Structure Determination of Enmein in Outline

Investigations on the structure of enmein were carried out by many Japanese researchers. Enmein isolated from R. trichocarpa is usually contaminated by dihydroenmein and complete separation of the two compounds is difficult. On the other hand, R.japonica does not contain dihydroenmein and thus pure enmein can be isolated more simply from its leaves (5). Enmein, C20H26O6, has mp 308—312° (decomp.) and [aJo —136.3 °. UV and IR spectra showed 233 nm ( 8200) and Vj ax 3460, 1755, 1710, and 1640 cm  

Research on the structure determination of enmein consisted of three stages. In 1958, isolation, characterization of five of the six oxygen atoms, and proposals for a partial structure were reported by three groups at Kanazawa University (9, 10), Osaka City University (77) and Kyoto University (12—14). The functional groups assumed by the three groups are summarized below (I). 

In 1961, two experiments which provided the basis for deducing the skeleton of enmein were carried out by Kanatomo (75, 16). In the first he obtained l-ethyl-4(3,3-dimethylcyclohexyl)-benzene (II) whose structure was proved by synthesis (75). In the second he isolated retene (III) by selenium dehydrogenation of the material obtained by LiAlH4 reduction of enmein (16). Thus enmein was proved to be a diterpene and a phyllocladene (IV) skeleton was proposed for it (16). Kubota and coworkers (77) deduced the presence of a hemiacetal ring (V) and partial structure (VI), with the lactone function part of a six-membered ring, on the basis of chemical evidence and spectral data of various derivatives, and advanced four formulas including (VII) as possible structures for enmein. 

Finally in 1964, cooperative studies of the three research groups resulted in a successful conclusion to this part of the work. On the basis of chemical reactions and the spectroscopic properties of the transformation products, the planar structural formula of enmein was shown to be (VII) with stereochemistry (Villa) or the C-9 epimer (VIIIb) 18, 19). At the same time, an X-ray analysis of dihydroenmein 3-acetate 6-bromoacetate permitted depiction of the structure and absolute configuration of enmein as (Villa) 20). A review of this work by Uyeo has been published (27). 

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