Stereochemistry of Pyrrolizidine Bases

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.  

The amino alcohol obtained by hydrolysis of the alkaloid retusine has been shown to be identical with turneforcidine (113), even though different specific rotations were originally reported for each compound. Turneforcidine must have the relative stereochemistry shown in 113, because it is a different compound from hastanecine (104), platynecine (43), and dihy-droxyheliotridane (108). The absolute configuration of 113 was indicated by preparation of the enantiomer of turneforcidine from platynecine (43) as outlined in Eq. (30). Proof of the absolute configuration of 113 was obtained by Aasen and Culvenor by their preparation of turneforcidine from an 

A number of closely related naturally occurring pyrrolizidine cyclic ethers have been identified. Four of these, loline ( = festucine ) (119), norloline 

There are only two known, naturally occurring trihydric saturated pyrrolizidine bases. The relative stereochemistry of rosmarinecine (123) was determined by Warren and co-workers. For the other base, croalbinecine 

The absolute configuration of (—)-supinidine (96) was established following the degradation of heliotridane (7) to S-(-f-)-3-methylheptane mentioned earlier (Section III,A). More recently, the enantiomeric (-1-)-supinidine has been isolated by Culvenor and Smith. This represents the first occurrence of an allylic amino alcohol derived from 8) -pyrrolizidine. 

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 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 

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The only example of this type of base is crotanecine (126), and its structure and stereochemistry were deduced by comparison of its NMR and mass spectra with those of the most widespread pyrrolizidine base, retronecine (127).84 The magnitude of the vicinal coupling constants of the protons on C-5 of crotanecine (126), 75 6 = 9.5 Hz and 75a 6 = 6.5 Hz, are consistent with the 6/ -hydroxy group and an exo-buckled ring. The other vicinal coupling constants, J6x l = J18 = 3.5 Hz are indicative of a 7/ -hydroxy group, as in retronecine (127). 

One of the main features of this review is the inclusion of three comprehensive Tables (Section VIII). All of the plant genera from 13 plant families known to contain pyrrolizidine alkaloids are listed in Table 1. Up to 1955, pyrrolizidine alkaloids were known to be present in 70 plant species (310)-, by 1966, the number had risen to 130 311) during the last 15 years 240 more species have been shown to contain pyrrolizidine alkaloids. These are listed with alkaloid content in Table 2. Likewise, there were about 50 known pyrrolizidine alkaloids in 1955, 100 by 1966, and now the total stands in excess of 200. The structures of these alkaloids appear in Table 3 classified according to the necine base they contain. It should be noted, that in many cases the stereochemistry of the acidic and base portions has not yet been established. 

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... 

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