 6 alkyl group under suitable conditions to form a compound having the structure:

(c) treating the compound formed in step (b) under suitable conditions with acid to form a compound having the structure:

(d) treating the compound formed in step (c) under suitable conditions of halogenative desilylation to form a compound having the structure:

(e) treating the compound in step (d) with acid or iodotrimethylsilane under suitable conditions for demethylation to provide a compound of the following structure:

(f) treating the compound in step (e) with a lithium base or a sodium base in the presence of an inorganic lithium salt to deprotonate the nitrogen atom,

(g) reacting of the resulting deprotonated species of step (f) with a compound of the following structure:

wherein Z is I, Br, Cl, a mesylate group, or a tosylate group, and under suitable conditions to cause the formation of the compound of the following structure:

3. The method of claim 2 wherein R 5 is an ethyl group, an allyl group, a benzyl group or a propargyl group.

4. The method of claim 3 wherein R 13 is H.

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