Semisynthetic erythromycin antibiotics

Claim 2

A compound according to Claim 1 wherein R₂ is methyl.

Claim 3

11-deoxy-6-O-methylerythromycin A-11,12-(N-methoxyethoxypropyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-benzyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-cyclopropyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-(4-methyl)butyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-(2-dimethylamino)ethyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-aminoethyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-3-(3-aminopropyl)aminopropyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-(3-dimethylamino)propyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-2-(4-methylpiperazinyl)ethyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-alpha-aminopentanoyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-3-hydroxypropyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-2-hydroxyethyl) cyclic carbamate; 11-deoxy-6-O-methylerythromycin A-11,12-(N-2-(2-hydroxy)ethoxyethyl) cyclic carbamate; 11-deoxyerythromycin A-11,12-(N-3-hydroxypropyl) cyclic carbamate.

Claim 4

A pharmaceutical composition in unit dosage form, comprising a therapeutically effective amount of a compound according to any one of Claims 1-3 in combination with a pharmaceutical carrier.

Claim 5

Use of a compound according to any one of Claims 1-3 for preparing a drug for treating and preventing bacterial and other microbiological infections in humans and lower animals in need of such treatment.

Claim 6

A method or making compounds according to claim 1 comprising the steps of 1) reacting an erythromycin compound of the formula with an acylating agent to esterify the 2'-position with an acyl group or 2 to 20 carbon atoms: 2) reacting the product of step 1 with benzyloxycarbonyl chloroformate to form an 11,12-diol having a benzyloxycarbonyl group at the 4'' position: 3) reacting the protected diol compound from step 2 with excess NaN(TMS)₂ at a temperature of from about -40°C to about -20°C and excess carbonyl-diimidazole (CDI) at a temperature of from about 0°C to room temperature for a time sufficient to form a 12-acyl imidazole; 4) reacting the acyl imidazole of step 3 with ammonia or an amine of the formula NH₂R₃ where R₃ is hydrogen, hydroxy, straight or branched chain alkyl, straight or branched chain alkoxy, heteroalkyl, heteroaryl, substituted and unsubstituted phenyl, 1-naphthyl and 2-naphthyl, straight or branched chain acyl, or sulfonyl; 5) if R₁ is hydroxyl, removing the acyl group at the 2' position by methanolysis; and 6) removing the 4''-benzyloxycarbonyl group by reduction with hydrogen.