Calycanthaceous alkaloids

Fig. 9.1 Representative dimeric hexahydropyrroloindole alkaloids, (a) Dimeric epipolythiodiketopiperazine alkaloids, (b) Calycanthaceous alkaloids, (c) Dimeric diketopiperazine alkaloids...

These epipolythiodiketopiperazine alkaloids, together with the calycanthaceous alkaloids (Fig. 9.1b), form a superfamily of natural products termed the dimeric hexahydropyrroloindole alkaloids [6-8]. The main dichotomy within this superfamily arises from the biogenetic elaboration of tryptamine versus tryptophan building blocks. The tryptamine-based calycanthaceous alkaloids, boasting members such as chimonanthine (7), calycanthine (9), and folicanthine (8), are largely plant derived and have a long and rich history in the context of natural product synthesis [7, 9]. 

L-tryptophan is compulsory, the biosynthetic machinery displays wide latitude in its ability to condense a second auxiliary amino acid—L-alanine in the case of (+)-ll,ll -dideoxyverticillin A (1)—to afford a tryptophan-derived diketopiperazine intermediate 13. Mirroring Woodward and Robinson s biogenetic hypothesis for the calycanthaceous alkaloids, single-electron oxidation of the electron-rich tryptophan residue would likely initiate an oxidative dimerization of the diketopiperazine precursor with concomitant cyclization to yield the octacyclic intermediate 17. Subsequent A-methylation of the amides would then yield an unembellished skeletal core of the dimeric epipolythiodiketopiperazine alkaloids. The first step en route... 

Hodson H F, Robinson B, Smith G F 1961 Chimonanthine, a new Calycanthaceous alkaloid. Proc Chem Soc 465-466... 

May JA, Stolz B. The structural and synthetic implications of the biosynthesis of the calycanthaceous alkaloids, the communesins, and nomofungin. Tetrahedon 2006 62 5262-5271. 

On the basis of structure the dimers can be clearly divided into two groups. The first is comprised of alkaloids with identical or very closely related components in which the same centres act as linkage positions. The Calycanthaceous and Calabash-curare-South American Strychnos alkaloids make up this group. The second group consists of dimeric bases in which the alkaloid components are of a different structural type (e.g. geissospermine, vinblastine, and tubulosine) or in which two similar halves are linked unsymmetrically through two different centres e.g. macralstonine). The bisindole alkaloids will be discussed in this order. ... 

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