Aryltetralins

Another group of natural products, namely the biologically active lignans of the aryltetralin series - for example, isopodophyllotoxone (2-59), picropodophyllone (2-60), and podophyllotoxin (2-61) (Scheme 2.13) [19] - have also been synthesized using a domino Michael/aldol process. 

Podophyllotoxin is an aryltetralin lignan which has been isoiated from severai plants of the Podophyllum species, it is a potent cytotoxic agent against various cancer celi iines, stopping the cell cycle in metaphase through the inhibition of microtubules assembly by binding the colchicine site of the tubulin [112]. Because of numerous side effects, podophyllotoxin cannot be used as a drug. 

Other atropisomer is not formed. b Byproduct is an aryltetralin (5%). c Other atropisomer is not formed [ H NMR (500 MHz)]. d No information about the formation of the other atropisomer is given. 

Oxidation of an allyiic ether. Oxidation of aryltetralin lignanes such as 1 results in two products, 2 and 3, which are believed to be formed as indicated in equation... 

A key step in the total synthesis of the indole terpene alkaloid a-cyclopiazonic acid was a carbocationic cascade (91) -> (92), terminated by a 4-nitrosulfonamide and initiated by a benzylic carbocation formed from an O-silyl precursor 243 An alkyla-tion-cyclization sequence for the preparation of 1-aryltetralins and 1-arylbenzopyrans... 

Diels-Alder reactions have been widely used to synthesize lignans, particularly the arylnaphthalene and aryltetralin types. This was one of the first examples of the use of an znfermolecular (as opposed to an intramolecular) Diels-Alder reaction for lignan synthesis. The approach includes the use of an arylisobenzofuran (Fig. 4) generated in situ as diene and dimethylacetyl-enedicarboxylate (DMAD) as the dienophile (Fig. 4). The Diels-Alder prod-... 

Aryltetralin lignans. This ring system can be prepared in high yield by a Prins reaction of a 1,4-diaryl-1-butene with paraformaldehyde catalyzed by an alkylaluminum halide prepared from CHjAlCh and (CH,) A1C1 (1 1), which is more acidic than (CHO AICI alone. 

Broomhead, A.J. and Dewick, P.M. (1990) Aryltetralin lignans from Linum flavum and Linum capitatum. Phytochemistry, 29, 3839-44. 

Federolf, K., Alfermann, A.W. and Fuss, E. (2007) Aryltetralin-lignan formation in two different cell suspension cultures of Linum album Deoxypodophyllotoxin 6-hydroxylase, a key enzyme for the formation of 6-methoxypodophyllotoxin. Phytochemistry, 68,1397-A06. 

Jackson, D.E. and Dewick, P.M. (1984) Biosynthesis of Podophyllum lignans. II. Interconversions of aryltetralin lignans in Podophyllum hexandrum. Phytochemistry, 23, 1037-12. 

Kamil, W.M. and Dewick, P.M. (1986b) Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry, 25, 2093 102. 

E Arylnaphthalenes F Aryldihydronaphthalenes G Aryltetralins H Tetrahydrofurofurans I Dibenzocyclo-octadienes J Diarylcyclobutanes... 

In certain cases, structure elucidation of aryltetralin lignans has only been established by total synthesis of the ( )-compounds. Noteworthy in this respect have been the constituents of Phyllanthus nlruri Linn. (Euphorbiaceae), extracts of which have been used medicinally (in treatment of asthma, jaundice and bronchial infections) (140). Considerable confusion resulted mainly from differing interpretations of spectroscopic data, and at least five different structures were proposed for the major constituent, hypophyllanthin. The structure of the aryltetralin constituents established by unequivocal synthesis (141) are shown in Scheme 30 they were given the names hypophyllanthin (1411. nirtetralin (1421. phyltetralin (1431 and lintetralin (1441. 

Aryl coupling to a benzylic site has also been observed the monophenol (67) yielded the aryltetralin (68 55%), with thallium trifluoroacetate-boron trifluoride. Probably oxidation to quinone methide precedes the ring closure. Separate oxidation and cyclization steps were employed in the synthesis of ( )-thaliphotphine acetate. ( )-Codamine (69) underwent Wessely oxidation with lead tetraacetate to the acetoxycyclohexadienone (70), which closed in acetic anhydride-acid to ( )-thaliphorphine acetate (71), albeit in modest overall yield (14%). ... 

Chart 16 CD Curves of 4-Aryltetralin Lignan in EtOH ---- hernandin (15) ------compound (58) ---------compound (59)... 

Synthesis of Related 4-Aryltetralin-Type Lignan from Desoxypodophyllotoxin... 

---