Lignans from Piper cubeba

From the hot petrol extract of Piper cubeba ftuits, six lignans were isolated. Two of these, which have been obtained from a natural source for the first time, have been characterized as (2R,3R)-2-(3″,4″,5″-trimethoxybenzyl)-3-(3′,4′-methylenedioxybenzyl)-1,4-butanediol [(?)-dihydroclusin] and (3R,4R)-3,4-bis-(3,4,5-trimethoxybenzyl)tetra-hydro-2-furanol [(?)-cubebinin]. (?)Cubebin, (?)-hinokinin, (?)-clusin and (?)-dihydrocubebin were also found in this plant. Only (?)-cubebin has been reported so far from this source.     

Synthesis of Analogs of Optically Active α-Ionylideneacetic Acid

The Wittig reaction of (?)-α-ionone (VIa) with carbethoxymethylenetriphenylphosphorane afforded (?)-ethyl α-ionylideneacetate (VIIa). tert-Butyl chromate oxidation of the above ester (VIIa) gave (?)-ethyl 4′-keto-α-ionylideneacetate (VIlla). Selenium dioxide oxidation of (?)-α-ionone (IVa) in ethanol afforded (?)-1′-hydroxy-α-ionone (X), which reacted with car-bethoxymethylenetriphenylphosphorane to give (?)-ethyl 1′-hydroxy-α-ionylideneacetate (XI). tert-Butyl chromate oxidation of the hydroxy-ester (XI) gave (?)-ethyl abscisate (XII) and ethyl 3′-keto-β-ionylideneacetate (XIII). The sensitized photooxidation of ethyl dehydro-β-ionylideneacetate (XVI) using chlorophyll was attempted.     

Biotransformations. XIX. Reduction of some terpenic ketones by means of immobilized cells of rhodotorula mucilaginosa

Reduction of (?)-menthone ((?)- 1 ), (+)-(R)-methyl-α-campholenone ((+)- 2 ), (+)-carvone ((+)- 3 ), and eucarvone ( 4 ) was carried out by means of cells of the Rhodotorula mucilaginosa species immobilized in polyacrylamide gel. Alcohols with the (S)-configuration, (+)-neomenthol ((+)- 1a ), (+)-(R)-methyl-α-campholenol ((+)- 2a ), (?)-neoisodihydrocarveol ((?)- 3a ), dihydroeucarveol ((?)- 4a ), and small amounts of (?)-dihydroeucarvone ((?)- 5 ), were obtained. The cells of R. mucilaginosa maintained after this reaction ability to reduce standard acetophenone to (?)- 1 -phenyl- 1 -ethanol.     

The absolute configuration of the enantiomers of 6-chloro-9-(4′-diethylamino-1′-methylbutyl)-amino-2-methoxyacridine (quinacrine)

Absolute configurations have been assigned to the enantiomers of the antimalarial drug quinacrine dihydrochloride. Condensation of (?)-(R)-4-amino-1-diethylaminopentane (from L -glutamic acid) with 6,9-dichloro-2-methoxyacridine gave (?)-(R)-6-chloro-9-(4′-diethylamino-1′-methylbutyl) amino-2-methoxyacridine [(?)-(R)-quinacrine] while (+)?(S)-quinacrine was obtained from the enantiomeric diamine.     

Synthesis of (−)-Methyl Shikimate via Enzymatic Resolution of (1S*, 4R*, 5R*)-4-Hydroxy-6-oxabicyclo[3.2.1]oct-2-en-7-one

The synthesis of methyl (?)-shikimate [(?)-2] was achieved via lipase-catalyzed optical resolution of (1S^*,4R^*,5R^*)-4-hydroxy-6-oxabicyclo[3.2.1]oct-2-en-7-one (3). Transesterification of (±)-3 and vinyl acetate with lipase MY and subsequent hydrolysis gave optically pure (?)-3. This compound was converted to (?)-2 in two steps.     

Isolation and synthesis of trans- and cis-(−)-clovamides and their deoxy analogues from the bark of Dalbergia melanoxylon

N-(3′,4′-Dihydroxy-trans-cinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine [(?)-clovamide], the major phenolic metabolite (0.1%) in the bark of Dalbergia melanoxylon, is associated with minor proportions of its cis-isomer, and similar pairs of geometrical isomers of their deoxy analogues N-(4′-hydroxycinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine and N-(4′-hydroxycinnamoyl)-3-(4-hydroxyphenyl)-L-alanine. (?)-Trans-clovamide is synthesized by direct condensation of the acid chloride of caffeic acid with L-DOPA. Diagnostic CD spectra of these compounds and ¹³C spectra of (?)-trans- and (?)-cis-clovamides are recorded.     

A benzopyrroloisoquinoline alkaloid from Ficus fistulosa

A new benzopyrroloisoquinoline alkaloid, fistulosine (1), was isolated from the stem-bark of Ficus fistulosa (Moraceae) collected in Singapore, along with three known phenanthroindolizidine alkaloids, (?)-13aα-antofine (2), (?)-14β-hydroxyantofine (3) and (?)-13aα-secoantofine (4). (?)-13aα-Antofine (2) accounted for the antifungal activity against Aspergillus fumigatus and Candida albicans originally observed in the crude alkaloid extract.     

Synthesis of (+)-(R)- and (−)-(S)-5-hydroxy-2-methyl-2-dipropylaminotetralin: Effects on rat hippocampal output of 5-HT, 5-HIAA,and DOPAC as determined by in vivo microdialysis

Racemic 5-methoxy-2-methyl-2-dipropylaminotetralin ( 3 ) has been prepared by a short synthetic route, in which the N,N-dipropyliminium perchlorate of 5-methoxy-2-tetralone ( 4 ) is a key intermediate. Racemic 3 was resolved by crystallization of the corresponding diastereomeric di-p-toluoyltartrates. The enantiomeric excess (%ee) of the phenolic derivatives of (+)-(R)- and (?)-(S)-3 [(+)-(R)- and (?)-(S)-2] was determined by ¹HNMR spectroscopic analysis of the corresponding diastereomeric (?)-(R)-1,1′-binaphthyl-2,2′-diylphosphoric acid salts utilizing ¹³C satellites. X-ray crystallography established the absolute configuration of (?)-(S)-2 · HCl. The enantiomers of 2 were tested for hippocampal output of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, and dihydroxyphenylacetic acid in rats by use of in vivo microdialysis. The (?)-(S)-enantiomer appeared to affect 5-HT-turnover, whereas (+)-(R)- 2 was inactive. Results obtained provide support for the previously reported hypothesis that the inactivity of (?)-(S)- 2 at central DA receptors is caused by the steric bulk of the C(2)-methyl group. This makes it possible to define a “DA D2 receptor essential volume.” © 1993 Wiley-Liss, Inc.     

Stereoselective distribution of hydroxychloroquine in the rabbit following single and multiple oral doses of the racemate and the separate enantiomers

Hydroxychloroquine (HCQ) stereoselective distribution was investigated in rabbits after 20 mg/kg po of racemic-HCQ (rac-HCQ) and 20 mg/kg po of each enantiomer, 97% pure (?)-(R)-HCQ and 99% pure (+)-(S)-HCQ. Concentrations were 4 to 6 times higher in whole blood than in plasma. Melanin did not affect plasma and whole blood levels since concentrations did not differ between pigmented and nonpigmented animals. After single and multiple doses of the separate enantiomers, only 5–10% of the antipode could be measured, in blood or plasma. Therefore, there was no significant interconversion from one enantiomer into the other. Following rac-HCQ, plasma (+)-(S)-levels always surpassed (?)-(R)-ones while in whole blood, (?)-(R)-HCQ concentrations were always the highest. When the enantiomers were administered separately, blood concentrations achieved after (?)-(R)-HCQ were higher, especially after multiple doses. These observations suggest that (?)-(R)-HCQ is preferentially concentrated by cellular components of blood. This enantioselective distribution of HCQ could be secondary to a stereoselective protein binding to plasma proteins, although a more specific binding of (?)-(R)-HCQ to blood cells cannot be ruled out. Since in whole blood (?)-(R)-HCQ is retained in cellular components, metabolism would favour the more available (+)-(S)-enantiomer. © 1994 Wiley-Liss, Inc.     

Pyruvate Decarboxylase Catalysed Formation of Terpenoid α-hydroxy Ketones

Enzyme extracts of the wild type yeast Zygosaccharomyces bisporus were applied for the pyruvate decarboxylase catalysed condensation of pyruvate and (R)-(+)-and (S)-(?)-perillyl aldehyde, (±)-citronellal, neral, geranial or (R)-(?)-myrtenal to form novel α-hydroxy ketones. Best yields were obtained when the transformation medium contained 25% (v/v) of the cosolvent N,N-dimethylformamide. Conversion of (R)-(+)-perillyl aldehyde to (1R)-1-hydroxy-1-[(4’R)-4’-isopropenyl-1-cyclohexen-1-yl]-2-propanone proceeded highly stereospecifically (>99% de), whereas the stereoselectivity was somewhat less in the transformation of (S)-(?)-perillyl aldehyde (58% de) and (R)-(?)-myrtenal (92% de). All of the new compounds imparted characteristic odour impressions as determined by means of GC-olfactometry.     

Synthesis and Antimicrobial Activity of Chiral cis-Cycloheximide Isomers

Such (+)- and (?)-cis-cycloheximide isomers as isocyclohcximide (1a, 1b), α-epiisocycloheximide (2a, 2b) and neocycloheximide (3a, 3b) were synthesized by aldol condensation of (?)-(2R, 4R)- and (+)-(2S, 4S)-cis-2,4-dimethyl-1-cyclohexanone (5a, 5b). obtained by microbial resolution, with 4-(2-oxoethyl)-2,6-piperidinedione (7). The absolute configuration of the (?)-cis-ketone 5a was confirmed by chemical correlation with natural (2S, 4S, 6S, αR)-cycloheximide (4). The newly synthesized isomer, (?)-α-epiisocycloheximide (2b), showed strong antimicrobial activity against S. cerevisiae andP. oryzae close to that of natural cycloheximide (4).     

Relative configuration of thioridazine enantiomers

The relative configuration of the enantiomers of thioridazine was defined to explore the stereochemistry associated with the selective binding of (?)-thioridazine to dopamine D-1 receptors and (+)-thioridazine to D-2 receptors. Using a seven-step stereoconservative synthesis, (?)-(S)-2-piperidinecarboxylic acid was converted to (?)-(S*)-2-(2-chloroethyl)-1-methylpiperidine, a literature (?)-thioridazine synthetic precursor. Accordingly, (?)- and (+)-thioridazine are the (S)- and (R)-enantiomers, respectively.     

Neolignans from Virola carinata

The wood of Virola carinata (Benth.) Warb. contains besides the known neolignans (+)-guaiacin and (?)-galcatin, (?)-isootobaphenol [(2R,3S,4S)-4-guaiacyl-2,3-dimethyl-6,7-methylenedioxytetralin], in addition to 7,4′-dimethoxyflavanone.     

Synthesis and plant growth inhibitory activities of (+)- and (−)-(2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid

Chiral (+)- and (?)-enantiomers of (2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid have been synthesized from the chiral epoxy alcohols (+)- and (?)-1′,2′-dihydro-1′,2′-epoxy-β-ionone, which were prepared by Katsuki-Sharpless' asymmetric epoxidation of β-cyclogeraniol. The (+)-enantiomer showed strong inhibitory activity in a rice seedling and lettuce germination assay, whereas the (?)-enantiomer was 10³-times less active.     

Eudesmane alcohols from jasonia glutinosa

Three new sesquiterpene alcohols have been isolated from Jasonia glutinosa. Their structures were elucidated by spectroscopic methods and chemical correlations as (?)-[11R]-4α,14-epoxyeudesm-11,12-diol, (?)-[11R]-eudesm-4(14)-en-5β,11,12-triol and (+)-[11R]-eudesm-4(14)-en-5α,11,12-triol and they are called α-epoxy kudtdiol, 5-epi-kudtriol and kudtriol respectively.     

(−)-Cryptocaryalactone and (−)-deacetylcryptocaryalactone-germination inhibitors from Cryptocarya moschata seeds

(?)-Cryptocaryalactone (6-[2-acetoxy-4-phenyl-3-butenyl]-5,6-dihydro-2-pyranone) and (?)-deacetylcryptocaryalactone (6-[2-hydroxy-4-phenyl-3-butenyl]-5,6-dihydro-2-pyranone) isolated from Cryptocarya moschata seeds are natural germination inhibitors. Applied at 0.004 M, the second compound completely arrested germination of velvetleaf (Abutilon theophrasti) and decreased the germination rate of soybeans, but did not appear to affect corn. The first compound was not as effective; 0.004 M reduced velvetleaf germination 50%.     

Structure and functions of γ-dodecalactone isolated from Antrodia camphorata for NK cell activation

The preserved fungal species Antrodia camphorata has diverse health-promoting effects and has been popularly used in East Asia as a traditional herb. We isolated a volatile compound from the culture medium of A. camphorata and identified it as γ-dodecalactone (γ-DDL). Cytomic screening for immune-modulating activity revealed that γ-DDL can activate human NK cells to express the early activation marker CD69. Further experiments showed that γ-DDL not only can induce NK cells to express CD69 but also stimulate NK cells to secrete cytotoxic molecules (FasL and granzyme B) and Th1 cytokines (TNF-α and INF-γ).Measuring the distribution of γ-DDL in the subcellular compartments of NK cells revealed that γ-DDL has been converted to 4-hydroxydodecanoic acid (an acyclic isomer of γ-DDL) in a time-dependent manner in the cytoplasm.Synthetic (R,S)-4-hydroxydodecanoic acid activated NK cells to express CD69 mRNA within 10 min, in contrast to γ-DDL, which activated NK cells to express CD69 within 50 min. This faster activation suggests that γ-DDL has converted to 4-hydroxydodecanoic acid and to stimulate the NK cells to express CD69.Optically pure (R)-(+)-4-hydroxydodecanoic acid and (S)-(?)-4-hydroxydodecanoic acid were obtained via: (1) synthesis of its diastereomeric esters of (R,S)-4-hydroxydodecanoic (R)-(?)-2-phenylpropionate; (2) separation of diastereomers via preparative HPLC, and (3) subsequent hydrolysis of the obtained optical pure ester of (R)-(+)-4-hydroxydodecanoic acid (R)-(?)-2-phenylpropionate and (R)-(?)-4-hydroxydodecanoic acid (R)-(?)-2-phenylpropionate, respectively. Further assays of NK cells activation using each enantiomer showed that only the (R)-(+)-4-hydroxydodecanoic acid can activate NK cells.     

Biosynthesis of pisatin: Experiments with enantiomeric precursors

Feeding experiments in cupric chloride-treated Pisum sativum pods and seedlings have demonstrated the preferential incorporation of (+)-(6aS,11aS)-[³H]maackiain over (?)-(6aR, 11aR)-[¹⁴C]maackiain into (+)-(6aR, 11aR)-pisatin, establishing that the 6a-hydroxylation of pterocarpans proceeds with retention of configuration. (+)- (6aR,11aR)-6a-hydroxymaackiain was similarly incorporated much better than (?)-(6aS,11aS)-6a- hydroxymaackiain. Where (?)-isomers were incorporated, optical activity measurements on the pisatin produced indicated significant synthesis of (?)-pisatin as well as the normal (+)-pisatin. 7,2′-Dihydroxy-4′,5′- methylenedioxyisoflav-3-ene and both enantiomers of 7,2′-dihydroxy-4′,5′-methylenedioxyisoflavan were poor precursors of pisatin.     

The accumulation of five fluorescent compounds in the cotton leaf induced by cell-free extracts of Aspergillus flavus

(?)-Cryptocaryalactone (6-[2-acetoxy-4-phenyl-3-butenyl]-5,6-dihydro-2-pyranone) and (?)-deacetylcryptocaryalactone (6-[2-hydroxy-4-phenyl-3-butenyl]-5,6-dihydro-2-pyranone) isolated from Cryptocarya moschata seeds are natural germination inhibitors. Applied at 0.004 M, the second compound completely arrested germination of velvetleaf (Abutilon theophrasti) and decreased the germination rate of soybeans, but did not appear to affect corn. The first compound was not as effective; 0.004 M reduced velvetleaf germination 50%.     

Isolation of a New Cytokinin from Immature Yellow Lupin Seeds

A new cytokinin was isolated from methanol extracts of immature lupin seeds (Lupinus luteus) through successive purification of charcoal adsorptions, silver precipitations, ion exchange and paper chromatography. The structure was confirmed by spectral data and synthesis as (?)-6-N-(4-hydroxy-3-methylbutylamino)purine, (?)-dihydrozeatin (I).