Allosamidin

Allosamidin (2) and its congeners demethylallosamidin (3), methylallosamidin (4), methyl A-demethylallosamidin (5), glucoallosamidin A (6) and glucoallosamidin B (7) are the first examples of endochitinase inhibitors. They were isolated from the mycelial extract of Streptomyces sp. 1713 and related actinomycete SA-684 and A82516. They exhibit the inhibitory activity against the chitinases of the silkworm Bombyx mori in vitro and prevent its larval ecdysis in It has been thought that the chitinase inhibitor would 

Allosamidin (2) has a unique pseudotrisaccharide structure consisting of two N-acetyl-D-allosamine units and a novel five-membered aminocyclitol, named allosamizoline (8). This is the first example, in nature, having allosamine derivatives. The relative configuration of 8 was initially suggested to have a 3,4-cw diol configuration and later it was revised 

6-aldehyde glucosamine derivative or their enol equivalents, which would undergo an aldol condensation of C-5 with C-1. 

Many syntheses of allosamizoline and its analogues from noncarbohydrate have been reported. Carbohydrates have been also used for the synthesis of allosamizoline, which upon suitable protection to be a glycosyl acceptor that can be coupled with the required oligosaccharide donor would led to the total synthesis of allosamidin. 

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Gooday, G.W., Brydon, L.J. and Chappel, L.H. (1988) Chitinase in female Onchocerca gibsoni and its inhibition by allosamidin. Molecular and Biochemical Parasitology 29, 223-225. 

The diversity of chitinases is also evident in their different responses to the antibiotic allosamidin. This is a specific inhibitor of invertebrate, vertebrate, fungal and bacterial chitinases, but does not inhibit the plant chitinase from yam (34-37), Of the invertebrate chitinases reported, activity from a nematode was exquisitely sensitive, with that from an insect a thousand-fold less so a chitinase from turbot fish plasma was a thousand-fold more sensitive than one from the fish stomach. 

Kassab, D. J. Ganem, B., (1999) An enantioselective synthesis of (-)-Allosamidin by asymmetric desymmetrization of a highly functionalized meso-epoxide. J. Org. Chem., 64 1782-1783. 

Since the isolation of the chitinase inhibitor allosamidin from Streptomyces [90], the aminohydroxy-substituted cyclopentanes have been recognized as powerful and specific inhibitors of glycosidases [91]. The synthesis of (+) [92], as well as of racemic [93] mannostatin, which is a strong mannosidase inhibitor, should be mentioned here (Fig. 1). 

In 1986 the novel chitinase inhibitor (—)-allosamidin was discovered in fermentation broths of Streptomyces sp. 1713 by Sakuda and coworkers.1 (—)-Allosamidin is unusual inasmuch as it contains two N-acetyl-D-allosamine residues glycosidically linked P-1,4 to one another. In turn, this disaccharide is connected to a cyclopentanoid known as (—)-allosamizoline in the manner shown in Figure 11.1. 

Scheme 9. 5-Deoxysugars The 5-amino-5-deoxysugars (piperidinoses) nojirimycin (17), 1-de-oxynojirimycin (18), mannojirimycin (19) and galactostatin (20). The tetrahydropyrrol moiety of bulgecin A (21) and the allosamizoline unit 22 of allosamidine (23can also be considered as 5-deoxysugars. The derivation of 22 from the pool has already been proven...

Nakata, M, Akazawa, S, Kitamura, S, Tatsuta, K, Enantiospecific total synthesis of (—)allosazoline, an aminocyclitol moiety of the insect chitinase inhibitor allosamidin. Tetrahedron Lett., 32, 5363-5366, 1991. 

Carbasugars Cyclitols Glycosidase inhibitors Cyclophelitol Allosamidin Trehazolin Neuraminidase inhibitor Tamiflu Intramolecular [3+2] cycloaddition The Ferrier reaction... 

Allosamizoline The Aglycone of the Chitinase-Specific Glycosidase Inhibitor, Allosamidin... 

A. Berecibar, C. Grandjean, and A. Siriwardena, Synthesis and biological activity of natural aminocyclopentitol glycosidase inhibitors Mannostatin, trehazohn, allosamidins and their analogues, Chem. Rev., 99 (1999) 779-844. 

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