Assessing exposure to lignans and their metabolites in humans

Phytoestrogens occur naturally in plants and are structurally similar to mammalian estrogens. The lignans are a class of phytoestrogen and can be metabolized to the biologically active enterolignans, enterodiol, and enterolactone by a consortium of intestinal bacteria. Secoisolariciresinol diglucoside (SDG), a plant lignan, is metabolized to enterodiol and, subsequently, enterolactone. Matairesinol, another plant lignan, is metabolized to enterolactone. Other dietary enterolignan precursors include lariciresinol, pinoresinol, syringaresinol, arctigenin, and sesamin. Enterolignan exposure is determined in part by intake of these precursors, gut bacterial activity, and host conjugating enzyme activity. A single SDG dose results in enterolignan appearance in plasma 8-10 h later--a timeframe associated with colonic bacterial metabolism and absorption. Conjugation of enterolignans with sulfate and glucuronic acid occurs in the intestinal wall and liver, with the predominant conjugates being glucuronides. Controlled feeding studies have demonstrated dose-dependent urinary lignan excretion in response to flaxseed consumption (a source of SDG); however, even in the context of controlled studies, there is substantial interindividual variation in plasma concentrations and urinary excretion of enterolignans. The complex interaction between colonic environment and external and internal factors that modulate it likely contribute to this variation. Knowledge of this field, to date, indicates that understanding the sources of variation and measuring the relevant panel of compounds are important in order to use these measures effectively in evaluating the impact of lignans on human health.     

An approach to the biomimetic synthesis of aryltetralin lignans

The BF₃ catalysed cyclisation of 3-arylpropyl substituted quinone-methide ketals affords a mild, biomimetic route to aryltetralins. ¹H- and ¹³C-NMR spectra of the products are reported.     

An efficient method for the synthesis of lignans

An efficient approach for the synthesis of several types of lignans (dibenzylbutanediols, dibenzylbutanes, substituted tetrahydrofurans, aryldihydronaphthalenes, arylnaphthalenes, and aryltetralins) was developed. The regioselective oxidative coupling of ethyl ferulate was used as the key step.     

A versatile stereoselective synthesis of endo,exo-furofuranones: application to the enantioselective synthesis of furofuran lignans

A new stereoselective route to endo,exo-2,6-diarylfurofuranones has been developed using Mn(III)-mediated intramolecular cyclopropanation and C-H insertion reactions as key C-C bond-forming steps. Mn(III)-mediated oxidative cyclization of acetoacetate derivative 11 afforded 1-acetyl-4-aryl-3-oxabicyclo[3.1.0]hexan-2-one (12) with excellent diastereocontrol (d.r. 22:1). Subsequent Lewis acid-catalyzed opening of the activated cyclopropane ring present in 12 with benzylic alcohols then gave alpha-acetyl-gamma-butyrolactones 16 and 18-20, which reacted efficiently with in situ-generated TfN(3) to secure the key alpha-diazo-gamma-butyrolactones 22-25. Highly stereoselective rhodium-catalyzed C-H insertion reactions of diazolactones 22-25 completed the synthesis of endo,exo-2,6-diarylfurofuranones 26-29 in overall yields ranging from 41 to 48% from 1-phenylallyl alcohol (+/-)-10. The approach developed for the furofuranones 26-29 was then applied to the asymmetric syntheses of four furofuran lignans, (+)-xanthoxylol (1), (+)-methylxanthoxylol (2), (+)-epipinoresinol (3), and (+)-epieudesmin (4), starting from enantiomerically enriched 1-arylallyl alcohol (S)-31.     

Asymmetric synthesis of the dibenzocyclooctadiene lignans interiotherin a and gomisin R

[structure: see text] Asymmetric total syntheses of the dibenzocyclooctadiene lignans interiotherin A and angeloylgomisin R are reported. The syntheses were based on an atropdiastereoselective, copper-promoted biaryl coupling reaction, a diastereoselective hydroboration/Suzuki-Miyaura coupling reaction sequence, and an asymmetric boron-mediated tiglylation of an aryl aldehyde precursor.     

An Ireland-Claisen approach to lignans: synthesis of the putative structure of 5-epi-eupomatilone-6

A novel Ireland-Claisen approach to the putative structure of eupomatilone-6 is described. The rearrangement established the C3 and C4 stereocenters and concomitantly generated a vinyl epoxide. The C5 oxygen was installed by cyclization of the pentenoic acid carboxyl group onto the vinyl epoxide in an S(N)2' fashion to afford the C5-epi stereochemistry. The natural C5 stereochemistry was accessed via a substrate directed dihydroxylation.     

Asymmetric synthesis of homochiral dibenzylbutyrolactone lignans by conjugate addition to a chiral butenolide

Addition of sulphur stabilised carbanions to a chiral non-racemic butenolide followed by reaction with an aromatic aldehyde affords a short synthesis of homochiral dibenzylbutyrolactone derivatives. Desulphurisation of the first formed adducts proceeds in almost quantitative yield to afford the parent lignan.     

The first total synthesis of a highly branched arabinofuranosyl hexasaccharide found at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan

[reaction--see text] The first total synthesis of the arabinofuranosyl hexasaccharide present at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan is reported. The oligosaccharide was prepared as its methyl glycoside via a route that is both highly efficient and convergent. Addition of two beta-D-arabinofuranosyl residues simultaneously in high yield and with excellent stereocontrol was the key step of the synthesis.     

Chemical studies on antioxidant mechanisms and free radical scavenging properties of lignans

The antioxidant activity, in terms of radical scavenging capacity, of altogether 15 different lignans was measured by monitoring the scavenging of the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The effect of differences in skeletal arrangement or the degree of oxidation of the lignans was investigated in a structure-activity relationship study. A large variety in the radical scavenging capacities of the different lignans was observed and related to some structural features. Lignans with catechol (3,4-dihydroxyphenyl) moieties exhibited the highest radical scavenging capacity, while the corresponding guaiacyl (3-methoxy-4-hydroxyphenyl) lignans showed a slightly weaker scavenging capacity. In addition, the butanediol structure was found to enhance the activity, whereas a higher degree of oxidation at the benzylic positions decreased the activity. Additionally, the readily available lignans (-)-secoisolariciresinol, a mixture of hydroxymatairesinol epimers and (-)-matairesinol were studied in more detail, including kinetic measurements and identification of oxidation products in the reactions with DPPH and ABAP (2,2-azobis(2-methylpropionamidine) dihydrochloride. The identification of reaction products, by GC-MS, HPLC-MS and NMR spectroscopy, showed that dimerisation of the two aromatic moieties was the major radical termination reaction. Also, the formation of adducts was a predominant reaction in the experiments with ABAP. The kinetic data obtained from the reactions between the lignans and DPPH indicated a complex reaction mechanism.     

化学命题应注意科学性

近来,笔者翻阅了许多化学参考书,发现一个不容忽视的问题,即一些习题凭空编造、命题不严,甚至出现严重的科学性错误。现列举几例说明如下。人民教育出版社(90年第4次印刷)的高中化学课外习题集》上册P—254,26题:“4.35克二氧化锰与25毫升12摩尔/升盐酸混和,加热充分反应后,冷却,向容器中加入足。     

Stereoselective total synthesis of furofuran lignans through dianion aldol condensation

Highly stereoselective total synthesis of (+)-eudesmin, (+)-yangambin, (−)-eudesmin, and (−)-yangambin is described. This method is useful to generate the core skeleton of furofuran rings utilizing modification of Evans asymmetric aldol condensation.     

In vivo determination of amino acid bioavailability in humans and model animals

Because the digestion of many dietary proteins is incomplete, and because there is a continuous (but variable) entry into the intestinal lumen of endogenous protein and amino acid nitrogen that is also subject to digestion, the fluxes of nitrogen, amino acids, and protein in the gut exhibit a rather complicated pattern. Methods to distinguish and quantitate the endogenous and dietary components of nitrogen and amino acids in ileal chyme or feces include the use of a protein-free diet, the enzyme-hydrolyzed protein method, different levels of protein intake, multiple regression methods, and stable-isotope labelling of endogenous or exogenous amino acids. Assessment of bioavailability can be made, with varying degrees of difficulty, in man directly but, for routine evaluation of foods, the use of model animals is attractive for several reasons, the main ones being cost and time. Various animals and birds have been proposed as models for man but, in determining their suitability as a model, their physiological, enzymological, and microbiological differences must be considered. Fecal or ileal digestibility measurements, as well as apparent and true nitrogen and amino acid digestibility measurements, have very different nutritional significance and can, thus, be used for different objectives. Measurements at the ileal level are critical for determining amino acid losses of both dietary and endogenous origin, whereas measurements at the fecal level are critical in assessing whole-body nitrogen losses. A complementary and still unresolved aspect is to take into account the recycling of intestinal nitrogen and bacterial amino acids to the body.     

Acute toxicity and rapid excretion in urine of tetramethylarsonium salts found in some marine animals

Acute toxicity in mice, and excretion in their urine, of tetramethylarsonium salts which are arsenic compounds found in some marine animals, were examined using synthetic tetramethylarsonium iodide. The oral, intraperitoneal and intravenous LD₅₀ values of tetramethylarsonium iodide [(CH₃)₄As⁺I^?] were determined to be 890, 175 and 82 mg kg^?1, respectively. When sublethal doses of tetramethylarsonium iodide were orally administered to mice, 53–58% of the arsenic administered was recovered in urine after 6 h and 65–81% after 72 h. High-performance liquid chromatography–inductively coupled plasma (HPLC–ICP) and fast atom bombardment mass spectrometric (FAB MS) analyses revealed that a tetramethylarsonium salt was the only arsenic compound excreted in urine. These results suggested that the major part of orally administered tetramethylarsonium iodide was absorbed from the gastrointestinal tract in mice and then rapidly excreted in urine without biotransformation.     

An efficient asymmetric synthesis of furofuran lignans: (+)-sesamin and (−)-sesamin

An efficient synthesis of (+)-sesamin 1a and (−)-sesamin 1b is described. The key reactions include highly stereoselective aldol condensation of piperonal 7 with the dianion of chiral oxazolidinone 8, followed by intramolecular ring cyclization of aldol product 11 in high yield.     

Highly regioselective lactone formation catalyzed by ruthenium complexes. An application to synthesis of arylnaphthalene lignans

Ruthenium catalyzed hydrogenation of cyclic anhydrides and dehydrogenation of diols have been successfully applied to the highly regioselective synthesis of arylnaphthalene lignans.     

Comparison between biokinetics of inhaled plutonium nitrate and gadolinium oxide in humans and animals

Due to the paucity of human data after inhalation of different chemical forms of radionuclides, the implications for human exposure are often based on animal studies. This paper describes biokinetic studies of plutonium nitrate and gadolinium oxide in human volunteers and rats. The results, together with information from other studies with radionuclides, suggests that animal studies can be used with advantage for assessing the biokinetic behavior in humans, and for providing guidance on the assessment of intake and optimal monitoring regimens.