Amylostatins

Several mono-carba-oligosaccharidic alpha amylase inhibitors, such as acarbose and its homologs, amylostatins, trestatins, oligostatins, adipo-sins, and so on, have been isolated from cultures of micro-organisms, and considerable interest in the biochemistry and chemistry of this class of inhibitors has been stimulated. The characteristic core-structure for inhibitory action is composed of a trihydroxy(hydroxymethyl)cyclohexene moiety and a 4-amino-4,6-dideoxy-D-glucopyranose moiety, bonded by way of an imino linkage at the allylic position. A similar structural unit has been found in the antibiotic validamycins. 

The first synthesis, by method a, of amylostatin (XG) was reported by Kuzuhara and Sakairi. The synthon for the cyclohexene moiety was the benzylated allyl bromide 382, derived from D-glucose by the sequence 378 — 382 of the Perrier reaction. The coupling reaction of 382 using an excess of 4-amino-T,6 -anhydro-4,6-dideoxymaltose tetrabenzyl ether (383), and sodium iodide in DMF for 3 days produced a mixture of the epimeric monocarba-trisaccharide derivatives, separation of which gave the protected derivatives in 15% yield. 

An alternative synthesis,by method h, was conducted by coupling 357 and 1,6-anhydro-4-0-(3,4-anhydro-6-deoxy-a-D-galactopyranosyl)-a-D-glucopyranose (392a) in 2-propanol at 120° this yielded a diastereoiso-meric mixture, from which, after the usual treatment, amylostatin (XG) was isolated in 20% yield. 

There are also small peptide inhibitors of a-amylase found in certain Streptomyces (29). Two carbohydrate a-amylase inhibitors, Acarbose and Amylostatin, have been described (30-32). Their structures are shown in Figure 3. The inhibitors are very similar in structure. 

A further structural type of G. i. are the pseudooligosaccharides. These include as a-glucosidase inhibitors the amylostatins (e.g., acarbose), adiposins, oligo-statins, and trestatins. 

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