Naturally occurring pyrrolizidines

Pyrrolizines, partially reduced pyrrolizines, benzopyrrolizines, and pyrrolizinones are covered in this chapter however, the chemistry of naturally occurring pyrrolizidines and analogous compounds is beyond the scope of this chapter. 

More recently, Naidu and West have utilized a ring expansion reaction of spiro azetidinium ylide 167 in the synthesis of pyrrolizidine alkaloids. Spiro azetidinium ylide 167 is generated through a Cu(acac)2-catalyzed intramolecular reaction of a copper carbene complex with a pendant amino moiety. Subsequent [l,2]-shift gives fused bicyclic products 168 and 169 as a diastereomeric mixture. Each diastereomer was further converted to naturally occurring pyrrolizidines ( )-turneforcidine and ( )-platynecine, respectively (Scheme 18). ... 

As already mentioned, this route has been especially important for the preparation of naturally occurring pyrrolizidine bases. Recently, it afforded synthetic 1-hydroxymethylpyrrolizidine, 1-hydroxy-methyl-7-hydroxypyrrolizidine,andl-hydroxymethyl-7-hydroxy-l,2-dehydropyrrolizidine (retronecine). 

Rapid advances in the synthesis of naturally occurring pyrrolizidine bases can be expected, and the most promising method for this purpose is the Dieckmann cyclization of pyrrolidine derivatives. 

The synthesis of pyrrolizidine derivatives by condensation of di-(4-oxo-ra-butyl)amine is considered in Section V in conjunction with the biogenesis of naturally occurring pyrrolizidines. 

Pyrrolizidine derivatives with at least one substituent, and particularly the pyrrolizidine alkaloid components, have one or more asymmetric carbon atoms. The stereochemistry of pyrrolizidine was clarified for the most part in the course of investigation of the naturally occurring pyrrolizidine alcohols. Here, the problems of relative and absolute configuration and of stereoisomeric transformations will be considered. 

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... 

The chemical behavior and reactions of pyrrolizidine derivatives were investigated for the most part during structural analysis of naturally occurring pyrrolizidine alkaloids and in the course of the syntheses of their degradation fragments there are several publications concerned specially with this subject. Pyrrolizidine derivatives are typical tertiary amines, and consequently their chemical behavior is a combination of the properties of tertiary amines and of those of the substituent functions. However, some peculiarities of the class can be explained only in terms of the configuration of the bicyclic system. 

Biogenetic pathways leading to naturally occurring pyrrolizidine bases were proposed by Robinson, Schopf, and Lukefi (see, e.g., refs. 119-121) in their publications concerned with the biogenesis of alkaloids. The most probable precursors of the pyrrolizidine system are commonly accepted to be ornithine (176), hydroxyomithine (177), and their biogenetic equivalents. It is noteworthy that ( + )- -hydroxy-jV-methylnorvaline (178) (structurally related to ornithine) was isolated... 

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

Most of the spectroscopic information available is concerned with the naturally occurring pyrrolizidine alkaloids and their constituent acidic and basic moieties. This material has been well documented, and new data are... 

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... 

Rizk, A.-F.M. Naturally Occurring Pyrrolizidine Alkaloids-, CRC Press Boca Raton, FL, 1991. 

B-90M1 801-02 A. F. M. Rizk Naturally Occurring Pyrrolizidines. CRC Press, Inc., Boca Raton, FL,... 

A large number of naturally occurring pyrrolizidine compounds are known, and the C spectroscopy of these compounds has been extensively reviewed <83H(20)863, 90Pli>. Typical chemical shifts for these types of alkaloids are around 137 ppm for C-1, 125 ppm for C-2, 60 ppm for C-3, 55 ppm for C-5, 25-35 ppm for C-6, and 75 ppm for C-7a. C-7 is often oxygenated with chemical shifts around 75 ppm, but some nonoxygenated derivatives have been reported with chemical shifts for C-7 of around 30 ppm. 

Rizk AFM (1991) Naturally occurring pyrrolizidine alkaloids, CRC Press, Boca Raton... 

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