Synthesis of biologically active iminosugars using unconventional methods - microwave and ultrasonic irradiation
Iminosugars are the most attractive class of carbohydrate mimetics. They show powerful inhibition and modulation of carbohydrate processing enzymes, alterations which are implicated in a wide variety of diseases. Iminosugars, initially known as potent glycosidase inhibitors, have also been found to be inhibitors of glycosyl transferases, glycogen phosphorylase, nucleoside processing enzymes, metalloproteinases, etc. widening the area of their medical applications.
To date over 100 compounds have been isolated from natural sources, most of them from plants and only a limited number from bacteria or fungi.
Structurally, iminosugars can be classified according to the size of the ring (pyrrolidine, piperidine, azepane or bicyclic), the type of substituents (typically hydroxy groups, but also carboxylic acids and amides are found in nature) and the stereochemistry of their chiral centers.
The main approach to synthesis adopts carbohydrates or other chirons as starting materials, introducing the endocyclic nitrogen through synthetic manipulations. Such routes are hampered by long synthetic sequences that have lessened their commercial potential. The field is also now beginning to attract further interest for de novo and enzymatic synthesis, which may offer advantages in certain cases.
The polar nature of the molecules coupled with their typical lack of UV chromophores also requires specialized analytical methods to be developed.