Hydroxylated indolizidines

Although more rare, the ring opening of A-acyl (3-lactams has also been realized by using hydrides, giving rise to the corresponding reduction products. In this context, Scheme 40, Lee and Pak [107] have described the treatment of A-Boc (3-lactam 119 with lithium aluminium hydride to give A-protected amino alcohol 120. Compound 120 could serve as potential intermediate for the synthesis of various hydroxylated indolizidine alkaloids. 

Swainsonine, the enantiomer of the naturally occurring swainsonine, was enantiospecifically synthesised and proved to be a very potent inhibitor of naranginase, a (+)-ramannosidase, while (-)-swainsonine does not inhibit the same enzyme. Some other more highly hydroxylated indolizidines were also synthesised but proved to be less efficient as glycosidase inhibitors [113]. 

A USDA group was struck by the similarity in structure between the two hydroxylated indolizidines 95 and 96, and was led to examine the effect of castanospermine on hydrolytic enzymes. The American workers found it was a powerful inhibitor of both a- and [3-glucosidases [1151 it was further shown to inhibit glycoprotein processing [116], which in... 

There are no known naturally occurring pentahydroxyindolizidines, although several have been synthesized. Uniflorines A and B from Eugenia uniflora ere. originally formulated as 1,2,6,7,8-pentahydroxyindolizidine (41) and the structurally improbable 5-hydroxylated indolizidine (43), respectively, but these have now been shown to be the polyhydroxypyrrolizidines, 6-f/ /-casuarine and casuarine (39). 

Alternatively, the diastereomeric mixture of aldol adducts undergoes lithium aluminum hydride reduction, primary alcohol silylation, and chromatographic separation to afford 291. Subsequent Mitsunobu inversion at C-3 to furnish the j -alcohol 292 followed by a depro-tective sequence and ring closure provides (+ )-castanospermine (293). This poly-hydroxylated indolizidine alkaloid isolated from Castanospermum australe and Alexa leipetala is a potent inhibitor of various a- and j8-glucosidases [98] (Scheme 68). 

D. Streptomyces Metabolites A58365A and A58365B Hydroxylated Indolizidine Alkaloids... 

Rao and coworkers have reported formal syntheses of (—)-2-ep -lentigi-nosine (128) and several other hydroxylated indolizidines from the D-ribose derivative 166 (Scheme 21). This precursor was converted by treatment... 

A potentially general route to unusual hydroxylated indolizidines, e.g. 158 (sugar numbering shown), has been developed using L-arabinose, and nitrone 159 (from either D- or L-arabinose) has been applied to the synthesis of racemic hydroxylated p)OToIizidines and indolizidines. ... 

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