The Pyrrolidine Alkaloids

In order to synthesise the pyrrolidine alkaloid, (-l-)-197B, bis-(i ,i )-tri-fluoromethanesulfonamide ligand was employed in the enantioselective addition of Zn( -Bu)2 to an allene-aldehyde, alfording the corresponding (i )-alcohol in 70% yield and 94% ee (Scheme 3.52). ... 

Although no experiment has yet been reported to support the idea, it seems clear that a majority of the pyrrolidine alkaloids arise from the ornithine, pu-trescine, and proline pool. This could be the case for ficine (61) and isoficine (62), vochysine (63), and phyllospadine (64) but also of the Darlingia alkaloids, which share common features with hygrine this assertion probably also holds for the ruspolinone (25) and odorine-roxburghlin (59) families. Peripentadenine, isolated from a plant of the family Elaeocarpaceae, bears resemblance to other alkaloids of the elaeocarpus type such as isoelaeocarpicine (124) (161). It cannot be excluded, however, that spermidine may be a biosynthetic intermediate instead of putrescine. The question of the origin of ant alkaloid substances remains so far without an obvious answer. 

The preparation of a special chapter in this series on the constituents of pepper (6) led us to ignore pepper alkaloids. After publication of the chapter, we discovered that it dealt with the alkaloids of red pepper species (Capsicum, So-lanaceae), which are not pyrrolidines, and the purpose of this addendum is to provide a survey of the pyrrolidine alkaloids contained in black pepper species Piper, Piperaceae. 

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

Just as terpenes could be viewed as being formed from isoprene units, alkaloids can be viewed as being derived from amino acids. Four amino acids give rise to important classes of alkaloids. As shown in Table 28.1, the pyrrolidine alkaloids are derived from the amino acid ornithine (not one of the 20 standard amino acids), the piperidine alkaloids from lysine, the isoquinoline alkaloids from tyrosine, and the indole alkaloids from tryptophan. 

Pyridoxal-media ted decarboxylation of dopa gives dopamine and this reacts with the keto-acid to form an imine salt. This is an open-chain inline salt unlike the cyclic ones we saw in the pyrrolidine alkaloids, but it will prove to have similar reactivity. 

The imine salt is perfectly placed for an intramolecular electrophilic aromatic substitution by the electron-rich dihydroxyphenyl ring. This closes the isoquinoline ring in a Mannich-like process (Chapter 27) with the phenol replacing the enol in the pyrrolidine alkaloid biosynthesis. 

The first step is the Claisen ester condensation of two molecules of acetyl CoA, one acting as an enol and the other as an electrophilic acylating agent to give acetoacetyl CoA. We saw the same reaction in the biosynthesis of the pyrrolidine alkaloids earlier in this chapter. 

The piperidine alkaloids were mentioned in the chapter (p. 1418) where the pathway was described as similar to that of the pyrrolidine alkaloids . We can follow the same reactions starting from lysine instead of ornithine. The first stage produces the cyclic iminium salt fi om lysine by decarboxylation with pyridoxal. 

A number of difficulties exist with this postulate. Stermitz1 group has shown that fresh aerial parts of field bindweed (Convolvulus arvensis) contain pseudotropine as the major alkaloid, together with trace amounts of tropine and tropinone, as well as the pyrrolidine alkaloids hygrine and... 

Also the hydroamination/cyclization of chiral aminoallenes has been utilized in the synthesis of various alkaloid skeletons [120]. The pyrrolidine alkaloid ( + ) 197B (Scheme 11.25), as well as the indolizidine alkaloid (+) xenovenine (Scheme 11.26),... 

In the few years since the chapter on the pyrrolidine alkaloids was written they have not been the subject of much additional work. The recent investigations to be described relate to hygrine, hygroline, cuscohygrine, stachydrine, betonicine, and turicine. The structure of carpaine has also been fully elucidated, and this alkaloid has been shown to be a piperidine and not a pyrrolidine alkaloid and hence will be described under the heading The P3addine Alkaloids. ... 

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