Synthesis of lignans

Fig. 27 Cyclohexanone monooxygenase-mediated synthesis of lignan building blocks...

Honda T, Kimura N et al (1994) Chiral synthesis of lignan lactones, (—)-hinokinin, (—)-deoxypodorhizone, (—)-isohibalactone and (—)-savinin by means of enantioselective deprotonation strategy. J Chem Soc Perkin Trans 1 1043-1046... 

Asymmetric synthesis of lignans may involve the use of several approaches like a tandem conjugate addition reaction, a Diels-Alder reaction or a radical carboxyarylation reaction, as mentioned above. 

Other methods of preparation and diastereoselective alkylation of chiral butyrolactones (44) are summarized in the recent review of asymmetric synthesis of lignans (16). 

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... 

The demonstration of a diastereoselective C-H insertion to form the furofuranoid nucleus opens a way to total synthesis of lignans such as asarinin." ... 

Scheme (10). Asymmetric synthesis of lignans by Charlton and co-workers...

As the previous chapters have demonstrated, chiral auxiliaries have found a widespread application in the asymmetric synthesis of lignans. Among them, chiral oxazolidinones have been used extensively due to their ability to produce excellent diastereoselectivities in aldol as well as in numerous other reactions. For example, Kise et al. reported the use of (5)-4-isopropyl-3-(phenylacetyl)-2-oxazolidinone (141) in oxidative homocoupling reactions and its application in the asymmetric synthesis of dibenzylbutyrolactones and dibenzylbutandiols, Scheme (26) [86,87]. Treatment of 3-arylpropanoic acid derivative 142 with LDA in the presence of TiCU yielded a mixture of the dimeric compounds 143 in a ratio of 85 15 to 87 13. The major product having (R,R) configuration was converted into dibenzylbutyrolactones 145 in a three step sequence... 

Bisbenzocyclooctadienes The nonphenolic coupling used in the synthesis of lignan lactones is accomplished with Re207 in TFA-TFAA media. 

Oxidative dimerisation at the side-chain has been described as relevant to the synthesis of lignans (ref.75). Methyl 3,4-dimethoxybenzoylacetate in refluxing aqueous acetonitrile treated with potassium persulphate and a small amount of copper sulphate in an inert atmosphere produced after several hours (monitored by TLC), the dimer shown (racemateimeso 3 1) in 58% yield. 

BA 25. Piancatelli, G. Bella, M. Pigro, C. 3-Phenylselanyl-2(5H)-one a Versatile Building Block in the Synthesis of Lignans. A New Approach Towards 3,4-Dibenzyl -Butyrolactones Tetrahedron 1999, 55, 12387-12398... 

Another simple synthesis of lignans of the lariciresinol type (11) involves a straightforward reduction of a functionalised dibenzylbutyrolactone such as (75) or (76) followed by acid-catalysed cyclisation (scheme 24) [77,78]. Cyclisation of the doubly functionalised precursor (77) affords access to the furofuran skeleton (78) (scheme 25). A second synthesis which has also been extended to the furofuran series involves a radical cyclisation step, which proceeds with high stereoselectivity (scheme 26) [79]. This route has been used to synthesise (79) which is a precursor for the synthesis of sesamin and eudesmin [80]. 

Scheme 14.20 Synthesis of Lignan natural products through fS.SI-rearrangemenLs nf JV-allyl hydrazones. ...

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