Mannostatins

Base-catalyzed nitromethane cyclization of the dialdehyde generated by periodate oxidation of 1,2-O-cyclohexylidene-myo-inositol affords the nitrodiol with 1,4/2,3,5-configuration. This is converted into the a-mannosidase inhibitor, mannostatin A (Eq. 3.60).98... 

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). 

An asymmetric Diels-Alder reaction of a chiral nitroso dienophile has been employed by Ganem et al. in order to open an elegant access to enantiomerical-ly pure (-t-)-mannostatin A 7-57 and several derivatives thereof [519], The cycloaddition of the heterodienophile 7-54 derived from mandelic acid to 1-me-thylthiocyclopentadiene 7-55 proceeded only in moderate diastereoselectivity, however, the desired product 7-56 was easily separated from its diastereomer. 

Naturally occurring cyclopentylamines are found in aUosamidin, mannostatin and trehazolin, aU of which can be regarded as sugar mimics, exhibiting inhibitory activities toward glycosidases [333]. 

Enol lactones have been used to construct cyclopentenones [341], which have been used to prepare mannostatin A [342]. More recently, a related strategy was applied to the synthesis of trehazolin analogs [343]. 

Li, C, Fuchs, P L, Methanesulfenyl triflate promoted iminosulfenylation of an allylic trichloroacetimidate. An efficient and stereospecific total synthesis of (-I-) mannostatin A, Tetrahedron Lett., 35, 5121-5124, 1994. 

Mannostatin A, a pentasubsthuted amino-cyclopentane produced by Streptoverticillium verticillus var quintum ME3-AG3 [113], is also a specific inhibitor of a-D-mannosidase and has shown anti-metastatic activity [114],... 

Irradiation of pyridinium perchlorate in dilute perchloric acid (Xirr = 254 nm) is reported to give an amino diol which can be acetylated to the corresponding amido-diacetate (186 R = Ac), and which itself can be converted into the a-mannosidase inhibitor (+)-mannostatin A (187). The photochemical rearrangement of 1-acetyl-l,2-dihydroquinoline-2-carbonitriles to 3,1-benzoxazines and cycloprop[b]indoles has been described, and photo-... 

Aziridines are important intermediates in the photochemical reactions of pyridinium salts. Thus irradiation of salts (135) in the presence of a nucleophile (nuc) affords the aziridine (136) that readily undergoes ring opening to yield the aminocyclopentane derivatives (137). The reaction can be applied to the synthesis of (+)-mannostatin A (138) starting from pyridinium perchlorate. Other examples of the synthesis of such aminocyclopentitols have been reported by Acar et al For example, the irradiation of (139) affords the substituted aziridines (140) in moderate to excellent yields. Further reactions... 

Y. Nishimura, Y. Umezawa, H. Adachi, S. Kondo, and T. Takeuchi, Enantiodivergent synthesis and biological activity of mannostatin analogs, J. Org. Chem., 60 (1996) 480-488. 

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. 

G. Hu, M. Zimmermann, C. V. Ramana, and A. Vasella, Cyclopentanes from N-amino-gluconolactams S. A synthesis of mannostatin A, Chem. Commun., (2003) 952-953. 

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