Abstract
A new class of aminocyclitol derivatives with the bicyclo[4.2.0]octane skeleton was synthesized starting from cyclooctatetraene. Photooxygenation of trans-7,8-diacetoxy- and cis-7,8-dichlorobicyclo[4.2.0]octa-2,4-diene afforded the bicyclic endoperoxides. Reduction of the latter with thiourea followed by a Pd(0) catalyzed ionization/cyclization reaction gave the corresponding oxazolidinone derivatives. Oxidation of the double bond with KMnO4 or OsO4 followed by acetylation gave the acetate derivatives, the exact configuration of which was determined by spectroscopic methods. Hydrolysis of the oxazolidinone rings and removal of the acetate groups furnished the desired aminocyclitols.
Highlights
Among the myriad of naturally occurring compounds are the aminocyclitol-containing natural products, which represent a large family of sugar derived microbial secondary metabolites and include the clinically active aminoglycoside inhibitors [1,2,3,4,5,6,7,8,9,10,11], many of which are widely used for the treatment of diseases in humans, animals and plants [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
Antibiotics containing an aminocyclitol unit have stimulated the development of synthetic methodologies [16] in the search for analogues with enhanced pharmacological profiles [6]
Diacetoxydiene 9 was synthesized in 99% yield from cyclooctatetraene (8) by the addition of mercury(II) acetate [31]
Summary
Among the myriad of naturally occurring compounds are the aminocyclitol-containing natural products, which represent a large family of sugar derived microbial secondary metabolites and include the clinically active aminoglycoside inhibitors [1,2,3,4,5,6,7,8,9,10,11], many of which are widely used for the treatment of diseases in humans, animals and plants [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15].the design of carbohydrate mimetics, which can be potent inhibitors of glycosidase (1–4) [11,12,13,14,15,16], we have developed a method for rapid entry to these compounds.Glycosidase and related enzymes are involved in the biosynthesis of the oligosaccharide chains [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Trost et al [23,24] have reported a regio- and stereoselective Pd(0) catalyzed reaction of diols in the presence of p-toluenesulfonyl isocyanate for the introduction of the amino alcohol functionality. As a part of our program directed towards the synthesis of potential glycosidase inhibitors we used a bicyclo[4.2.0]octane framework for OH, chlorine and NH2 groups as an intriguing carbohydrate alternative [26,27,28,29,30]. We report the synthesis of the new aminocyclitol analogues 6 and 7 from cyclooctatetraene.
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