SE8007540L - aminocyclitols - Google Patents

Abstract

1529376 Aminocyclitol antibiotics STERLING DRUG Inc 9 Feb 1976 [18 Feb 1975 22 Sept 1975] 04973/76 Heading C2C Novel aminocyclitol antibiotics of the general Formula I wherein R 1 , R 3 and R 8 are hydrogen, or one of R 1 , R 3 and R 8 is H 2 NCH 2 (CH 2 ) n CHOHCO-, wherein n is 0 or 1, and the others are hydrogen; R 2 is H or OH; R 5 is hydrogen, hydroxy or halogen, except that when R 2 is hydrogen, R 5 is not hydroxy cis to the amino groups at the 1- and 3- positions; and R 6 and R 7 are each hydrogen or methyl, and acid addition salts thereof are prepared (a) when R 1 ,R 4 and R 8 are each hydrogen, by culturing a nutrient medium containing carbohydrates, a source of assimilable nitrogen, essential salts and a corresponding aminocyclitol of the general formula wherein R 1 , R 2 , R 3 and R 5 are as defined above, except that R 1 and R 3 may also form a single bond between the nitrogen atoms to which they are attached, in the presence of Micromonospora purpurea ATCC 31,119, and isolating the desired product from the medium; (b) when R 1 , R 3 and R 8 are each hydrogen and R 5 is as defined above with the exception of halogen, by culturing a nutrient medium containing carbohydrates, a source of assimilable nitrogen, essential salts and a cyclitol of the general formula wherein R is hydrogen or acetyl, R1 3 is oxo or hydroxy and R1 2 and R1 5 are each hydrogen or OR, in the presence of Micromonospora purpurea ATCC 31,164; (c) when R 1 , R 3 and R 8 are each hydrogen and R 5 is as defined above with the exception of halogen, by culturing a nutrient medium containing carbohydrates, a source of assimilable nitrogen, essential salts and an aminoclitol of the general formula wherein R1 2 and R1 5 correspond to R 2 and R 5 and R1 1 is amino or hydroxy, in the presence of Micromonospora purpurea 31,164; and (d) when one of R 1 , R 3 and R 8 is by reacting the product of (a), (b) or (c) with an N-hydroxysuccinimide ester of the general formula followed by hydrogenolysis of the resulting N- benzylorycarbonyl derivative with hydrogen and a catalyst; followed optionally by salification of the product. dl-Deoxyinosose is prepared by microbiological oxidation of dl-viboquercitol with Acetobacter suboxydans. dl - 2,3,4,6 - Tetrahydroxy - cyclohexanone- (2,4,6-cis) is prepared by reducing dl-epiinosose with hydrogen and PtO 2 and oxidizing the resulting di-epi-quercitol with Acetobacter suboxydans, 2,4,5-Tri-hydroxycyclohexanone(2,4-cis) is prepared by treating 4-cyclohexene-1α,2#-diol with 3-chloroperbenzoic acid and heating the resulting 4,5-epoxycyclohexane-1α,2#-diol with BF 3 etherate. 2,5-Dideoxy-5-iodostreptamine is prepared by treating 2-deoxy-1,6 : 3,4-dicarbonylstreptamine with methanesulphonyl chloride, treating the resulting 5-O-methanesulphonyl derivative with Na1, refluxing the resulting 5-deoxy- 5-iodo derivative with HCl, treating the resulting 2,5-dideoxy-5-iodostreptamine dihydrochloride with acetic anhydride and sodium acetate and hydrolysing the resulting N,N1-diacetyl-2,5- dideoxy-5-iodo-streptamine with aqueous HCl. 2,5-Dideoxy-5-fluorostreptamine is prepared by heating 2-deoxy-5-O-methanesulphonyl-1,6 : 3,4-dicarbonylstreptamine with HCl, reacting the resulting 2-deoxy-5-O-methanesulphonylstreptamine dihydrochloride with aqueous NaOH and then benzyl chloroformate, treating the resulting N,N1- di - carbobenzoxy - 2 -deoxy - 5-O- methanesulphonylstreptamine with KF and hydrolysing the resulting N,N1-dicarbobenzoxy- 2,5-dideoxy-5-fluorostreptamine with aqueous mineral acid. Pharmaceutical compositions having antibacterial activity comprise, as active ingredient, an aminocyclitol antibiotic (I) or an acid addition salt thereof, together with a pharmaceutical carrier.

Claims (1)

PATENT REQUIREMENTS A process for the preparation of an aminocyclitol of the formula I: wherein R 2 and each represents hydrogen or hydroxy; and in the presence of Micromonospora purpurea ATCC 31 164, that if desired an obtained compound is reacted with an N-hydroxysuccinimide ester of formula IV: CH 2 O-C-NRCH 2 (CH 2) n CHOHCO-0-O wherein R 1, R 3 and R 8 each represent : r and R 2 and R 5 each represent vate or hydroxy, R 6 and R 7 each represent vate or methyl, characterized in that a nutrient medium containing carbohydrates, a cold father assimilable nitrogen, essential salts and an aminocyclitol of formula Ha or IIb: van den zero or 1, and that the benzyloxycarbonyl group in the product obtained is subjected to hydrogenolysis with a catalyst for the preparation of a compound, one of R1. R 3 and 128 represent a ta-amino-OC-hydroxy-lower alkanoyl group, and if so beckon a residue-free base is transferred to an acid addition salt thereof.