Lignans transformations

Mabrok HB, Klopfleisch R, Ghanem KZ, Clavel T, Blaut M, Loh G. Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer. Carcinogenesis. 2012 33 203-208. 

The strategy was chosen because compound 57 is readily prepared from 58 and is easily transformed to 56 by a-alkylation followed by reduction of the lactone moiety. Additionally, both cis- and frans-lactone lignans can be synthesized by one common intermediate. 

Partially hydrogenated quinoline cores are also present in some important bioactive compounds. For example, the 4-aza-analogs of Podophyllotoxin, a plant lignan that inhibits microtubule assembly, revealed to be more potent and less toxic anticancer agents. In 2006, Ji s group reported a green multicomponent approach to a new series of these derivatives, consisting of the reaction of either tetronic acid or 1,3-indanedione with various aldehydes and substituted anilines in water under microwave irradiation conditions (Scheme 26) [107]. For this efficient and eco-friendly transformation, the authors proposed a mechanism quite similar to the one that was postulated for the synthesis of tetrahydroquinolines in the precedent section. 

Wang, L.Q., Meselhy, M.R., Li, Y., Qin, G.W., and Hattori, M., Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone, Chem. Pharm. Bull, 48, 1606, 2000. 

Highly substituted 2,3-dihydrofurans 44 (Scheme 1.3.18) would make particularly interesting starting materials for the asymmetric synthesis of tetrahydrofu-rans, structural motifs which can be found in many important natural products, including polyether antibiotics, lignans, and nucleosides [30]. Not only the activated double bond but also the vinylic silyl group of 44 should allow useful synthetic transformations. 

The 1,4-diketone (30) has been cyclized with polyphosphoric acid to give the 2,5-diarylfuran (31), which was later transformed into lignan intermediates (79T861). 

Coniferin (the (3-D-glucoside of coniferyl alcohol) is accumulated prior to lignin formation as well as in lignan-s)mthesizing cell cultures (e.g. Berlin et al, 1986 Van Uden et al., 1991 Smollny et al, 1998). Coniferin and lignan contents were found to be inversely correlated in cell cultures. However, there is no direct proof for a transformation of stored coniferin to lignans. Feeding of coniferin resulted in an enhanced podophyllotoxin accumulation in cell cultures of Podophyllum hexandrum (Van Uden et al, 1990). 

A wide series of oxidants, spanning from TiCLj to iodine, has been used in the oxidative homocoupling of chiral 3-arylpropionic acid derivatives aimed at the preparation of lignans. The /f,/f-selectivity in the reactivity of 34 has been explained by a radical coupling mechanism (equation 20). The initially formed lithium (Z)-enolate may transform into the titanium enolate 35, which undergoes oxidation to the radical intermediate 36 via a single electron transfer process. The iyw-Z-type radicals 36 couple each other at the less hindered S-side si face) to give the R,/f-isomers 37 stereoselectively. 

Figure 9. Sesame seed lignans (sesamin and sesamolin) and their acid-catalyzed transformation products generated during bleaching.

A convenient route to lignans of this class is apparent from the known transformation of the phenylpropiolic acid to the anhydride of phenylnaphthalene-2,3-dicarboxylic acid by the action of acetic anhydride (Scheme 19). This reaction was discovered about a century ago (94) the interesting early history has been briefly reviewed (95) and a wide generality of the reaction demonstrated (96). It is particularly useful for products bearing identical substituents in rings A and C. Thus, it has been long known that 3,4-methylenedioxyphenylpropiolic acid (1011 on... 

Oxidative cleavage of the furo-furan unit of lignans delivers hydroxy ketones. However, the successful transformation must be carried out at -20° and under high dilution. 

LH Xie, T Akao, K Hamasaki, T Deyama, M Hatton. Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and Isolation of enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chem Pharm Bull 51 508-515, 2003. 

M Nose, T Eujimoto, T Takeda, S Nishibe, Y Ogihara. Structural transformation of lignan compounds in rat gastrointestinal tract. Planta Medica 58 520-523, 1992. 

Tetradecanoylphorbol 13-acetate (TPA) and other diterpene esters from the plant family Euphorbiaceae are well-known as tumor-promotion agents [85]. Thus, inhibition of the biological effects induced by TPA has been considered as a promising strategy [68]. To date, two short-term cell-based in vitro bioassays using TPA as a tumor-promoter have been developed to evaluate the potential cancer chemopreventive activities of several lignans isolated from Hernandia species, namely, inhibition of Epstein-Barr virus early antigen activation [6] and the inhibition of the transformation of JB6 mouse epidermal cells [7]. 

Yamauchi et al. completed an ex-chiral pool synthesis of a samin-type lignan, Scheme (38) [102]. The diprotected tetraol 230 was obtained from Z-glutammic acid by a 15 step procedure in 7-8% overall yield [103]. The diprotected tetraol 230 was treated with boron trifluoride diethyl etherate in dichloromethane to give the tetrahydrofuran 231 in 84%-87% yield. After deprotection with tetrabutylammonium fluoride, the resulting diol was oxidized by dihydridotetrakis(triphenylphospine)ruthenium(II) to provide two lactones 232 and 233 in a ratio of 2 1. Lactone 232 was transformed in samin-type lignan 234 by diisobutylaluminium hydride reduction in 70% yield. 

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