Diarylheptanoids biosynthesis

Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa U. (1992). Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm Bull (Tol o). 40(2) 387-91. Kobayashi M, Shqji N, Ohizumi Y. (1987). Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. Biochim Biophys Acta. 903(1) 96-102. 

Kiuchi, F., Iwakami, S., Shibuya, M., Hanaoka, F. and Sankawa, U. (1992) Inhibition of prostaglandin and leukot-riene biosynthesis by gingerols and diarylheptanoids. Chemical and Pharmaceutical Bulletin 40, 387-391. 

The constitution of this relatively simple and broadly used compound was established surprisingly late by Lampe and Milobedzka (2), first in 1910 by degradation followed in 1913 by a synthesis (3,4). Curcumin remained the only representative of the group as long as until 1964. In the following 30 years, however, about 70 linear and 35 macrocylic diarylheptanoids were isolated. In the present review we are dicussing their chemistry, phytochemistry, biosynthesis, biological activity, and synthesis. 

Two hypotheses have been proposed for the biosynthesis of diaiylheptanoids. Geissmann pointed out that a common feature of linear diarylheptanoids is oxygenation of the seven membered aliphatic chain at positions 3 and/or S, further double bonds at positions 1 and/or 6. This suggested that in the course of their biosynthesis diarylheptanoids are formed by the attachment of two cinnamate units to the central carbon atom of a malonate (82). 

Macrocyclic diarylheptanoids can be derived from linear ones by oxidative cyclization. This is supported by the fact that in all of the biaryl type representatives the aryl-aryl bond is in meta position relative to both ends of the seven-carbon chain, while in those containing a diarylether bond a meta,para bridging can be identified. This substitution pattern corresponds to activation of the position ortho to the phenolic hydroxy group. Biosynthesis of cyclic diarylheptanoids was investigated by Inoue et al. (84). They fed [1- C] and... 

Inhibition of PG biosynthesis by open chain diarylheptanoids was first reported by Itokawa and his coworkers (26, 31). Their results were implemented by studies on additional compounds first by Flynn (88) and later by Kinchi et al. (85). The latter group extended the assay of inhibitor activity also to the 5-lipoxygenase enzyme system. Their results are summarized in Table 2. Among macrocyclic diarylheptanoids only for garuganins (88-95), isolated from Garuga pinnata was some antiinflammatory activity claimed, but no specific data were disclosed (57, 58). 

Biosynthesis Two phenylpropane units are linked through C-2 of acetate to furnish a diarylheptanoid which is incorporated entirely in plant P. through intramolecular Diels-Alder cyclization. ... 

If the actual biosynthesis of the 9-phenylphenalenones is related to the scheme proposed by Thomas, then the cyclization of the diaryl-heptanoid intermediate [e.g. (73)] could proceed through the biosynthetic equivalent of a Diels-Alder reaction. As was mentioned on page 181, the diaryIheptadienone (65) has been synthesized and converted into lachnanthocarpone through the diarylheptanoid orthoquinone (66) in vitro (52). To the extent that this result shows that a 9-phenyl-phenalenone can be constructed from a suitable diarylheptanoid, it can be considered as adding support to Thomas hypothesis. 

Roughley P J, Whiting D A 1971 Diarylheptanoids the problems of the biosynthesis. Tetrahedron Lett 3741-3746... 

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