Synthesis Of Lignans Research Articles

Selective Lewis Acid Catalyzed Transformation (γ-Butyrolactone versus Cyclopropane) of 2-Methoxy-4-benzyltetrahydrofuran Derivatives. Efficient Synthesis of Lignan Lactones

[reaction: see text]. A short synthesis of lactone lignans exploiting a three-component coupling strategy is presented using a new Lewis acid catalyzed ring-opening/cyclization reaction of 2-methoxytetrahydrofuran derivatives 4 leading to gamma-butyrolactones as a key step. By simply changing the reaction conditions, it was possible, from the same substrates 4, to obtain selectively cyclopropane derivatives.

An Approach to β‐Substituted γ‐Butyrolactones and Its Application to the Synthesis of Lignans.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Concise Enantioselective Synthesis of Furan Lignans (-)-Dihydrosesamin and (-)-Acuminatin and Furofuran Lignans (-)-Sesamin and (-)-Methyl Piperitol by Radical Cyclization of Epoxides

Enantioselective syntheses of furan lignans (-)-dihydrosesamin and (-)-acuminatin and furofuran lignans (-)-sesamin and (-)-methyl piperitol were achieved in up to only three steps in 43%, 42%, 63%, and 60% overall yield,respectively, with high optical purity through stereoselective intramolecular radical cyclization of suitably substituted epoxy olefinic ethers using bis(cyclopentadienyl)titanium(III) chloride as the radical initiator. The key intermediate, chiral epoxy alcohol 4, was prepared by the Sharpless kinetic resolution method. The titanium(III) initiator was prepared in situ from commercially available titanocene dichloride and activated zinc dust in tetrahydrofuran.

Radical-Mediated Synthesis of Racemic Deoxypodophyllotoxin and Related Lignans

An approach for the synthesis of lignans related to the podophyllotoxin family is reported. The key reaction is a highly diastereoselective iodoacetal cyclization under iodine atom transfer conditions followed by a homolytic aromatic substitution. The second aromatic ring is introduced at a later stage via addition of aryllithium to an aryl ketone. A novel and very mild method for the deoxygenation of the intermediate tertiary benzylic alcohols is described.

Synthesis and Structural Aspects of Some Intermediates in Furofuran Lignan Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Magnoshinin and Cyclogalgravin: Modified Stobbe Condensation Reaction

The development of new methods for lignan synthesis is reported. A recently reported method for the preparation of 1-aryl-1,2-dihydronaphthalenes is exploited to prepare magnoshinin, a naturally occurring lignan, and cyclogalgravin (3,4-dehydrogalbulin), a derivative of a natural lignan.

An Approach to β-Substituted γ-Butyrolactones and its Application to the Synthesis of Lignans

Copper-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with ArCH 2 MgCl afforded 4-arylmethyl-2-cyclopenten-1-ols regioselectively. Subsequent cleavage of the cyclopentene ring followed by functional group manipulation provided the key β-arylmethyl-γ-butyrolactones for the synthesis of lignans. In addition, synthesis of the rolipram lactone intermediate was accomplished.

Synthesis and structural aspects of some intermediates in furofuran lignan synthesis

The synthesis of some intermediates of furofuran lignans was accomplished by a chemical cyclisation reaction using N-ethylpiperidine hypophosphite and azobisisobutyronitrile. This reaction afforded the 5- exo-dig cyclic compound as the major product along with another isomeric cyclic compound which possess an endocyclic double bond. A brief discussion is presented to explain the formation of these isomeric cyclic compounds by a base-catalysed tautomerism mechanism. Some structural aspects are discussed based on nuclear magnetic resonance data.

Radical Annulation Route to the Synthesis of Lignans: an Account

AbstractFor Abstract see ChemInform Abstract in Full Text.

New chemo and chemo-enzymatic synthesis of β-benzyl-γ-butyrolactones

β-Benzyl-γ-butyrolactones, important intermediates for the synthesis of butyrolactone lignans, have been synthesized by a new route involving preparation of α-β-unsaturated formyl esters. The formyl esters can easily be converted into the desired butyrolactones either through chemical transformations or by enzymatic methods.

Different strategies for the chemical synthesis of lignans

This paper summarises the results of three projects. The first is concerned with developing general routes for the synthesis of lignans. In particular, two routes involving tandem conjugate addition reactions and Diels Alder reactions respectively that have been used to synthesise podophyllotoxin derivatives are described. The second project is concerned with the asymmetric synthesis of lignans and involves the application of these reactions, with the introduction of a menthyloxy group as a chiral auxiliary, to achieve the asymmetric synthesis of podophyllotoxin derivatives. The third project is concerned with the attempted biomimetic syntheses of podophyllotoxin derivatives using oxidative coupling reactions. Attention is focussed primarily on the use of hypervalent iodine reagents, which yield stegane and isostegane derivatives rather than podophyllotoxin derivatives. Other examples of biaryl coupling leading to stegane and isostegane derivatives are included, and other examples of lignan synthesis involving hypervalent iodine reagents are also described.

A Novel 1,3-Central-to-Axial Chirality Induction Approach to Cyclooctadiene Lignans

The catalytic asymmetric synthesis of an axially chiral biaryl, potentially useful intermediate in the synthesis of dibenzocyclooctadiene lignans, has been performed. The key step consisted of a diastereoselective Suzuki coupling between a chiral benzylic alcohol and a sterically hindered boronic ester. The 1,3-induction from the benzylic stereocenter to the biaryl axis proceeded with very good diastereoselectivity.

A new benzannulation reaction and its application in the multiple parallel synthesis of arylnaphthalene lignans

A new aromatic annulation reaction based on sequential Horner–Emmons and Claisen condensation reactions is described. The method is high yielding and provides a rapid entry to arylnaphthalenes. The lignan natural products justicidin B 1 , retrojusticidin B 2 , taiwanin C 3 , justicidin E 4 , chinensin 5 and retrochinensin 6 have all been synthesised in good overall yield using this protocol, demonstrating its potential in multiple parallel synthesis. The selective oxidation of diols 34– 36 to the corresponding retrolactones with barium manganate(VI) is also noteworthy.

Regioselectivity in oxidative cross-coupling of phenols. Application to the synthesis of dimeric neolignans

The problems of regioselectivity in oxidative coupling of phenols are outlined, and recent research on the application to the synthesis of lignans and neolignans is reviewed. Lignans and neolignans are dimers that are typically formed by oxidative coupling of propenyl phenols. The coupling of structurally different phenols (cross-coupling) is an extension of this synthesis. Recent results show that cross-coupling can be achieved if the phenols have compatible reactivities. The regioselectivity is often quite different in cross-coupling compared to dimerization. Coupling of phenols with widely different rates of oxidation is difficult but can be achieved if the concentration of the more reactive phenol can be kept low enough during the reaction, for instance by diffusion through a dialysis membrane.

Phenylcoumaran benzylic ether reductase, a prominent poplar xylem protein, is strongly associated with phenylpropanoid biosynthesis in lignifying cells.

It has previously been shown (D.R. Gang et al., 1999, J Biol Chem 274: 7516-7527) that the most abundant protein in the secondary xylem of poplar (Populus trichocarpa cv. 'Trichobel') is a phenylcoumaran benzylic ether reductase (PCBER), an enzyme involved in lignan synthesis. Here, the distribution and abundance of PCBER in poplar was studied at both the RNA and protein level. The cellular expression pattern was determined by immunolocalization of greenhouse-grown plants as well as of a field-grown poplar. Compared to other poplar tissues, PCBER is preferentially produced in the secondary xylem of stems and roots and is associated with the active growth period. The protein is present in all cells of the young differentiating xylem, corresponding to the zone of active phenylpropanoid metabolism and lignification. In addition, PCBER is located in young differentiating phloem fibers, in xylem ray parenchyma, and in xylem parenchyma cells at the growth-ring border. Essentially the same expression pattern was observed in poplars grown in greenhouses and in the field. The synthesis of PCBER in phenylpropanoid-synthesizing tissues was confirmed in a bending experiment. Induction of PCBER was observed in the pith of mechanically bent poplar stems, where phenylpropanoid metabolism is induced. These results indicate that the products of PCBER activity are synthesized mainly in lignifying tissues, suggesting a role in wood development.

3-Phenylselanylfuran-2(5 H)-one: a versatile building block in the synthesis of lignans. A new approach towards 3,4-dibenzyl γ-butyrolactones

Ready available 3-phenylselanylfuran-2(5 H)-one undergoes tandem conjugate addition-alkylation by organocopper reagents to afford, with good yields and diastereoselectivities, 3,4-disubstituted-3-phenylselanyl-γ-butyrolactones, which can be transformed into naturally occurring compounds, such as lignans.

ChemInform Abstract: Asymmetric Synthesis of Lignans Using Oxazolidinones as Chiral Auxiliaries.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric synthesis of lignans using oxazolidinones as chiral auxiliaries

A simple procedure for the asymmetric synthesis of lignans via chiral β-benzyl-γ-butyrolactones has been developed. The key benzylbutyrolactone intermediates were efficiently synthesized using a six-step procedure, starting from 3,4-(methylenedioxy)cinnamic acid. The key step in this sequence was a highly diastereoselective alkylation of an N-acyloxazolidinone enolate. The resulting β-benzyl-γ-butyrolactones were subsequently transformed into the benzylidene lignans gossypifan and savinin (hibalactone) via aldol condensation–dehydration reactions, and into the dibenzylbutyrolactone lignan 4′-demethylyatein, through alkylation. Oxidation of 4′-demethylyatein with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) afforded cis-and trans-benzylidenebenzylbutyrolactones, whereas oxidation with DDQ/TFA gave 4′-demethyl-deoxyisopodophyllotoxin. Keywords: lignans, synthesis, asymmetric, biosynthesis, oxidation, benzylbutyrolactones.

ChemInform Abstract: Enantioselective Entry into Benzoxabicyclo(2.2.1)heptyl Systems via Enzymatic Desymmetrization: Toward Chiral Building Blocks for Lignan Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective entry into benzoxabicyclo[2.2.1]heptyl systems via enzymatic desymmetrization: Toward chiral building blocks for lignan synthesis

The meso diacetate, 9, available in seven steps from piperonal, is efficiently desymmetrized with preferential cleavage of the R-arm-acetate under catalysis by porcine pancreatic lipase in 10% DMSO-phosphate buffer, pH 8. The resulting monoacetate 12, a potentially useful chiral building block for the synthesis of derivatives of the Podophyllum lignans, is obtained in good chemical yield (66–83%) and in high optical yield (95% ee) on a multigram scale.