Furofuran lignans

Upon supplementing the first alkylation by an aldol reaction, other types of a-hydroxylated lignans should be attainable as well. In the case in which both C-C bond formations are aldol reactions, furofuran lignans, such as paulownin or analogs, should be obtained. On the other hand, aldol addition... 

Dianion aldol condensation reactions with Evans oxazolidinones or Oppolzer sultams as chiral auxiliaries have been demonstrated to be a useful method to generate the core skeleton of furofurans with diastereoselectivities of 5 1-20 1. Stereoselective total syntheses of the furofuran lignans (-l-)-eudesmin, (+)-yangambin, (—)-eudesmin, and (-)-yangambin according to this procedure have been reported (Equation 102) <2006TL6433>. 

The non-phenolic furofuran lignan, (-l-)-eudesmin, from Magnolia kobus var. borealis is formed from pinoresinol by two SAM-dependent methylation steps (Miyauchi and Ozawa, 1998). Cell-free extracts catalysed the successive non-stereospecific methylation both of (-1-)- and (—)-pinoresinol. Thus, the stereospecificity has to be established in an earlier step. 

Ono, E., Nakai, M., Fukui, Y, Tomimori, N., Fukuchi-Mizutani, M., Saito, M., Satake, H., Tanaka, T., Katsuta, M., Umezawa, T. and Tanaka, Y. (2006) Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)—sesamin. Proc. Natl. Acad. Sci. USA., 103,10116-21. 

An interesting application of the asymmetric alkoxyselenenylation of alkenes to natural product synthesis was reported recently by Wirth, who described a short procedure to obtain some furofuran lignans 147]. The total synthesis of (+)-Samin 53 [47 a] is shown in Scheme 7. The protected allylic alcohol 50 was treated with the selenyl triflate derived from diselenide 29 in the presence of 2,3-butadien-l-ol, and afforded the addition product 51 in 55% yield and with a diastereomeric ratio of 15 1. The favored 5-exo-trig radical cyclization of the major isomer afforded the tetrahydrofuran derivative 52 from which the final product was obtained through few classical steps. 

Swain, N. A, Brown, R. C. D., Bruton, G. A Versatile Stereoselective Synthesis of endo,exo-Furofuranones Application to the Enantioselective Synthesis of Furofuran Lignans. J. Org. Chem. 2004, 69,122-129. 

Stereocontrolled syntheses of unsymmetrically substituted furofuran lignans 00H(52)1399. 

Yangambin is a furofuran lignan with PAF antagonist properties that seems to also have anti-allergic properties. In a study with actively sensitised or normal rats, Serra et al. [290] demonstrated that yangambin inhibited the pleural neutrophil and eosinophil infiltration evoked by injection of PAF or antigen and the pleural neutrophil infiltration triggered... 

Radical addition to carbon-carbon unsaturated bonds has also been carried out in microflow reactors. Tributyltin hydride-mediated radical reactions of organic halides have been successfully carried out in a continuous microflow system [20]. Rapidly decomposing radical initiators such as V-65 and V-70 are fairly effective and the reactions proceed within a very short period of time. The continuous flow reaction system can be applied to gram-scale synthesis (7.6 g, 185 min) of a key intermediate for furofuran lignans (Figure 5.2). 

---