Allosamidin allosamizoline

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...

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

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... 

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. 

Achilles tendon collagen [(25, 35 )-3-hydroxyproline], 31 actinomycete (allosamidin), 285 actinomycete (staurosporine), 395 actinomycete A82516 (allosamidin), 285 actinomycete A82516 (allosamizoline), 285... 

The aminocyclitols allosamizoline (266) and demelhylallosamizoline (267), which are found in the pseudotrisaccharide chitanase inhibitors known as allosamidin and demethylallosamidin, have been prepared from cyclic thiocarbamate411 (264) and /1-hydroxy thiourea412 (265) precursors,... 

The chitinase inhibitor allosamidine is a trisaccharide analogue with two N-acetylallosamine units bonded to a highly functionalized cyclopentano-oxazoline unit - allosamizoline. Analogues have now been described with one JV-acetylallo-samine unit, with the disaccharide bonded to an alternative hydroxyl of the cyclopentane, and thirdly with the oxazoline ring inverted. ... 

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 synthesis of the insecticidal compound allosamidine (plus isomer) and aglycone allosamizoline has been reported. The key step in the formation of the allosamizoline involved the oxyamination of cyclopentene 71 with osmium tetroxide and sodio ethyl A -chlorocarbonate in the presence of mercury(U) trifluoroacetate to afford 72 together with regioisomers. See also Chapter 19 for other syntheses of allosamizoline. 

A total synthesis of ( )-allosamizoline from a symmetrical trisubstituted cyclopentene has been reported, and a synthesis of allosamidin and its (1- 3) linked isomer includes a review of the preparation of the starting aminocyclitol and disaccharide moieties. The synthesis of allosamizoline and allosamidin and isomers is also mentioned in Chapters 3 and 18. 

A preliminary report has appeared on the synthesis of allosamizoline, the aglycone of allosamidine (See also Chapter 19, for a full account) as well as the synthesis of the aminooxazoline from the known Helv. Chim. Acta., 1979, 62, 1990) 2R,3S,4R-4-... 

A total synthesis of allosamidin is mentioned in Chapter 3. Full details of the synthesis of allosamizoline, the aglycone of allosamidin, have been reported. Studies of allosamidin biosynthesis using labelled D-glucose and D-glucosamine indicate that the latter sugar is the precursor to each N-acetyl-o-allosamine and to the allosamizoline component. ... 

Allosamidin (21, Figure 3) was identified as a selective and powerful chitinase inhibitor in 1987 [13]. As such, it generated interest as a potential insecticide and fungicide. Allosamidin is composed of a 3,3 -epf-chitobiose (3-linked to a novel aglycone sector termed allosamizoline [14]. This unique structure is believed to impart to it the function of a transition-state mimic for the hydrolysis of chitin [15]. The possibility that the electrophilic nature of the oxazoline linkage could allow it... 

Allosamidin has been converted to its demethyl and didemethyl analogues by treatment with methylamine and ammonia respectively, and 6- and 6"-0-acyl derivatives were also prepared. A study of the biosynthesis of allosamidin suggests that one A -methyl group is introduced before cyclization of the oxazoline ring. A synthesis of the cyclopentane-based (-)-allosamizoline moiety of allosamidin is mentioned in Chapter 18. 

The preparation of an allyl intermediate from iodooxa-zoline 95 en route to (—)-allosamizoline was achieved though a substrate-controlled diastereoselective Keck allyl addition to give 96 (Scheme 25.45). Allosamizoline is the aglycon of allosamidin, which was isolated from mycelial extracts of Streptomyces sp. No 1731 and inhibits all characterized family 18 chitinases. 

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