Pyrrolidines polyhydroxy

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. ... 

When a mixture of acetic anhydride and trimethylsilyl triflate was used, the opening of the Cl - O bond took place to yield the corresponding acy-lated polyhydroxy pyrrolidines 11 as mixtures of a- and b-anomers [43], compounds of interest as potential glycosidase inhibitors. However, when the opening of the pyranose ring is carried out in methanol containing lithium perchlorate, followed by addition of a 2 1 mixture of TFA and trifluoroacetic anhydride, only 12 was obtained as a single diastereoisomer (Scheme 4). 

The synthesis of polyhydroxy pyrrolidines containing a hydroxymethyl branching group, starting from 3-deoxy-2-C-hydroxymethyl-D-ery Aro-pentono-1,4-lactone, is mentioned in Chapter 18 and the X-ray crystal structures of the same compound and of 3-deoxy-2-C-hydroxymethyl-D/L-tetrono-1,4-lactone are noted in Chapter 22. 

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. 

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. 

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. 

---