Castanospermine-related alkaloids

The bioactivity of castanospermine and related alkaloids continues to inspire chemists to devise new synthetic routes to the alkaloid, as well as to iimumerable structural, stereochemical and other analogs. The ensuing discussion deals only with reported syntheses of the four natural products 239-242. For syntheses of other reported stereoisomers of the indolizidine-l,6,7,8-tetraols (Fig. 4), the following references should be consulted (-)-l-epicastanosp>ermine (243) (194), ( )-7-epicastanospermine (195) and (15,6S, 75, 87f,8a7 )-7-epicastanospermine (244) (196),... 

This method was quite sensitive and selective. The detection limit in aqueous solution was 0.75 ng, and from plant material 2.5 ng of castanospermine could be detected. This method was also found to be suitable for the structurally related alkaloids 1-deoxynojirimycin, 1-deoxymannojirimycin, and swainsonine. 

Christiansen AL, Rasmussen KE, H0iland K (1984) Detection of psilocybin and psilocin in Norwegian species of Pluteus and Conocybe. Planta Med 50 341-343 Donaldson MJ, Broby H, Adlard MW, Bucke C (1990) High pressure liquid chromatography and pulsed amperometric detection of castanospermine and related alkaloids. Phytochem Anal 1 18-21... 

The formation of thiocarbonyl ylids by the reaction of metallocarbenoids with thiocarbonyl compounds has not been extensively studied, as noted by Padwa and Weingarten in a review [167]. However, formation of rings by interaction of these compounds has recently received some attention. A key step in the synthesis of a polyhydroxylated indolizidine alkaloid related to castanospermine is the reaction of diazoketone with a thioamide, in the presence of rhodium acetate [135]. After desulfurisation an enaminone was obtained. 

Taylor, D L, Fellows, L E, Earrar, G H, Nash, R J, Taylor-Robinson, D, Mobberley, M A, Ryder, T A, Jeffries, D J, Tyms, A S, Loss of c3domegalovirus infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis. Antiviral Res., 10, 11-26, 1988. 

Castanospermine s antitumor potential continues to receive attention. Recent in vitro studies have examined inhibition of tyrosinase activity in human melanoma cells (181), effects on intracellular transport of an avian erythroblastosis oncoprotein (277), and consequences for biosynthesis, maturation, and transport of ai-antitrypsin in the human hepatoma HepG2 cell line (257,272). The latter study was the first to show the inability of 239 to permeate the plasma membrane in intact HepG2 cells. In vivo experiments with nude mice proved that the alkaloid altered the glycosylation of endothelial cells, prevented angiogenesis, and inhibited tumor growth (273). However, recent in vivo studies failed to reveal cytotoxicity towards two rat prostate adenocarcinoma cell lines, or effects on cell characteristics related to metastatic potential (274). Uptake and metabolism of the more lipophilic 6-0-butanoylcastanospermine in tumor cell lines and after oral administration to mice was traced with C-labeled material, and showed rapid conversion into the parent alkaloid, which is undoubtedly the active metabolite (275). Multiple dosing in mice produced additive results. 

The plant alkaloid castanospermine 155 and the related piperidine alkaloid 1-deox-ynojirimicin 160, like several other polyhydroxylated octahydroindolizidines, piperidines and pyrrolidines, are potent glycosidase inhibitors. These nitrogen bases are of considerable interest for the study of biosynthetic processes and, in addition, castanospermine and some of its derivatives may be of clinical value as antineo-plastic agents and as drugs in the treatment of AIDS. 

Fellows, L. E., Castanospermine, swainsonine, and related polyhydroxy alkaloids from plants, Phytochem. Soc. North America, Annual Meeting, 1988. 

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