Potent, simplified derivatives of pateamine A

1. A compound of the formula:

and its pharmaceutically accepted salts, wherein

A—B is ethane, (E) and (Z)-ethene, (E) and (Z)-substituted ethene, ethyne,

K is hydrogen or one-to-three carbon alkyl group,

Q═NH or O,

X is hydrogen, hydroxy, alkoxy, alkyl, aminocarbonyl, amino, alkylamino, dialkylamino, alkoxycarbonylamino,

Y is S, NH, or O,

Z is hydrogen, hydroxy, aminocarbonyl, alkylamino, dialkylamino, alkoxycarbonylamino, but not t-butoxycarbonylamino when R 4 is dimethylamino,

R 1 is hydrogen or one-to-three carbon alkyl group, and

R is selected from the following:

(a) Alkene of the formula:

wherein R 2 is optionally substituted with one or more substituents selected from alkyl, alkylhydroxy, alkylalkoxy, alkylamino, alkylaminoalkyl, or alkylaminodialkyl;

(b) Alkenylaryl of the formula:

wherein R 3 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, trifluoromethane, or fluoro; and

(c) Methyldienylpentyl of the formula:

wherein R 4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino; and

(d) Methylalkenylpentyl of the formula:

wherein R 4 is optionally substituted with one or more substituents selected from hydrogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, amino, alkylamino, or dialkylamino.

2. A compound of the formula:

and its pharmaceutically accepted salts.

3. A compound of the formula:

and its pharmaceutically accepted salts, wherein R 1 is selected from hydroxyalkene, methoxyalkene, dimethyl amino alkene; and dimethyl amino methyldiene.

4. A compound of the formula:

and its pharmaceutically accepted salts.

5. A compound of the formula:

and its pharmaceutically accepted salts.

6. A compound of the formula:

and its pharmaceutically accepted salts.

7. A compound of the formula:

and its pharmaceutically accepted salts.

8. A compound of the formula:

and its pharmaceutically accepted salts.

9. A compound of the formula:

and its pharmaceutically accepted salts.

10. A compound of the formula:

and its pharmaceutically accepted salts.

11. A compound of the formula:

and its pharmaceutically accepted salts, wherein

X═O, NH or NR; and

Y═O, NH or NR, where R is alkyl or aryl group.

12. A method of making a biotinylated derivative of PatA, comprising the steps of:

13. A method of synthesis of DMDA Pat A comprising the steps of:

, wherein a indicates treatment with trichloroethanol and thionyl chloride in benzene at reflux for 5 hours; b indicates treatment with bromine in a chloroform/carbon tetrachloride co-solvent mixture at 0 degrees C. for 3 hours; c indicates treatment with 2,6-lutidine in dichloromethane at 25 degrees C. for 12 hours followed by trifluoroacetic anhydride, pyridine and Hünig's base from 0 to 25 degrees C. for 3 hours; d indicates treatment with tetrabutylammonium fluoride and 20 mol % acetic acid in tetrahydrofuran at −20 degrees C. for 1 hour for compound 10 and 25 degrees C. for 12 hours for compound 13; e indicates treatment with a triphenylphosphine and diisopropyl azodicarboxylate in tetrahydrofuran at −20 degrees C. for 2 hours; f indicates treatment with 10% cadmium/lead couple in tetrahydrofuran/1M ammonium acetate at 25 degrees C. for 2 hours; g indicates treatment with 2,4,6-trichlorobenzoyl chloride, triethylamine and dimethylaminopyridine in toluene/tetrahydrofuran (0.001 M) co-solvent mixture at 25 degrees C. for 2 hours; h indicates treatment with palladium with calcium carbonate poisoned with lead and hydrogen gas in methanol at 25 degrees C. for 12 hours; and indicates treatment with 10 mol % [palladium dibenzylidene acetone.chloroform complex:arsine in 1:8 ratio] and compound 17 in tetrahydrofuran at 25 degrees C. for 2 hours.