Aminoglycoside Structures

Naturally occurring aminoglycosides are amino sugars consisting of an aglycon unit, which can be cyclic or open chain. The aglycon is either streptamine, its related aminocyclitols, cyclitol, monoaminocyclitol, or a noncyclitol moiety. Therefore, these natural products can be divided into three major classes: (1) aminoglycosides containing streptamine and its related aminocyclitols, (2) aminoglycosides containing cyclitol and/or monoaminocyclitol, and (3) aminoglycosides having a noncyclitol moiety in their structures.

A. Aminocyclitol Aminoglycosides Containing Streptamine and Its Derivatives

The aglycon unit in aminocyclitol aminoglycosides that contain streptamine and its derivatives is 2-deoxystreptamine (compounds 1-3 ) 1 (2-DOS), streptamine 2, or streptidine 3.

Most of the aminocyclitol aminoglycosides with high antibacterial activity have the 2-deoxystreptamine as the aglycon unit. The carbon atom bearing the amino group with the R configuration is assigned number 1 in the structure. The most active aminoglycosides are those with their sugar units substituted at positions 4 and 5, or 4 and 6, of the aglycon unit. By convention, the sugar unit attached to the 4-position

Compounds 1-3

of 2-DOS is designated by the primed (') numbers and those attached to the 5- or 6-positions are indicated by the double-primed (") numbers.

1. Aminoglycosides Containing 2-Deoxystreptamine

(a) 4-Substituted 2-Deoxystreptamine. Among 4-substituted-2-deoxystreptamine aminoglycosides, three pseudotrisaccharides, apramycin, oxyapramycin (14) [26], and saccharocin (15) (compounds 13-15 ) [27,28], show more potency than neamine (4) and are active against many resistant bacterial strains. Members of this group of pseudodisaccharides (compounds 4-12 ) are minor metabolites of Actinomycetes and show weak antibacterial activity [29-35].

(b) 5-Substituted 2-Deoxystreptamine. These aminoglycoside antibiotics have an unusual spiro ring junction in their structures. They show weak antibacterial activity rr<

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