Lactone lignans

Two different classes of optically active a-hydroxylated lignans have been prepared from sugars by Yamauchi and co-workers lactone lignans [47, 48] and tetrahydrofuran lignans [49, 50]. In both cases, only model compounds were synthesized, such as lactone lignan 55 (Scheme 13), as a result of the synthetic strategy. The key intermediate for the synthesis of lactone lignan... 

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. 

The stereoselective introduction of both benzyl groups simultaneously in one step seemed to be particularly attractive for a short synthesis of a- hy-droxylated lactone lignans from malic acid (99). Such a simultaneous double alkylation requires the formation of a chiral l,3-diene-l,4-diolate, which was not known. On the other hand, achiral 1,3-diene-1,4-diolates (di-enolates) have been previously prepared by Garrett et al. [58] and subsequently employed for the synthesis of racemic lignans by Snieckus [59] and Pohmakotr [60]. With knowledge of the synthesis and reactivity of di-enolates, we planned to prepare chiral di-enolates from dioxolanones and to alkylate these di-enolates in a stereocontrolled manner (Scheme 22). For the development of the described double deprotonation/alkylation strategy, tert-hutyl... 

Hydrogenolysis of the benzylether of lactone 141 (H2, 10% Pd/C) quantitatively afforded (-)-wikstromol ent-3). The overall yield of ent-3 from diisopropyl malate 107 over six steps was 30% [62]. This strategy for the construction of optically-active lactone lignans provided a short and stereoselective synthesis with comparably good overall yield. 

The inhibition of proliferation of several cancer cells was investigated with the compounds shown in Fig. 8. One of these lignans, compound 143, was active, having an IC50 of ca. 35 fxmol/1 against HT 29 colon cancer cells [75] and others [76]. This result was in agreement with previously observed cytotoxicities of a-unfunctionalized lactone lignans [77]. 

Our strategy for the synthesis of a-hydroxylated lactone lignans might be extended to the general synthesis of a-hydroxylated lignans, when either of the alkylation steps is changed to an aldol addition. For example, berchemol... 

Some approaches to the stereoselective synthesis of a-hydroxylated lactone lignans have been reported [59,60]. As a short and efficient example, the synthesis of a dibenzylbutyrolactone lignan wikstromol from two diastereo-selective alkylations of malic acid (+) has recently been reported [61]. In order to get high stereoselectivity, isoPr malate was chosen for the synthesis of (+)-wikstromol its formation in six steps with a 20% overall yield is shown in Fig. 10. 

Kamil, W.M. and Dewick, P.M. (1986b) Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry, 25, 2093 102. 

Main components Bitter constituents like the sesquiterpene lactone cnicin (0.2-0.7%) and lactonic lignans [31 [ as well as polyacetylenes and traces of essential oil. 

Aberham A, Cicek SS, Schneider P, Stuppner H (2010) Analysis of sesquiterpene lactones, lignans, and flavonoids in wormwood (Artemisia absinthium 1.) using high-performance liquid chromatography (HPLC)-mass spectrometry, reversed phase HPLC, and HPLC-solid phase extraction-nuclear magnetic resonance. J Agric Food Chem 58 10817-10823... 

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