Biogenetic Hypotheses

The second experimental problem is that incorporation of a material such as loganin (34), or even an amino acid which seems cleady to be a precursor by some biogenetic hypothesis, does not necessarily prove it is a precursor. The material fed may so completely swamp the normal pathways in the plant that the utiliza tion of what was fed generates an aberrant path which nonetheless produces the same product. 

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... 

Extracts from young seedlings of Heimia salicifolia plants were the source of three minor alkaloids. Rother and Schwarting have isolated two isomeric 1-(12-hydroxy-13-methoxy)phenylquinolizid-3-ols (63a) and (64a) and detected 1-(12-hydroxy- 13-methoxy)phenylquinolizid-3-one (65a or 65b or both) (47, 48). These alkaloids were absent in extracts of plants obtained at later stages of growth (49). These three compounds are intermediates in the current biogenetic hypothesis. 

Occurrence of simple quinolizidone alkaloids, ester alkaloids, and lactonic alkaloids in the same Heimia salicifolia plant species provides further evidence in support of current biogenetic hypothesis. 

The common intermediate in two published biomimetic routes to Lythraceae alkaloids was substituted 4-phenylquinolizid-2-one. In one approach based on a biogenetic hypothesis of Ferris et al. (62), Wrobel and Gol biewski condensed pelletierine (126) with isovanillin (128) and obtained a transfused quinolizidine derivative (130, jS H-5) (64) in 75% yield. A model condensation of pelletierine (126) with benzaldehyde which resulted in a mixture of quinolizidones was reported earlier by Matsunaga et al. (65). In another approach Rosazza et al. (52) condensed A -pjperideine (132) with /J-ketoester 133 to get 134. The next stage in both approaches was reduction of the ketone and esterification or transesterification with derivatives of p-hydroxycinna-mic acid (135 or 136). Investigations into the oxidative coupling of 137 were unsuccessful. 

Gueritte-Voegelein, R, Guemard, D. and Potier, P. (1987) Taxol and derivatives a biogenetic hypothesis. /. Nat. Prod., 50,9-18. 

The biomimetic synthesis of this and related compounds has been completed using the bis-pyridinium cycle as a synthetic precursor of the corresponding cycle 78. The study has confirmed the previously proposed biogenetic hypothesis [38]. 

The first tentative biogenetic hypothesis was suggested by Cimino et al. for the saraines, haliclamines, xestospongins, and petrosins. The origin of these alkaloids can be envisaged as coming from reduced bis-3-alkylpyridine macrocycles. 

Scheme 1. Schmitz biogenetic hypothesis for the formation of (-)-longithorone A (1).

Location of the benzoyl moiety on the methylcyclohexene ring was established by analysis of the H-NMR spectrum of the alcohol obtained by hydride reduction (LiAlH4) of the hexamethyl ether (103b). Chalcomoracin (103) is optically active and is presumably formed by a Diels-Alder type reaction between morachalcone A (120) and dehyd-romoracin C (132) or their equivalents under enzymatic control. This biogenetic hypothesis is supported by the co-occurence of morachalcone A (120), moracin D (78) (82) equivalent to dehydromoracin C (132), and chalcomoracin (103) as minor phytoalexins in the infected cortical tissues of mulberry shoots. 

Kinjo, J., Uemura, H., Nohara, T., Yamashita, M., Marubayashi, N. and Yoshihira, K. 1995. Novel yellow pigment from Pterocarpus santahnus Biogenetic hypothesis for santaUn... 

Following these early studies, which appeared to provide support for the biogenetic hypothesis outlined in Schemes 36 and 39, tracer experiments were... 

The structures of all Lycopodium alkaloids isolated thus far may be accommodated within the polyacetate biogenetic hypothesis proposed by Conroy 27) which has been alluded to in earlier sections of this review. His scheme proposes that the alkaloids are formed from two 3,5,7-triketooctanoic acid chains. The manner in which the two chains combine is illustrated by the numbering system proposed b " Wiesner (26) and adopted in this review. The odd-numbered C atoms represent the acetate carboxyl and the even-numbered C atoms the acetate methyl groups. This biogenetic scheme was put forward at a time when the structures of only a few alkaloids were known annotinine, lycopodine, a- and j8-obscurine, and selagine. It is perhaps more than coincidental that it also accommodates the novel structural types found in cernuine and serratinine. 

The labelling pattern shown in Scheme 7 supports the novd biogenetic hypothesis that sterigmatocystin, as an early precursor of the aflatoxins. 

Based on a biogenetic hypothesis, the dimerization of vindoline and catharanthine into vinblastine (extracted from Madagascar periwinkle, Catharanthus roseus) [ROB 98], a synthetic scheme was developed using a crucial biomimetic coupling for the development of the molecule as a drug... 

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