Configurations of pyrrolizidine bases

The absolute configurations of pyrrolizidine bases were established only very recently. Leonard84 attempted to solve the problem by comparing the shifts of molecular rotation of isoretronecanol derivatives with analogous shifts in the lupinine series. However, it was demonstrated later that this approach led to incorrect conclusions. 

The absolute configuration was also established unequivocally for C-8 of naturally occurring pyrrolizidine bases.88 It was demonstrated in the course of the structural analysis of isoheliotridene (146), obtained by degradation of the alkaloid monocrotaline, that ozonolysis of this compound affords 2-acetylpyrrolidine-l-acetic acid (147).66 The (— )-methyl ester of this acid was condensed with methylmagnesium iodide to give (— )-l-(2-hydroxy-2-methylpropyl)-2-(l-hydroxy-l-methylethyl)pyrrolidine (148). The same glycol (148) was obtained... 

The absolute configurations of the alkaloid 1-methylenepyrrolizi-dine and related naturally occurring pyrrolizidine bases were also established by stereospecific synthesis.89... 

There are four known, naturally occurring fully saturated pyrrolizidine diols. The relative stereochemistry of platynecine (43) is known from chemical interconversions of the bases, and the absolute configuration was defined by degradation of heliotridane (7) to S-(-i-)-3-methylheptane. ... 

There are only two known, naturally occurring trihydric saturated pyrrolizidine bases. The relative stereochemistry of rosmarinecine (123) was determined by Warren and co-workers.78 For the other base, croalbinecine (124), the chirality at C-l, C-7, and C-8 was defined by Sawhney et al.19 by correlation with turneforcidine (113) as shown in Eq. (33). The location of the third hydroxy group at C-2, indicated by NMR spectroscopy, was confirmed by decoupling experiments. It was further suggested by these workers79 that the configuration at C-2 is /i-hydroxy, on the basis of the... 

Fig. 10. Structures of 3,5-disubstituted pyrrolizidines from dendrobatid and ranid frogs andbufonid toads (31,73,81, and J. W. Daly, H. M. Garraffo, andT. F. Spande, unpublished). Absolute configurations are unknown. It is assumed, based on analogy to other amphibian alkaloids, that n-alkyl side chains are present. The configurational nomenclature for these pyrrolizidines follows the system devised by Sonnet el at. (122) for 3,5-disubstituted indolizi-dines where the H-S and H-8 configurations are related to that at H-3 and are either cis (Z) or trans (E).

DCP-hased Chiral Auxiliaries in Total Synthesis. DCP-based chiral auxiliaries have proven amenable to asymmetric total synthesis, including Denmark s syntheses of of the pyrrolizidine alkaloid (-)-rosmarinecine and the pentahydroxy pyrrolizidine alkaloid (+ )-casuarine. Denmark s synthesis of (+)-casuarine involves [4 + 2] cycloaddition of dienophile 15 with nitrobenzoate followed by [3 + 2] cycloaddition of the resulting nitronate 17 with a vinyl silane 18 (eq 10). During formation of the [4 + 2] cycloadduct, the relative configuration between C4 and C5 is a direct consequence of the vinyl ether geometry, while the stereochemistry at C6 is determined by the ability of the chiral auxiliary to differentiate the diastereotopic n faces (Re of Si) of the vinyl ether (termed internal diastereoselection). Thus, this tandem sequence... 

A number of closely related naturally occurring pyrrolizidine cyclic ethers have been identified.74 Four of these, loline (=festucine75) (119), norloline (120), lolinine (121), and decorticasine (122), have had their structures and relative configurations established by chemical methods. In addition, the relative stereochemistry of loline has been defined by an X-ray crystal structure determination of its dihydrochloride.76 The absolute configurations for all these alkaloid bases have now been established by the X-ray technique of anomalous dispersion using the same dihydrochloride of loline (119).7 7... 

There has been no report so far of a synthesis of (+)-hyacinthacines Ci, C4, and C5 bearing substituents at each carlxMi of the pyrrolizidine skeleton. Therefore, their absolute configurations have yet to be determined. Yu and colleagues described recently the total synthesis of the proposed structure of ( )-hyacinthacine C5 [21] based on an original nucleophilic addition of a dithiane onto the xylose-derived nitrone 62 followed by a Cope-House cycli-zation (Scheme 13). 

Fig. 3.30 Unique platynedne-based pyrrolizidine alkaloids occurring in species of the intrageneric Ipomoea taxon subgenus Quamoclit, section Mina (Convolvulaceae) necine base residues = absolute configuration, aliphatic necic acid residues = relative configuration...

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