R

417 R = COCH2NH2

418 R = COCH2CH(NH2)(CH2)3NH2

Compounds 419-426
Compounds 427-432

as glycosyl donors. However these compounds were devoid of antibacterial activity, indicating that the presence of an ether linkage at the 4'-position (in comparison with apramycin, 48) is probably essential for antibacterial activity in this class of aminoglycoside antibiotics [251].

J. Noncyclitol Aminoglycosides

1. Trehalosamines

Trehalosamine (433), an a,a-(1^1)-linked disaccharide produced by Streptomyces lavendulae, is an aminoglycoside antibiotic composed of d-glucose and 2-amino-2-deoxy-d-glucose [252].

Ogawa and colleagues [253,254] used a racemic inosamine derivative to prepare the trehalosamine analogs 434-436 by glycosylation with an appropriately protected glucopyranosyl bromide. Likewise, a number of pseudosugar analogs, including the a-d-glucosides 437 and 438, were synthesized by glycosylation of the ยก-d-glucopyranose derivative 439 with the a-dl-glucopyranose 440 in the presence of trimethylsilyl trifluoromethanesulfonate (compounds 433-440 ). However, these compounds exhibited no antibacterial activity [37,254].

2. Acarviosins

Acarviosin 441, an a-glycosidase inhibitor, is a maltose-type pseudodisaccharide that can be prepared from methanolysis of acarbose 442 [255]. It has been shown to have five times more inhibitory activity than its precursor acarbose, for which the first total synthesis has been described by Ogawa's group in 1989 [256].

The methylacarviosin 447, a core structure of acarbose and related pseudo-oligosaccharidic a-amylase inhibitors, together with its 6-hydroxy analog 448, were prepared by Shibata et al. [257] from the corresponding oligobiosaminide derivatives 443 and 444. The aziridine intermediates 445 and 446 were treated with hydrochloric acid to give the corresponding 6'-chloro derivative, and then elimination of the chlorine by base furnished the title compounds 447 and 448 as peracetylated derivatives (compounds 441 -448 ).

The same group has also prepared several other a-glucosidase inhibitors, including 1',6'- and 3',6'-anhydro derivatives of acarviosin [258], methylacarviosin

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