Tetralin lignans

Dayan, F.E., Kuhajek, J.M., Canel, G., Watson, S.B. and Moraes, R.M. (2003) Podophyllum peltatum possesses a p-glucosidase with high substrate specificity for the aryl-tetralin lignan podophyllotoxin. Biochim. Biophys. Acta, 1646,157-63. 

Puri, S. C., Nazir, A., Chawla, R., Arora, R., Riyaz-ul-Hasan, S., Amna, T, Ahmed, B., Verma, V, Singh, S., Sagar, R., Sharma, A., Kumar, R., Sharma, R. K., Qazi, G. N. The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related tetralin lignans. J. Biotech. 2006, 122, 494—510. 

We next turned our attention to the 1-arylnaphthalene and tetralin lignans (Fig, 13) which include podophyllo-toxin and many other important lignans, A model biomimetic sequence is shown in Scheme 20, This can be combined with tandem addition process to butenolide (vide infra), More generally our approach was to use butenolide as an example of a C -unit with opposite charges on adjacent carbon atoms (Scheme 21). As a model we used a dithane anion as the nucleophile and a benzyl bromide as the electrophile in tandem addition to butenolide. The reaction worked well to give the trans-fused product This seems... 

There has been much interest in the synthesis of lignan lactones of the aryl tetralin type, induced by the antitumour activity of podophyllotoxin relatives, and some short oxidative routes into the series have been pursued. In a typical reaction, in which both Cp—Cp and Cp—Car couplings occur, the cinnamyl cinnamate (297) was treated for 30 s with chromium trioxide-fluoroboric acid in acetonitrile. Three tetracyclic products were obtained, the lactones (298 19%) and (299 7%), and ( )-isopodophyllotoxone... 

In the mass spectra of compounds (1 5) and (36), as shown in Chart 8, not only the molecular ion peaks at m/z 428 but also other prominent ion peaks at m/z 260, 215, 203, 181 and 168 were common to both compounds. The mass spectra of analogous lignans have been reported by Duffield and Pelter (ref. 38). Therefore each fragment ion was assigned as shown in Chart 8b. The above results show that compound (1 5) has a trimethoxyphenyl group and a tetralin ring, and that a methoxy and a methylenedioxy group on the benzene nucleus. 

Hernandin (15) is a new compound which belongs to the category of phenyl-tetralin-type lignans. Many studies have been reported on the syntheses of this type lignans (ref. 2, 47), and some of them were carried out in connection with the syntheses of steganacin (ref. 48) and deoxyschizandrin (ref. 49). A route via an itaconic acid derivative, obtained by Stobbe condensation of a benzophenone derivative with diethyl succinate, followed by cyclization (ref. 41a, 50) was first undertaken through the scheme outlined in Chart 10. 

The aromatization reaction involving conversion of tetralin-type lignans to naphthaline-type lignans was unsuccessful, as described previously. Therefore it carried out using chloranil or DDQ for desoxypodophyllotoxin (3), its isomer (4)... 

This highly hydroxylated phenyl-tetralin-type lignan acid is available from Thuja plicata. It is recovered in about 2% yield from the heartwood. Because it is one of the strongest known natural acids, plicatic acid (6) is readily separable from... 

A rapid if not very efficient (23—46% yields) entry to cyclohex-3-en-1-ones (170) is by condensations between a-lithio-nitriles and buta-1,3-dienes.Two closely related methods involving Michael additions of 2-(2-lithiophenyl)ethyl halides leading to tetralin derivatives have been reported. Thus, condensation of (171) with the diester (172) results in the formation of the lignan precursor (173),while the aryl-lithium (174) reacts similarly with unsaturated sulphones (175 n = 1 or 2) to give (176) in high yields. " A further example of the... 

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