Intermediates and methods for synthesizing calicheamicin derivatives

1. A compound of Formula I

wherein R 12 is selected from straight and branched-chain C 1 -C 8 alkyl;

each R 10 is independently selected from hydrogen, R 12 and —OR 12 ;

R 8 and R 9 are each independently selected from hydrogen and straight and branched-chain C 1 -C 8 alkyl, wherein each said alkyl for R 8 and R 9 is independently optionally substituted by —NH 2 , —NHR 11 , —NR 11 R 13 , —OR 11 , —OH, or —SR 11 , wherein each R 11 and each R 13 are independently selected from straight and branched-chain C 1 -C 5 alkyl;

r is an integer 0 or 1;

G is oxygen or sulfur;

Z 1 is H or straight or branched-chain C 1 -C 5 alkyl;

Ar is 1,2-, 1,3-, or 1,4-phenylene optionally substituted with one, two or three groups independently selected from straight or branched-chain C 1 -C 6 alkyl, —OR 14 , —SR 14 , halogen, nitro, —COOR 14 , —C(═O)NHR 14 , —O(CH 2 ) n COOR 14 , —S(CH 2 ) n COOR 14 , —O(CH 2 ) n C(═O)NHR 14 , and —S(CH 2 ) n C(═O)NHR 14 , or Ar is a 1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7-, 1,8-, 2,3-, 2,6-, or 2,7-naphthylidene optionally substituted with one, two, three, or four groups independently selected from straight or branched-chain C 1 -C 6 alkyl, —OR 14 , —SR 14 , halogen, nitro, —COOR 14 , —C(═O)NHR 14 , —O(CH 2 ) n COOR 14 , —S(CH 2 ) n COOR 14 , —O(CH 2 ) n C(═O)NHR 14 , and —S(CH 2 ) n C(═O)NHR 14 ;

wherein each R 14 is independently selected from (C 1 -C 5 )alkyl and each R 14 is independently optionally substituted with one or two groups selected from —OH, —(C 1 -C 4 )alkyl, and —S(C 1 -C 4 )alkyl;

each n is an integer independently selected from 0, 1, 2, 3, 4, and 5;

W is selected from —O—, —S—, —C(═O)NH—, —NHC(═O)—, and —NR 15 —, wherein R 15 is a (C 1 -C 5 )alkyl and R 15 is optionally substituted with one or two groups selected from —OH, —(C 1 -C 4 )alkyl, and —S(C 1 -C 4 )alkyl; and

Y is a straight or branched-chain (C 1 -C 6 )alkylene group or a straight or branched-chain (C 2 -C 6 )alkenylene group.

2. A compound of claim 1 , wherein each R 10 is hydrogen.

3. A compound of claim 2 , wherein R 12 is methyl.

4. A compound of claim 3 having the structure

5. A compound of claim 1 , wherein R 8 and R 9 are methyl, r is 0, G is oxygen, Z 1 is methyl, Ar is 1,4-phenylene, W is —O—, and Y is —(CH 2 ) 3 —.