Total lignans

Xu, Z., Ju, J., Wang, K., Gu, C., Feng, Y Evaluation of hypoglycemic activity of total lignans from frucms arctii in the spontaneously diabetic goto-kakizaki rats. J. Ethnopharmacol. 151(1), 548-555 (2014)... 

Phloem powder is rich in different types of fibers, lignans and polyphenols (Table 14.1). Phloem contains 58 g of fiber per 100 g, of which 51 g is insoluble and a lesser amount ( 7 g) is water-soluble. The total amount of different lignans in phloem is 79.3 mg/100 g, consisting mainly (98%) of secoisolariciresinol. The main flavonoids in phloem are catechins, and the... 

Using this system, (Z)-hinokiresinol isolated from cultured cells of A. officinalis was determined to be the optically pure (75 )-isomer, while ( )-hinokiresinol isolated from cultured cells of C. japonica had 83.3% e.e. in favor of the (7S)-enantiomer (Table 12.1). The enzymatically formed (Z)-hinokiresinol obtained following incubation of p-coumaryl p-coumarate with a mixture of equal amounts of recZHRSa and recZHRSf) was found to be the optically pure (75)-isomer, which is identical to that isolated from A. officinalis cells (Table 12.1). A similar result was obtained with the crude plant protein from A. officinalis cultured cells, where the formed (Z)-hinokiresinol was almost optically pure, 97.2% e.e. in favor of the (75)-isomer (Table 12.1). In sharp contrast, when each subunit protein, recZHRSa or recZHRSP, was individually incubated with p-coumaryl p-coumarate, ( )-hinokiresinol was formed (Table 12.1). The enantiomeric compositions of ( )-hinokiresinol thus formed were 20.6% e.e. (with recZHRSa) and 9.0% e.e. (with recZHRSP) in favor of the (7S)-enantiomer (Table 12.1). Taken together, these results clearly indicate that the subunit composition of ZHRS controls not only cis/trans selectivity but also enantioselectivity in hinokiresinol formation (Fig. 12.3). This provides a novel example of enantiomeric control in the biosynthesis of natural products. Although the mechanism for the cis/trans selective and enantioselective reaction remains to be elucidated, for example by x-ray crystallography, the enantioselective mechanism totally differs from the enantioselectivity in biosynthesis of lignans, another class of phenylpropanoid compounds closely related to norlignans in terms of structure and biosynthesis. 

Beracierta AP, Whiting DA (1978) Stereoselective total syntheses of the ( )-di-0-methyl ethers of agatharesinol, sequirin-A, and hinokiresinol, and of ( )-tri-0-methylsequrin-E, characteristic norlignans of Coniferae. J Chem Soc Perkin Trans 1 1257-1263 Birch AJ, Liepa AJ (1978) Biosynthesis. In Rao CBS (ed) Chemistry of lignans. Andhra University Press, Andhra Pradesh, pp 307-327... 

C-H activation at a primary benzylic site was the key step in very short syntheses of lig-nans 206 and 207 (Scheme 14.27) [138]. Even though both the substrate 203 and the vinyl-diazoacetate 204 contain very electron-rich aromatic rings, C-H activation to form 205 (43% yield and 91% ee) is still possible because the aromatic rings are sterically protected from electrophilic aromatic substitution by the carbenoid. Reduction of the ester in (S)-205 followed by global deprotection of the silyl ethers completes a highly efficient three-step asymmetric total synthesis of (-i-)-imperanene 206. Treatment of (R)-205 in a more elaborate synthetic sequence of a cascade Prins reaction/electrophilic substitution/lacto-nization results in the total synthesis of a related lignan, (-)-a-conidendrin 207. 

Rabbits fed a 0.5% cholesterol diet had atherosclerotic plaques on over 50%i of the aorta surface whereas the 0.5% cholesterol plus 40 mg lignan complex/kg body/per day reduced atherosclerosis by 34.4% (Prasad, 2005). Furthermore, the added lignan complex lowered the total cholesterol, LDL cholesterol, serum, and aortic malondialdehyde by 20%, 14%, 35%, and 58%, respectively. Unlike previous studies, the lignan enhanced HDL cholesterol by 25% and 30% in normocholesterolemic and hypercholesterolemic rabbits, respectively. Slightly higher (33% and 35%) reductions in total cholesterol and LDL cholesterol, respectively, were observed in rabbits on a 1% cholesterol diet containing 15 mg SDG/kg/day (Prasad, 1999). A 73% reduction in atherosclerosis was observed in the rabbits given the SDG diets compared to the 1% cholesterol diets. 

Thompson et al. (2005) reported that tumor cell proliferation and c-erbB2 expression decreased by 34% and 71%, respectively, whereas cell apoptosis increased (31%) in menopausal women fed a diet containing 25 g of flaxseed. Changes in c-erbB2 score and apoptosis index were correlated with total flaxseed intake whereas cell proliferation, as measured by Ki-67 labeling index, was not. A main conclusion from these studies was that the lignans and, to a lesser extent, ALA were responsible for the anticarcinogenic activity. 

In contrast to lignans, few studies have been reported regarding the relationship between ALA and breast cancer. In a meta-analysis, Saadatian-Elahi et al. (2004) reported a significant protective effect of total n-3 fatty acids and breast cancer risk. In this assessment, three cohort and seven case-control studies were reviewed. The case-control studies revealed an inverse association between ALA and breast cancer risk. High dietary intakes of ALA were correlated with a reduced breast cancer risk (Franceschi et al., 1996). This study involved 2569 women with breast cancer and the result was supported by a cohort study conducted in the Netherlands (Voorrips et al., 2002). A significant inverse association was found between ALA content in breast adipose tissue and breast cancer risk (Klein et al., 2000 Maillard et al., 2002). Furthermore, ALA to LA ratio close to one was also significantly associated with lower breast cancer risk (Maillard et al., 2002). 

Tanaka M, Mukaiyama C et al (2002) Synthesis of optically pure gomisi lignans the total synthesis of (+)-schizandrin, (+)-gomisin A, and (+)-isoschizandrin in naturally occurring forms. J Org Chem 60 4339 -352... 

A number of biomimetic semi- or total syntheses using an oxidative coupling of a yatein or matairesinol-type intermediate to form stegane or isostegane lignans such as in Fig. (7) have been reported [35,87]. The major contributions will be reviewed in section 3.2.2. 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

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>. 

In the total syntheses of 2,5-diaryl-3,4-dimethyltetrahydrofuran lignans (-f )-fragrasin (-f)-galbelgin, (-f)-talau-midin, (—)-saucernetin, and (—)-verrucosin, a novel ring closure to tetrasubstituted tetrahydrofurans by intramolecular attack on a quinoid intermediate has been described <2007SL475>. 

More recent applications in target-oriented synthesis took advantage of the BVMO platform for the generation of enanhocomplementary lactones. In this context, butyrolactones represent appealing intermediates due to the facile availability of prochiral ketone substrates for enzyme-mediated desymmetrizations Scheme 21.7 indicates the potenhal in lignan total synthesis based on products obtained in a previous study [46]. The collechon of BVMOs exploited by our groups also allowed efficient access to various indole alkaloids via enanhocomplementary lactones obtained in the desymmetrizahon of fused bicycloketones [35]. 

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. 

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