Lignan Lactones Research Articles

ChemInform Abstract: Syntheses of Pyrrolizidine Alkaloids and Lignan Lactone Glycoside Antitumor Agents and Their Biological Activities from the Standpoint of Diastereomer and Enantiomer

ChemInform Abstract: Syntheses of Pyrrolizidine Alkaloids and Lignan Lactone Glycoside Antitumor Agents and Their Biological Activities from the Standpoint of Diastereomer and Enantiomer

Oxidative Coupling of Lignans. IV. Monophenolic Oxidative Coupling

Oxidative coupling of the monophenolic monoester (6) gives an aryltetralin (12) which is a potential intermediate for the synthesis of clinically active monophenolic lignan lactones. In contrast, oxidative couplings of the monophenols (32) and (35), derived from matairesinol (29), give mixtures of diastereoisomeric cyclooctadiene lignans while 4′-demethyldeoxypodorhizon (26) does not cyclize . These results show that the degree of aromatic substitution in monophenolic diarylbutanes plays an important role in determining the outcome of oxidative coupling. An alternative synthesis of the lactone (57) from piperonal has been investigated.

Quinoline alkaloids and cytotoxic lignans from Haplophyllum tuberculatum

Three quinoline alkaloids and two lignan lactones were isolated from Haplophyllum tuberculatum. Physicochemical and spectral evidence established the structures of two of the alkaloids as a new quinoldione, 3-(1′,1′-dimethylallyl)-3-(3″,3″-dimethylallyl)-1,2,3,4-tetrahydro-2,4-quinoldione and the known 4-(3′,3′-dimethylallyloxy)-3-(3″,3″-dimethylallyl)-2(1H)-quinolone. The former was shown to undergo facile [3,3]-sigmatotropic transformation into the latter. The remaining compounds were identified as the known Polygamain, kusunokinin and 1-methyl-2-n-nonyl-4(1H)-quinolone.

ピロリジジンアルカロイドおよびリグナンラクトングリコシド制癌物質の合成と生理活性 エナンチオ，ジアステレオ異性体の観点より

This article describes the syntheses and the relationships between structure and antitumor activity of pyrrolizidine alkaloid (indicine N-oxide), lignan lactone glycoside (etoposide) and their related compounds from the standpoint of diastereomer and enantiomer.Total syntheses of indicine N-oxide, its diastereomer (intermedine N-oxide) and their enantiomers have been achieved in a totally stereospecific fashion through a sequence involving as the key steps (a) the enantioselective synthesis of retronecine and its enantiomer, (b) the enantioselective synthesis of (+) -trachelanthic acid and its enantiomer, and (c) a combination of each segments.Syntheses of all four possible diastereomers of etoposide and its aminoglycosidic analogues have been achieved via optical resolution of (±) -podophyllotoxin by glycosidation with D- and L-sugars.

Isolement, étude stéréochimique et synthèse biomimétique du stéganolide A, nouveau ligname bisbenzocyclooctadiénolactonique de [formula omitted

Resume Isolation of steganolide A from Steganotaenia araliacea (Apiaceae) -a new original bisbenzocyclooctadiene lignan lactone bearing an “ iso ” = M-6R biaryl junction (P,M, = Plus, Minus in terms of helicity nomenclature applied to axial chirality)- and short biomimetic total synthesis using intramolecular nonphenolic oxydative biaryl coupling as a key reaction were performed.

Les steganolides B et C, nouveaux lignanes analogues de l'episteganacine, isoles a partir de [formula omitted] hochst. - correlation 13C- 1H de la steganacine, en RMN bidimensionnelle -

Isolation from Steganotaenia araliacea Hochst. (Apiacaeae) and structure determination of Steganolides B and C -two new bisbenzocyclooctadlene lignan lactones having the same skeleton and bearing angeloyl and tigloyl benzylic substituants respectively- were performed with the help of high resolution 1H NMR at 500 MHz. An unambigous 13C assignement of the aliphatic carbones of the available steganacin congener was carried out in using 2D 1H 13C correlation and, skeleton conformation induced by the C 5 benzylic substitution in connection with 13C chemical shift and 1H vicinal coupling was established.

Studies on lignan lactone antitumor agents. I Synthesis of aminoglycosidic lignan variants related to podophyllotoxin.

D-(and L-)Aminoglycosidic variants of 4'-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4'-O-benzyloxycarbonyl- or 4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (8 or 22) with the corresponding aminosugar derivatives. Cyclic acetals of 1-O-(2-amino-2-deoxy- and 3-amino-3-deoxy-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxins (13 and 21) gave a significant survival time increase in mice with leukemia L-1210, and showed superior activity to VP-16-213 (etoposide, 5).

ChemInform Abstract: STEREOSELECTIVE REACTIONS. VIII. STEREOCHEMICAL REQUIREMENT FOR THE BENZYLIC OXIDATION OF LIGNAN LACTONE. A HIGHLY SELECTIVE SYNTHESIS OF THE ANTITUMOR LIGNAN LACTONE STEGANACIN BY THE OXIDATION OF STEGANE

AbstractDie Oxidation von Stegan (Ia) mit DDQ in Essigsäure liefert Steganacin (Ib) neben etwas Episteganacin (‐Ic).

High Pressure Liquid Chromato-Graphic Separation of Aryl-Naphthalide Lignan Lactones

Abstract A high-pressure liquid chromatographic system is described for the separation of few arylnaphthalide lignan lactones. An octadecyl-silica (Spherisorb 5 ODS) column was used with methanol/water (73/27 volume %) isocratic system as eluent. Both HPLC-fluorometry and HPLC-UV detection methods were employed. The present technique is compared with other instrumental methods developed earlier and its utility in chemotaxonomic and toxicologic studies is discussed.

Stereoselective reactions. VIII. Stereochemical requirement for the benzylic oxidation of lignan lactone. A highly selective synthesis of the antitumor lignan lactone steganacin by the oxidation of stegane.

A highly efficient synthesis of the antitumor steganin lignan steganacin (1) was accomplished. Bromination of stegane (7) with N-bromosuccinimide followed by treatment with aqueous tetrahydrofuran afforded steganol (3) in 85% yield. Acetylation of 3 gave 1 in 72% yield. Stegane (7) was also oxidized with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone in AcOH to give 1 directly in 10% yield. Stereochemical requirements for the benzylic oxidation of dibenzocyclooctadiene lignan lactones are discussed.

Sesquiterpene lactones from Centaurea glomerata

The investigation of the aerial parts of Centaurea glomerata afforded four new sesquiterpene lactones of the germacradienolide type and the lignan lactone arctigenin. Their structures were elucidated by spectroscopic methods.

Synthesis of deoxyisopodophyllotoxin and epiisopodophyllotoxin.

Cyclisation of the tandem conjugate addition products 1-3 by displacement of either the OH or SPh group provides a short efficient synthesis of lignan lactones including compounds of the clinically important podophyllotoxin series.

A new route to 1-phenylnaphthalenes by cycloaddition: a simple and selective synthesis of some naphthalene lignan lactones

2-(2-Dithianyl)benzhydrols ( 2 a-c) undergo facile cycloaddition reaction with maleic anhydride under thermal conditions to give 1-phenyl-naphthalenes ( 7 a-c) in one step. The naphthalenes ( 7 a-c) have been converted into the naphthalene lignan lactones, ( 9 a-c) and ( 10 a-c).

(+)-Calocedrin, a lignan dihydroanhydride from Calocedrus formosana

A novel lignan dihydroanhydride, (+)-calocedrin, was isolated from the wood of Calocedrus formosana. Its structure was determined to be trans-α-(3,4-methylenedioxybenzylidene)-β-(3,4-methylenedioxybenzyl)-γ-hydroxybutanolide by spectroscopic methods. Reduction of (+)-calocedrin resulted in an optically inactive lignan lactone, (±)-hibalactone.

Spectrofluorometric determination of the toxic constituents of Cleistanthus collinus.

Spectrofluorometric quantitation of a lignan lactone, diphyllin, and its glycosides cleistanthin A and cleistanthin B, the active principles of the poisonous plant Cleistanthus collinus, is reported for the first time. Thin layer chromatographic resolution of the components precedes the fluorometric measurements. The method is highly reproducible and sensitive to 0.1 microgram/mL for diphyllin and to 1 microgram/mL for cleistanthins A and B in ethanol. The technique is employed for the assay of several biospecimens of forensic and clinical importance.

Comparison of the feeding deterrent activity of some sesquiterpene lactones and a lignan lactone towards selected insect storage pests

Four sesquiterpene lactones isolated from Eurpatorium cannabinum, Homogyne alpina and Petasites albus (all Compositae), together with two of their adducts, as well as one lignan lactone of dibenzylbutanolide type from Libocedrus yateensis (Cupressaceae), were tested for their feeding deterrent activity against the adults of Sitophilus granarius and Tribolium confusum, as well as against the larvae of Tribolium confusum and Trogoderma granarium. The strongest deterrent activity against all species was exhibited by the lignan lactone yatein and the sesquiterpene spirolactone bakkenolide A. Both may be included to the class of very good insect feeding deterrents. The comparison presented here showed that the conjugated α-exomethylene moiety of the lactone ring was not the decisive factor for the deterrent activity in the investigated test model.

A Novel Synthetic Route to 1-Aryltetralin Lignan Lactone Via Intermolecular Cycloaddition with O-qu Inodimethane

Abstract Deoxyisosikkimotoxin 8 has been synthesized by an inter-molecular Diels-Alder approach.

Doctors in occupational medicine

It has been reported previously that the tetrahydropyranyl naphthtalenic lignan lactone L-702,539 is a potent nonredox, 5-lipoxygenase inhibitor that has the advantage that it can be dosed either as the lactone or as the corresponding nonactive hydroxy acid L-702,618 (opened lactone). Studies with hepatic microsomes from the rat, rhesus monkey, and human were undertaken in a phosphate buffer and suggested that the closure of the hydroxy acid L-702,618 to the lactone L-702,539 was an enzymatic process. The incubation of L-702,539 under oxidative conditions with these specific hepatic microsomes resulted in the formation of three significant metabolites (> 0.4 nmol/mg protein/hr) as determined by HPLC with UV detection. These metabolites were isolated from large microsomal incubations and were characterized by MS and NMR spectroscopy. Data showed that the lactone and tetrahydropyran portions of the molecule were both susceptible to hydroxylation, and the hydroxylated tetrahydropyran was further oxidized to the hydroxy acid. Analysis of plasma samples obtained from rat and rhesus monkeys following L-702,618 administration indicated that the in vivo metabolic pathway was similar to the one observed in vitro using hepatic microsomes. Studies conducted with microsomes from genetically engineered human cell lines expressing individual cytochrome P450s indicated that the isozyme responsible for the metabolism at the tetrahydropyran ring, was P4503A4. These findings were supported by studies conducted in human microsomes using an inhibitory P4503A4 antibody and troleandomycin, which is a potent P4503A inhibitor.

Neoisostegane, a new bisbenzocyclooctadiene lignan lactone from Steganotaeniaaraliacea hochst.

The structure of neoisostegane, 1, a new bisbenzocyclooctadiene lignan lactone was elucidated from its 1H and 13C NMR spectra and by chemical correlation with known steganes.

Synthesis of lignan lactones by conjugate addition of thioacetal carbanions to butenolide

The conjugate addition of carbanions dervied from arylbis(phenylthio)methanes to butenolide followed by trapping of the enolate anion so generated by a benzyl halide affords adducts (8) containing the basic lignan skeleton. Desulphurisation of these adducts by Raney nickel affords a short efficient synthesis of trans-dibenzylbutyrolactones and this route has been used to prepare enterolactone (9c) and an antitumour lignan (9b), derived from Bursera schlechtendalii. Treatment of the adducts (8) with heavy-metal salts induces cyclisation leading to arylnaphthalene lactones, including retrojusticidin B (13).