Trehalase inhibitors analogues

POTENTIAL TREHALASE INHIBITORS SYNTHESES OF TREHAZOLIN AND ITS ANALOGUES... 

The carbocyclic analogue of the trehalase inhibitor, trehazolin, has been prepared and reported to have potency indistinguishable from the natural product." The synthesis of other antibiotic-related cyclopentane derivatives such as analogues of mannostatin A, allosamidin (and allosamizolin) and a 4-membered carbocyclic thiazole analogue of oxetanocin, are covered in Chapter 19. 

A series of complex polyhydroxylated cyclamino acids 15-19 have been prepared by Fleet s group as analogues of the potent trehalase inhibitor, trehazolin 14. A central feature of this chemistry was the use of either an azide- or fluoride-mediated intramolecular aldol reaction of the carbohydrate-derived lactones carrying a 2-azido (ot 2-iodo) substituent as illustrated in Scheme 4. 

Richardson s interest in these trehalose epoxides stemmed from his desire to prepare a wide range of modified trehalose analogues for evaluation as inhibitors of the trehalase of insects, as trehalose is known to be the storage carbohydrate of many insects and good inhibitors of this processing enzyme could potentially function as green insecticides. 

In the early days of this Advances series, authors were offered the opportunity to record experimental procedures as part of their contributions, but this has been rarely used in recent years. However, the practice is revived here in the article by El Nemr and El Ashry (Alexandria) on the synthesis of trehazolin, a natural nitrogen-containing pseudodisaccharide that is an inhibitor of the enzyme trehalase, together with various analogues. These synthetic targets can be approached in a wide variety of ways, and the authors present for each synthetic sequence sufficient detail to permit an experienced synthetic chemist to repeat the procedure. 

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