Influence of Multiple & Cooper ative Hyd rogen Bon ding on the Acidity of Polyhydro xylated Piperidines : Electron Density T opologic al Analysis

Iminosugars (“aza sugars”) are structural a nalogues of sugars in w hich the ring oxygen atom is replaced by a nit rogen atom. In recent y ears, there has been much interest in synthetic and naturally occurring iminosug ars. The biological prop erties of iminosugars arise because they interfe re with the function of carbohydrate processing enzymes. Naturaly occurring sugars mimics with a nitrogen atom in the ring are classified into five st ructural classes: polyh ydroxylated piperidines , pyrrolidi nes, indolizidines, pyrrolizidines, and nortop anes. Polyhydroxylated piperidines (“azasugars”) have rec eived a great deal of attention recently. These alkaloidal sugar mimics contain the same dense stereochemical information a s the common hexoses, and many of them exh ibit potent biological activity. Also , azasugars have been p ostulated a s possible th erapeutics including th e treatment of viral infections,۶ diabetes,۷ and cancers,۸ and as invaluable tools in the study of enzyme mechanism. ۹ The inter esting behavior of intra molecular h ydrogen bon ds both from the practical and theoretical poi nts of view have receive d increased attention in recent years. This can be attribute d to the fact that the va lue of hydrogen bond energy is only a few kilocalories per mole an d can be r eadily perturbed by any change in its environ ment. Although, hydro gen bonding interaction s are usually weaker th an classical chemical bonds, they play an important role in chemical and physic al propertie s in both intramolecular and inter molecular interactions. The capacity of organi c molecules to form hydrogen bo nds affects very significantly a wide range of their physic al properties and is thu s directly linked to man y important properties, including aqueous solubility, boiling, and me lting points, viscosity , solvatoc hromism, and lipophilicity. Furthe rmore, acid-base reacti ons are ubiquitous in nat ure and pla y a critical role in a myriad of chemical transfor mations. Hydrogen bo nds are se rved as templates for proton tr ansfer reacti ons and organizationof three-di mensional structures of O-H and N-H conta ining comp ounds. They also lead t o an easier gas-phase d eprotonation of alcohols . In our previous work [۱] we mea sured gas-ph ase acidity and pKa of a series of polyols in dimethyl sulfoxide and o ur results in dicate that m ultiple hydrogen bonds to a single charged center lead to greatly enhanced acidities .

کلیدواژه ها:

Polyh ydroxylate d piperidines ، Hydrogen bonding ، Gas-phase acidity ، pKa ، Dimethyl sulfoxide.