Mannojirimycin

Microbiological oxidation of mannojirimycin with Gluconobacter suboxydans I AM 1829 gave D-mannono-S-lactam (3). It exhibited powerful inhibition of rat a-mannosidase and of apricot (3-glucosidase. The structures of 2 and 3 were determined on the basis of NMR spectroscopy and X-ray structural analysis.  

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A. Amone, P. Bravo, A. Donadelli, and G. Resnati, Fluorinated analogues of nojirimycin and mannojirimycin from a non-carbohydrate precursor, Tetrahedron, 52 (1996) 131-142. 

The simple piperidine pelletierine from Punica granatum (pomegranate) (Punicaceae) and Duboisia myoporoides (Solanaceae) is an anthelmintic. The simple piperidine derivatives deoxy-mannojirimycin (DMJ) and deoxynojirimycin (DNJ) from Lonchocarpus species (Fabaceae) are glycosidase inhibitors because they are structurally similar to the pyranose (six-membered ring) sugar moieties of the glycosidase disaccharide substrates. 

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...

Scheme 10. Biosynthetic formation of 1-deoxynojirimycin (18) and mannojirimycin (19). Note the inversion of the label (the 1 -label becomes a 6-label), i. e., the 5-deoxygenation is really a 2-deoxygenation...

Excellent examples for chiral pool access to various iminoalditols via Approach C were provided, for example, by Lundt and coworkers (Scheme 9.12) [170]. Additionally, an interesting chlorobenzene-based de novo access to mannojirimycin was reported by Hudlicky and his group (Scheme 9.13) [171]. 

Ding, Y, Hindsgaul, O, Syntheses of l-deoxy-3-5 -(l-thio-a-D-glucopyranosyl)-mannojirimycin and l-deoxy-3-0-(5-thio-a-D-glucopyranosyl)-mannojirimycin as potential inhibitors of endo-a-D-mannosidase, Bioorg. Med Chem. Lett., 8, 1215-1220, 1998. 

Hudlicky, T, Rouden, J, Luna, H, Allen, S, Microbial oxidation of aromatics in enantiocontrolled synthesis. 2. Rational design of aza sugars (emio-nitrogenous). Total synthesis of (-l-)-kifunensine, mannojirimycin, and other glycosidase inhibitors, J. Am. Chem. Soc., 116, 5099-5107, 1994. 

Dondoni, A, Merino, P, Perrone, D, Totally chemical synthesis of azasugars via thiazole intermediates. Stereodivergent routes to (—)-nojirimycin, (—)-mannojirimycin and their 3-deoxy derivatives from serine. Tetrahedron, 49, 2939-2956, 1993. 

Nojirimycin B (248, mannojirimycin) was isolated from the culture broth of Streptomyces lavendulae, along with nojirimycin [550]. The structure of 248 was established by NMR and by its oxidation to mannonic-6-lactam. Nojirimycin B was a potent inhibitor of apricot emulsin and rat epididymal a-mannosidase, but was less active against Trichoderma viride p-glucosidase. It was weakly active against Xanthomonas oryzae, but inactive against other bacteria [550]. 

Yokoyama et al. reported that the palladium-catalyzed cyclization of the carbamate 186 gave the piperidine 187, which was converted to 1-deoxy-mannojirimycin 188, with excellent diastereoselec-tivity (Scheme 62).133... 

Mannojirimycin (1) and 1-deoxymannojirimycin (2) were prepared from 2,3 5,6-di-0-isopropylidene-a-D-mannofuranose (26) (Scheme 5). The oxime 27, prepared from 26, underwent reduction by hydrogenation in the presence of Raney nickel, and subsequent removal of the trityl group afforded the amines 28 and 29. Acid hydrolysis of 28 afforded 30 (21%), which was converted to 31 (28%) that upon treatment with Dowex 1 (OH ) resin afforded 1. On the other hand, hydrogenation of 28 gave 32, which upon removal of the... 

D-Gulonolactone was similarly converted into 1-deoxy-L-mannojirimycin (57) and L-mannonolactam (58) in an overall yield 20 and 24%, respectively, from D-gulonolactone. 

Synthesis from o-mannose Syntheses of a-homonojirimycin (1), 6-cp/-a-homo-mannojirimycin (39) and the pipecolic acid derivative 36 from D-mannose have been reported (Scheme 5). The azidolactone 31, ° prepared from diacetone mannose (30), nnderwent selective removal of the terminal isopropylidene gronp, followed by selective protection of the resnlting primary hydroxyl gronp with fcrt-butyldimethylsilyl chloride to... 

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