Polyhydroxy piperidines

Fuentes s group reported the synthesis of polyhydroxy piperidines (Scheme 8) starting from partially protected P-D-ribopyranosylenamine 22 [58]. Thus, mesylation on the free hydroxyl group led to the corresponding 5-mesyloxy and 5-chloro derivatives 23 and 24, the latter obtained by nucleophylic substitution on the mesyloxy group when longer reaction times and more concentrated solutions were used. 

Polyketide Alkaloid Phytotoxins Polyhydroxy Piperidine Alkaloids References... 

Aspidiaceae (Fellows et al., 1986 Janzen et al., 1990). These compounds are similar in some regards to coniine (48), a nonhydroxylated piperidine alkaloid. In some legumes, polyhydroxy piperidine alkaloids make up as much as 2% of the dry weight of the plant. These compounds are similar structurally to sugars and are potent inhibitors of glycosidase activity. Specificity varies and some compounds of this series inhibit mannosidases, others fucosidases, and so forth. No glucosidase inhibitor has been reported to present (Fellows et al., 1986) (also see Chapter 15). 

The products presented in scheme 5 show that it should be possible by subsequent introduction of amino groups through halogen or oxirane functionalities, to get an efficient entry into a series of polyhydroxylated piperidines (azasugars) [6,7,30] by intramolecular reductive amination. This class of compounds gained much interest recently because of its biological activity as potential glycosidase inhibitors [31-33]. In scheme 8 novel substitution patterns of polyhydroxy piperidines (boxed), which we synthesized stereoselectively by our own new procedures [34], are compared with known compounds derived from natural sources. 

In recent years, representatives of 3 new classes of alkaloid have been isolated from both plants and micro-organisms, namely polyhydroxy derivatives of indolizidine, pyrrolidine and piperidine. 

The monocyclic members of the polyhydroxy alkaloid group possess either five- or six-membered ring systems with a heterocyclic secondary nitrogen atom and fall into the pyrrolidine and piperidine classes, respectively. They have structural affinities to aminosugars and therefore are often referred to as iminosugars. 

The fhiits, leaves, and root bark of white mulberry trees Morus alba-, Moraceae) have yielded many polyhydroxy pyrrolidines and piperidines,especially DNJ and its glycosides. One unusual alkaloid is the Ai-propionamide derivative of (2if,3if,4if)-2-hydroxymethyl-3,4-dihydroxypyrrolidine (13) or its enantiomer. ... 

Polyhydroxylated Alkaloids. Polyhydroxy derivatives of pyrrolidine, piperidine, and indolizidine alkaloids have recently been isolated from plants and microorganisms. A number of these compounds have shown potent gluco-sidase inhibitory activity and have generated interest because of their ability to inhibit replication of retroviruses. 

Reversed-phase HPLC is the method recommended for the screening of plant materiaL in which chromone alkaloids can be present. Mostly C-18 columns were applied with aqueous mobile phases containing high concentrations of buffer at pH 4.5-6.5, modified with methanol or acetonitrile. Polyhydroxy alkaloids of the pyrrohdine, piperidine, pyrro-lizidine, indolizidine, and tropane classes, because of their lack of a suitable chromophore, have rarely been analyzed... 

All these advances allowed the preparation of a collection of polyhydroxy-lated piperidine, pyrrolidine, pyrrolizidines, indolizidine, and quinolizidine type iminocyclitols (e.g.. Scheme 16.9) which were widely investigated against a panel of commercial glycosidases as well as inhibitors of intestinal rat disaccharidases [16, 19, 21]. 

Four structural types of such alkaloids can be distinguished, namely polyhydroxy-derivatives of piperidine, pyrrolidine, indolizine and pyrrolmdine. 

---