Pyrrolidine-containing ring systems

A variety of alkaloid skeletons can be prepared from 5-exo cyclizations of aminium cation radicals derived from PTOC carbamates, and some are listed in Table VI (90T2329). Perhydroindoles (entry 1), 1-, 2-, and 3-substituted pyrrolizidines (entry 2-4), tropanes (entry 5), and other pyrrolidine containing ring systems were obtained in 50-96% yields. Direct com-... 

X=NR) as a general method for forming pyrrolidines and pyrrolidine-containing ring systems. [8] We chose to examine the reaction of allylic acetals 1 (X = O) with acids in the expectation that they might be converted to 3-... 

Simple examples shown above are the base-catalysed formation of oxygen- and nitrogen-containing ring systems. We have shown base-initiated ionization of the alcohol to an alkoxide anion in epoxide formation the anion is a better nucleophile than the alcohol. For pyrrolidine synthesis, the amino group is sufficiently nucleophilic for reaction to occur, but base is required to remove a proton from the first-formed intermediate. 

These alkaloids contain pyrrole or modified pyrrole, e.g. pyrrolidine, ring system. The simplest example of this class is nicotine. A pyrrolidine ring is the central structure of the amino acids proline and hydroxyproline. These alkaloids are also found in many drug preparations, e.g. procyclidine hydrochloride, which is an antichohnergic drug mainly used for the treatment of drug-induced Parkinsonism, akathisia and acute dystonia. 

The tobacco alkaloids, especially nicotine, are derived from nicotinic acid (see page 311) but also contain a pyrrolidine ring system derived from ornithine as a portion of their structure. 

There are many abundant naturally occurring compounds containing a pyrrolidine ring system. Remarkably, however, syntheses of kainoids from such materials have received relatively little attention. An important... 

When the related aziridine 195 was used containing one less carbon in the tether, an unusual cyclization occurred which corresponds to a formal [3+2] aziridine allylsilane cycloaddition to give the bicyclic pyrrolidine 196. This substrate was used for the preparation of other fused ring systems (Scheme 53) <1999T8025>. 

Alkaloids that contain pyrrolidine and pyrrolizidine ring systems are derived from the nonprotein amino acid, L-ornithine. Cocaine (Nl) and (—)-hyoscyamine, the two important pyrrolidine alkaloids that contain a tropane ring system, have been found to occur in coca (Erythroxylon coca, Erythroxylaceae) leaves and the whole plant of the deadly nightshade (Atropa belladonna, Solanaceae). The hepatotoxic alkaloid senecionine (N2) contains a bicyclic pyrrolizidine skeleton derived from two molecules of L-ornithine. 

Wang and co-workers further broadened the application of Cu(I)/TF-BiphamPhos catalyst system to the first catalytic asymmetric 1,3-dipolar cycloaddition of homoserine lactone-derived cychc aldimino esters with dimethyl maleate for the highly efficient synthesis of biologically active spiro-[butyrolactone-pyrrolidines] containing both a y-lactone and pyrrolidine moiety (Scheme 23) [43]. A key feature of this method is that the lactone ring in the generated spirocycles is provided by the dipole, rather than by the dipolarophile. 

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