A-Mannosidase inhibitor

Colgate, S. M., Dorling, P. R. and Huxtable, C. R. 1979. A spectroscopic investigation of swainsonine an a-mannosidase inhibitor isolated from Swainsona canescens. Austral. J. Chem. 32 2257-2264. 

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... 

G. W. J. Fleet, P. W. Smith, S. V. Evans, and L. E. Fellows, Design synthesis and preliminary evaluation of a potent a-mannosidase inhibitor l,4-Dideoxy-l,4-imino-D-mannitol, J. Chem. Soc., Chem. Commun. (1984) 1240-1241. 

G. Limberg, I. Lundt, and J. Zavilla, Deoxyiminoalditols from aldonic acids. VI. Preparation of the four stereoisomeric 4-amino-3-hydroxypyrrolidines from bromodeoxytetronic acids. Discovery of a new a-mannosidase inhibitor, Synthesis (1999) 178-183. 

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-... 

Esters of swainsonine appear to offer therapeutic advantages in terms of specificity for Golgi a-mannosidase II, improved pharmacokinetics, and diminished side effects (143). Although 2- and 8-acyloxy esters of swainsonine were two to three orders of magnitude less active as a-mannosidase inhibitors in vitro than the parent alkaloid, the 2-butanoyl, 2-octanoyl, and 2-p-nitrobenzoyl esters, which are soluble enough to enter viable tumor cells, were as effective as swainsonine in vivo, apparently because they are hydrolyzed to swainsonine with intracellular esterases. These compounds may thus be advantageous as prodrugs. 

The a-mannosidase inhibitors mannostatin A (CsHijNOjS, Mr 179.24, mp. 121 C) and mannostatin B (C H 3N04S, Mr 195.24), isolated from Streptover-ticillium verticillus var. quintum, represent a new structural type. 

CsHisNOj, Mr 179.17. A mannosidase inhibitor isolated, together with deoxymannojirimycin, from cultures of Streptomyces lavendulae. Both compounds exhibit antiviral activity. 

Guanidinium and isothiourea derivatives such as 46 and 47 were also reported that exhibited potent and selective (3-glycosidase inhibitory activity, in contradiction with the previous castanospermine analogues depicted above. Noteworthy, sulfamide-type indolizidines such as 48, in which the thiourea moiety has been replaced by a sulfamide group, were also described and found to be modest a-mannosidase inhibitors... 

The cyclopentane (3), a potent a-mannosidase inhibitor, has been prepared from a previously-known intermediate made by intramolecular nitrone-alkene cycloaddition (see Vol. 13, p. 152) an epimerization at the carbon atom indicated was effected at the aldehyde oxidation level.3... 

Mechanism and Regulation of Protein Turnover Effect of the a-Mannosidase Inhibitor, Swainsonine, on Glycoprotein... 

Using another EH overexpressed in Y. lipolytica (Oxy-10), the kinetic resolution of an epoxyamide was performed at 50% conversion, resulting in the optically pure residual (R,i )-epoxide and the formed threo-diol with )delds of 32% and 22%, respectively [102] (Figure 8.33). The remaining (K,K)-epoxide is of synthetic interest, because it is used for the S5mthesis of the a-mannosidase inhibitor (-)-swainsonine. 

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