Lignans production

Thompson, L.U., Robb, P., Serraino, M., and Cheung, F. 1991. Mammalian lignan production from various foods. Nutr. Cancer 16, 43-52. 

A measure of the interest in the biological activity of these dibenzyl-butyrolactone lignans is evinced in the recent spate of publications dealing with the total synthesis of the natural optically active products. Again, the Stobbe condensation pathway (Scheme 9) has been usefully exploited for this purpose. In a series of papers, resolution of the intermediate hemisuccinate esters (433 by chiral bases has been described (54), as has asymmetric hydrogenation (55), and the optically active lignan products synthesized in the usual way (42 - 44 45). 

Thompson, L.U. Phytates in canola and rapeseed. Canola and Rapeseed - Production, Chemistry, Nutrition and Processing Technology, Shahidi, F. Ed. Van Nostrand Reinhold, New York, NY, 1990, pp. 173—192,. Thompson, L.U. Robb, R Serraino, M. Cheung, F. Mammalian lignan production from various foods. Nutr. Cancer 1991, 16, 43-52. 

Paska C, Innocent G, Kunvdri M, Laszlo, SzUagyi L (1999) Lignan production by Ipomoea cair-ica callus cultures. Phytochemistry 52 879-883... 

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%... 

HUTCHINS A M, SLAVIN J L and LAMPE I w (1995) Urinary isoflavonoid phytoestrogen and lignan excretion after consumption of fermented and imfermented soy products. JAm Diet Assoc 95, 545-51. 

ROWLAND I R, WISEMAN H, SANDERS T A, ADLERCREUTZ H and BOWEY E A (2000) luteriudividual variation in metabolism of soy isoflavones and lignans influence of habitual diet on equol production by the gut microflora. Nutr Cancer 36, 27-32. 

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. 

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. 

However, the enantiomeric control by DPs does not lead to the production of optically pure pinoresinol in plants, because the enantiomeric compositions of pinoresinol from various plant species vary widely and optically pure pinoresinol has not yet been isolated from plants [11,13, 53]. Downstream lignans in the lignan biosynthetic pathway, such as dibenzylbutyrolactone lignans including matairesinol, are optically pure [11, 13, 53]. These facts unequivocally indicate that not only was... 

Keywords a-Hydroxylated lignans Natural product synthesis Enantioselective hydrogenation Chiral building blocks Malic acid... 

Upon treatment of diastereoisomerically pure ketone (R)-16 with MeLi an 8 1 mixture of compounds ent-6 and ent-5 was obtained in 85% yield (Scheme 3). The synthetic isoschzandrin was in all respects identical to (+)-isoschizandrin (6). However, both, (-)-schizandrin ent-5) and (-)-isoschizandrin ent-6) have the opposite sign of optical rotation from those of the natural products, establishing the absolute configuration of the schizandra lignans. 

The enantiomers of the naturally occurring lignans, schizandrin (5) and isoschizandrin (6), have been prepared from oxazoline 10 in 11 steps with 0.7% and 5.5% overall yield, respectively. Although both natural products are accessible by this strategy, the reported synthetic approach is basically a route to isoschizandrin (6). Schizandrin (5) was obtained only as minor congener and a selective synthesis of 5 has not been accomplished by the authors. 

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