Pyrrolidine, pyrrolizidine

The dipolar cycloaddition of nitronates has been applied to the synthesis of several natural products in the context of the tandem [4+2] / [3 + 2] nitroalkene cycloaddition process. All of these syntheses have focused on the construction of pyrrolidine, pyrrolizidine, and indolizidine alkaloids. For example, the synthesis of ( )-hastanecine (316), a necine alkaloid, involves the elaboration of a p-benzoy-loxynitroalkene 311 via [4 + 2] cycloaddition with a chiral vinyl ether (312) in the presence of a titanium based Lewis acid, to provide the nitronate 313 with high diastereo- and facial selectivity (Scheme 2.30) (69). The dipolar cycloaddition of... 

Chapter 3. Pyrrolidine, pyrrolizidine, pyridine, piperidine and quinolizidine... 

PYRROLIDINE, PYRROLIZIDINE, PYRIDINE, PIPERIDINE AND QUINOLIZIDINE ALKALOIDS... 

Abstract This review is devoted to the stereoselectivity of intermolecular (intramolecular cycloadditions are not included) 1,3-dipolar cycloadditions of sugar-derived nitrones. Stereoselective cycloaddition (transformation of isoxazolidine followed by reduction of the N O bond to produce both an amino and a hydroxy function) allows the synthesis of tailor-made products of possible biological interest such as pol>4iydroxylated pyrrolidines, pyrrolizidines, indolizidines, fi-aminocarbonyl compounds, and disaccharides. Attention is focused on the preparation of isoxazolidinyl nucleosides and to the catalysis of the cycloaddition by Lewis acids. This review has concentrated on the new developments achieved from 1999 to February 2007. 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

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]. 

Formation of spiro-pyrrolidines/pyrrolizidine has been achieved under micro-wave exposure by using the alkene unit of Baylis-Hillman adduct of ninhydrin with sarcosine/proline and various activated ketones through 1,3- dipolar cycloaddition reactions (Ramesh et al., 2007). 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

Similar strategies have been used for the synthesis (286) of the tetrahydro-pyrrolizidine 323 from 2,3 5,6-di-O-isopropylidene-D-g/yccroD-ta/o-hep-tono-1,4-lactone (322). These polyhydroxylated pyrrolidines and pyrrolizi-dines are potential specific inhibitors of glycosidases. The stereochemistry of the hydroxyl groups have a profound effect on the selectivity of the inhibition (286-288). 

Several species pertaining to the sub-family Myrmicinae (e.g., Solenopsis spp., Monomorium spp.) are characterized by a venom rich in dialkylated saturated nitrogen heterocycles (e.g., piperidine, pyrrolidine, indolizidine, pyrrolizidine). Exhaustive lists of these alkaloids have already been published [114-116]. Since then, only a few more of these alkaloids have been reported from a few further species. 

Figure 11. L-ornithine is an important precursor of pyrrolidine, tropane and pyrrolizidine alkaloids.

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