Biosynthesis of Dendrobines

Again using the cotton-wick method, 0.95% incorporation in dendrobine (82 ) and 0.71% incorporation in nobilonine (90 ) were found (225). Labelling of the 

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Yamazaki M, Matsuo M, Arai K (1966) Biosynthesis of Dendrobine. Chem Pharm Bull 14 1058... 

Information on the direct route to the copacamphane skeleton has been obtained by studies on the biosynthesis of dendrobine (39), an alkaloid found in the orchid Dendrobium nobile, and related compounds (1969, 1972, 1973). The presumed route to (39) is shown in Scheme 7 and studies with (3K,55)-[5- Hj]MVA and its (5/ )-isomer have now revealed that a 1,3-hydride shift to the side-chain (previously demonstrated in 1973) involved the same epimeric hydrogen at C-5 of MVA as shifted in the formation of sativene. 

Corbella A, Gariboldi P, Jommi G (1973) Aspects of the Biosynthesis of the Terpenoid Dendrobine. J Chem Soc, Chem Commun 729... 

Experimental verification for the proposed 1,3-hydrogen rearrangements above has recently been obtained in the biosynthesis of avocettin (cadinene-based sesquiterpene) (109), sativene (109), longifolene (109), dendrobine (derived from copaborneol) (20, 140), tutin (derived from copaborneol) (176,177), and culmorin (derived from longiborneol) (178). 

CoRBELLA, A., P. Gariboldi, G. Jommi, and M. Sisti Biosynthesis of the Terpenoid Dendrobine. Early Stages of the Pathway. Chem. Commun. 1975, 288. 

The first report of the incorporation of radioactively labelled mevalonic acid into dendrobine (82) was by Yamazaki et al. (224). Sodium [2— CJmevalonate [( )-463 ] was administered to stems of D. nobile by the cotton-wick method. After 12 days, the plants were extracted and radioactive dendrobine (82) was isolated by column chromatography. The total incorporation was 0.012%. Subsequent Kuhn-Roth oxidation led to acetic acid that showed the expected activity assuming the biosynthesis pathway a leading to the picrotoxanes via a cadalene as precursor (Scheme 55, pathway c). 

Although investigations of biosynthesis have become considerably more convenient by shifting to stable isotopes and nondestructive spectroscopic methods, the pioneering work was never continued. Thus, the pathway from copabomeol (474) to dendrobine (82), mono- and dilactone picrotoxanes, and norditerpene picrotox-anes is stiU unknown and no enzymes of this biosynthetic pathway have been defined or isolated. There is mention of genes of the dendrobine bios3mthesis isolated and expressed in Escherichia coli (233). 

H2 mevalonate label located at C-8 in (4.81) , five out of the six labels were retained]. A 1,2-shift of hydrogen was excluded in tutin biosynthesis, 2-transr rather than 2-m-farnesol is a precursor for dendrobine (4.81) and further results show that it is the farnesol (l-/ ro-/ )-hydrogen atom which migrates to C-8 in (4.81). The deduced pathway to dendrobine and related sesquiterpenes is summarized in Scheme 4.16 (cf. Scheme 4.17) [85-88]. 

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