Enterolactone

The most useful of the insertion processes is the intramolecular reactions that occur with high selectivity for the formation of five-membered ring products. The electrophilic nature of the process is suggested by C-H bond reactivity in competitive experiments (3°>20 >1°) [76, 77]. Asymmetric catalysis with Rh2(MPPIM)4 has been used to prepare a wide variety of lignans that include (-)-enterolactone (3) [8], as well as (R)-(-)-baclofen (2) [7],2-deoxyxylolactone (31) [80,81],and (S)-(+)-imperanane (32) [82].Enantioselectivities are 91-96%... 

DMA) and equol, while for lignans enterodiol and enterolactone should be used. 

Recently, some of the specific faecal bacteria involved in the metabolism of dietary isoflavonoids were isolated (Hur et al., 2000). They have been shown to selectively convert genistin and daidzin to their respective aglycones. One of the isolated bacteria, under anoxic conditions, was further shown to metabolise genistein and daidzein to their respective dihydroxy-genistein and dihydroxy-daidzein. In the case of lignans, enterodiol and enterolactone were shown to be excreted in vivo only in rats harbouring a gut microflora (Rowland et al, 1999). 

In our study we used serum enterolactone as a marker of bioavailability of phloem polyphenols from the wood matrix. As a result of the four-week... 

Substantial individual differences were observed in the response to study breads and the ranges of enterolactone concentration changes in the groups were as follows -54.5-60.0 nmol/1 (placebo), -26.2-101.3 nmol/1 (LP), -19.6-81.8 nmol/1 (HP). This was something that could have been expected as in several studies dietary factors have explained only 10% of the variation in serum enterolactone (Vanharanta et al, 2002b Kilkkinen et al., 2001). This gives further support to the major role of intestinal bacteria in the synthesis of enterolactone. Decreased concentrations of enterolactone may occur due to an increased fiber intake, which may shorten the retention time in the colon and lead to incomplete metabolism of plant lignans. Constipation was earlier shown to be associated with an increased level of serum enterolactone (Kilkkinen et al., 2001). 

H (1998) Time-resolved lluoroimmunoassay for plasma enterolactone, Analytical Biochemistry, 265, 208-15. 

JUNTUNEN K S, MAZUR W M, LIUKKONEN K H, UEHARA M, POUTANEN K S, ADLERCREUTZ H C T, MYKKANEN H M (2000) Consumption of wholemeal rye bread increases sermn concentrations and urinary excreation of enterolactone compared with consiunption of white wheat bread in healthy Fiimish men and women, British Journal of Nutrition, 84, 839 6. 

KILKKINEN A, STUMPF K, PIETINEN P, VALSTA L M, TAPANAINEN H, ADLERCREUTZ H (2001) Determinants of serum enterolactone concentration, American Journal of Clinical Nutrition 73, 1094-1100. 

STUMPF K, UEHARA M, NURMI T, ADLERCREUTZ H (2000) Changes in time-resolved fluoroimmunoassay of plasma enterolactone, Analytical Biochemistry, 284, 153-7. 

VANHARANTA M, VOUTILAINEN S, LAKKA T A, VAN DER LEE M, ADLERCREUTZ H, SALONEN J T (1999) Risk of acute coronary events according to serum concentrations of enterolactone a prospective population-based case-control study, The Lancet, 354, 2112-15. 

VANHARANTA M, MURSU J, VOUTILAINEN S, RISSANEN T H, NURMI T, SALONEN R, ADLERCREUTZ C H, SALONEN J T (2002a) Rye bread fortified with phloem increases serum enterolactone level, European Journal of Clinical Nutrition, in press. 

VANHARANTA M, VOUTILAINEN S, NURMI T, KAIKKONEN J, ROBERTS L J, MORROW J D, ADLERCREUTZ H, SALONEN J T (2002b) Association between low serum enterolactone and increased plasma F2-isoprostanes, a measure of lipid peroxidation, Atherosclerosis, 160,465-9. 

Asymmetric catalysis with Rh2(4Y-MPPIM)4 has been used to prepare a wide variety of lignans such as (+)-isodeoxypodophyllotoxin 70 (Equation (62))202,203 and (—)-enterolactone 71 (Equation (63)).194 The chemistry has also been utilized in the synthesis of (A)-(+)-imperanene 72 (Equation (64))197 and (R)-(—)-baclofen 73 (Equation (65)).198 Enantioselectivities of 91-96% ee have been obtained for a broad range of applications. 

Fig. 2.86. Chemical structures of the iosflavones daidzein, genistein, O-desmethylangolensin, equol, and the lignans enterolactone and enterodiol. Reprinted with permission from Z. Kuklenyik el al. [209].

Three cohort studies have been performed, one in European women, and two in oriental women eating a traditional soy-based diet. The study in European women, performed by Kardinaal et al. (1998), failed to show a correlation between change in forearm bone mineral density and urinary excretion of isoflavonoids. Excretion of enterolactone, a marker of intake of grain and berries, was found to correlate positively with bone mineral density. This may be explained with the difficulty of correlating bone mineral density -a multifactorial variable, influenced by diet only on long-term basis - with excretion of phytoestrogens that only quantify the last 24 to 48 hours of phytoestrogen intake. 

Demethylation of the methoxy groups in lactone 142 was achieved with BBr3 in dichloromethane. The reaction conditions were not optimized, and the yield of a-hydroxylated enterolactone 144 was low (15%). Several byproducts, such as both regioisomers of the mono-methylether, were obtained. 

Gut microflora metabolites may also be important. As discussed above, the mammalian lignan aglycones, enterodiol and enterolactone, are estrogenic, and equol is more estrogenic than its dietary precursor, the isoflavone daidzein. ... 

Johnsen, N.F., Hausner, H., Olsen, A., Tetens, L, Christensen, J., Knudsen, K.E., Overvad, K., and Tjonneland, A., Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women, J. Nutr., 134, 2691, 2004. 

Pietinen, P., Stumpf, K., Mannisto, S., Kataja, V., Uusitupa, M., and Adlercreutz, H., Serum enterolactone and risk of breast cancer a case-control study in eastern Finland, Cancer Epidemiol. Biomarkers Prev., 10, 339, 2001. 

Boccardo, F., Lunardi, G., Guglielmini, P., Parodi, M., Murialdo, R., Schettini, G., and Ruba-gotti. A., Serum enterolactone levels and the risk of breast cancer in women with palpable cysts, Eur. J. Cancer, 40, 84, 2004. 

Kilkkinen, A., Virtamo, J., Vartiainen, E., Sankila, R., Virtanen, M.J., Adlercreutz, H., and Pietinen, P., Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study, Int. J. Cancer, 108, 277, 2004. 

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