GB1467401A - Kanamycin derivatives - Google Patents

Abstract

1467401 Acylated kanamycins BRISTOLMYERS CO 22 Feb 1974 [23 Feb 1973 (2)] 8193/74 Addition to 1401221 Heading C2C Novel acylated kanamycins of the general formula wherein R<SP>3</SP> is OH or NH 2 and R<SP>2</SP> is L-(-)-#- amino - α - hydroxypropionyl or L - (-) - 8- amino-α-hydroxyvaleryl, and pharmaceutically acceptable acid addition salts thereof, are prepared by reacting kanamycin A or B (1 mole) with a compound having one of the following general formulµ wherein each of R<SP>4</SP> and R<SP>5</SP> is H, F, Cl, Br, NO 2 , OH, alkyl or alkoxy and X is Cl, Br or I (up to 1 mole) at below 50‹ C., acylating the resulting N-substituted kanamycin of the general formula wherein Y is a group having one of the following general formulµ with a compound of the general formula WNH(CH 2 ) n CH(OH)COM, wherein n is 1 or 3, W is as Y and M is a group having one of the following formulµ (molar ratio 1 : at least 0À5) and removing the blocking groups W and Y from the resulting di-N-substituted kanamycin of the general formula followed optionally by salification of the product. The N-hydroxysuccinimide esters of L-#- benzyloxycarbonylamino - α - hydroxypropionic and L - # - benzyloxycarbonylamino - α - hydroxyvaleric acid are prepared by reacting L-#-amino- α-hydroxypropionic acid or L-#-amino-α-hydroxyvaleric acid with carbobenzoxy chloride in the presence of NaOH and reacting the resulting benzyloxycarbonylamino derivative with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide. N-Bemyloxycarbonyloxy-succinimide is prepared by reacting N-hydroxysuccinimide with carbobenzoxy chloride in the presence of NaOH. Pharmaceutical compositions having antibacterial activity comprise, as active ingredient, an acylated kanamycin of the first general formula above or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier.