Recent advances in the synthesis of aminoglycoside antibiotics

Abstract

Abstract-Aminoglycoside antibiotics have established an important position in medicine and synthetic chemistry in this field has recently been developed. A review is provided of general synthetic schemes which we have developed for the total synthesis of streptomycin, dihydrostreptomycin, kanamycins, butirosin B, neomycin C, and others. Resistent bacteria are a serious subject in present chemotherapy and, the mechanisms of resistance have recently been revealed by medical microbiologists. ln the light of these mechanisms, an effort has been made to synthesise compounds, active against resistent bqcteria, by extension of the above mentioned synthetic schemes and by derivation from natural antibiotics.

Aminoglycoside Antibiotics

“…The example below will help to illuminate the problems that must be overcome, but for simplicity and brevity, a significant amount of detail that can be found in the original reviews is omitted (Umezawa, 1974(Umezawa, , 1978(Umezawa, , 1979. Any simple carbohydrate, such as a monosaccharide like glucose, has several hydroxyl groups that must be differentiated in order to react specifically at any particular position; this is normally achieved by a selective protection strategy, in which the relatively close spatial arrangement of particular hydroxyl groups is exploited to protect those groups, leaving others as the free OH groups.…”

Synthesis of (2R,3S,22R,23R)- and (2R,3S,22S,23S)-2,3,22,23-tetrahydroxy-B-homo-8-oxa-5.alpha.-ergostan-7-ones, two new brassinolide analogs

“…Syntheses of brassinolide (la), dolicholide (2a), and many brassinolide analogues (Chart I) have already been reported by different laboratories. 10"25 Structure-activity (1) Grove, M. D.; Spencer, G. F.; Rohwedder, W. K.; Mandava, N. B.; Worley, J. F.; Warthen, J. D.; Steffens, G. L; Flippen-Anderson, J. L.; Cook, J. C. Nature (London) 1979, 281, 216.…”

Synthesis of Aminocyclitol Antibiotics

“…Acetylation of the afore mentioned protected neamine (D) gave L, which, on decyclohexylidenation with aqueous acetic acid, gave M. Treatment of this compound with sodium hydride in dimethylformamide provided a cyclic carbamate (Ν), which has a single free hydroxyl group at C-5 of the deoxystreptamine portion. This intermediate is useful for the regioselective synthesis of 5-0-glycosides, and ribostamycin, butirosin B, and neomycin C have been synthesized by use of this intermediate in our laboratory (24). In regard to the protection of neamine, Kumar and Remers (25) have recently reported other derivatives useful for regioselective syntheses of ribostamycin and butirosin B.…”