(+)-2,3-Trans-pubeschin,the first catechin analogue of peltogynoids from Peltogyne pubescens and P. venosa

The heartwoods of Peltogyne pubescens and P. venosa contain the predominant pair (+)-peltogynol and (+)-mopanol, their 4-epimers, (+)-peltogynol B and (+)-mopanol B, together with the first catechin analogue of peltogynol, (+)-2,3- trans-pubeschin. These are accompanied by ±-2,3-cis- and ±-2,3-trans-3-O-methylfustins, and by α, 2′,3,4,4′-pentahydroxychalcone. Other minor metabolises are 4′,7-dihydroxy- and 3′,4′,7-trihydroxy-flavanones and 5,6-dihydroxyphthalide. (+)-2,3-Trans-pubeschin trimethyl ether was synthesized by reduction of the corresponding (+)-2,3-trans-peltogynone analogue with NaBH₄/BF₃ in diglyme, and its absolute configuration shown to be 2R: 3S.     

Fumariaceae alkaloids including the biogenetic precursor of cularine

Corydalis claviculata has yielded (+)-crassifoline, the first 7,8,3′,4′-oxygenated benzylisoquinoline and biogenetic precursor of cularine, as well as the new cularine alkaloids (+)-sarcocapnidine, (+)-claviculine and (+)-O-methylcularicine.     

Variabilin,a 6a-hydroxypterocarpan from Dalbergia variabilis

Bark and wood of the creeper Dalbergia variabilis contain the previously described friedelin, O-acetyl-oleanolic acid, formononetin, 8-O-methylretusin, (+)-vestitol, (±)-mucronulatol, (+)- and (±)-medicarpin, besides (+)-variabilin [(6aR,11aR)-6a-hydroxy-3,9-dimethoxypterocarpan]. This structure was confirmed by the conversion of (+)-variabilin into di-O-methylcoumestrol.     

Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris

The sesquiterpenoid (+)-nootkatone is a highly demanded and highly valued aroma compound naturally found in grapefruit, pummelo or Nootka cypress tree. Extraction of (+)-nootkatone from plant material or its production by chemical synthesis suffers from low yields and the use of environmentally harmful methods, respectively. Lately, major attention has been paid to biotechnological approaches, using cell extracts or whole-cell systems for the production of (+)-nootkatone. In our study, the yeast Pichia pastoris initially was applied as whole-cell biocatalyst for the production of (+)-nootkatone from (+)-valencene, the abundant aroma compound of oranges. Therefore, we generated a strain co-expressing the premnaspirodiene oxygenase of Hyoscyamus muticus (HPO) and the Arabidopsis thaliana cytochrome P450 reductase (CPR) that hydroxylated extracellularly added (+)-valencene. Intracellular production of (+)-valencene by co-expression of valencene synthase from Callitropsis nootkatensis resolved the phase-transfer issues of (+)-valencene. Bi-phasic cultivations of P. pastoris resulted in the production of trans-nootkatol, which was oxidized to (+)-nootkatone by an intrinsic P. pastoris activity. Additional overexpression of a P. pastoris alcohol dehydrogenase and truncated hydroxy-methylglutaryl-CoA reductase (tHmg1p) significantly enhanced the (+)-nootkatone yield to 208 mg L⁻¹ cell culture in bioreactor cultivations. Thus, metabolically engineered yeast P. pastoris represents a valuable, whole-cell system for high-level production of (+)-nootkatone from simple carbon sources.     

(+)-Pinpollitol: A di-O-methyl d-(+)-chiro-inositol from Pinus radiata

(+)-Pinpollitol, a new cyclitol recently isolated from the pollen of Pinus radiata, was found in the needles of this species. (+)-Pinpollitol was found to be a di-O-methyl ether Of d-(+)-chiro-inositol, and tentative isomeric structures have been proposed for the cyclitol. (+)-Pinpollitol is the first di-O-methyl inositol to be found in a gymnosperm and is one of only three di-O-methyl inositols yet found in nature.     

(+)-5,17-dehydromatrine N-oxide,a new alkaloid in Euchresta japonica

A new lupin alkaloid, (+)-5,17-dehydromatrine N-oxide, was isolated from the fresh aerial parts of Euchresta japonica. Its structure was confirmed by spectrometric data and by direct comparison with a synthetic sample, prepared from (+)-sophoranol ((+)-5-hydroxymatrine). It was also concluded that (+)-5,17-dehydromatrine N-oxide and (+)-matrine N-oxide possess the same configuration with respect to the asymmetric nitrogen by NMR spectra.     

Biosynthesis of (+)-catechin glycosides using recombinant amylosucrase from Deinococcus geothermalis DSM 11300

Amylosucrase (ASase, EC 2.4.1.4) is a glucosyltransferase that hydrolyzes sucrose into glucose and fructose and produces amylose-like glucan polymers from the released glucose. (+)-Catechin is a plant polyphenolic metabolite having skin-whitening and antioxidant activities. In this study, the ASase gene from Deinococcus geothermalis (dgas) was expressed in Escherichia coli, while the recombinant DGAS enzyme was purified using a glutathione S-transferase fusion system. The (+)-catechin glycoside derivatives were synthesized from (+)-catechin using DGAS transglycosylation activity. We confirmed the presence of two major transglycosylation products using TLC. The (+)-catechin transglycosylation products were isolated using silica gel open column chromatography and recycling-HPLC. Two (+)-catechin major transfer products were determined through ¹H and ¹³C NMR to be (+)-catechin-3′-O-α-d-glucopyranoside with a glucose molecule linked to (+)-catechin and (+)-catechin-3′-O-α-D-maltoside with a maltose linked to (+)-catechin. The presence of (+)-catechin maltooligosaccharides in the DGAS reaction was also confirmed via recycling-HPLC and enzymatic analysis. The effects of various reaction conditions (temperature, enzyme concentration, and molar ratio of acceptor and donor) on the yield and type of (+)-catechin glycosides were investigated.     

Alkaloids of Thermopsis Lupinoides

Ammodendrine, together with seven other known lupin alkaloids, was isolated from Thermopsis lupinoides. (+)-Lupanine (+)-17-oxolupanine occurred together with (?)anagyrine, (?)-baptifoline, (?)-cytisine, (?)-N-methylcytisine (?)N-formylcytisine. These alkaloids have the opposite stereochemistry to that of (+)-lupanine and (+)-17-oxolupanine. The distribution of alkaloids in fresh flowers, leaves, stems roots of this plant was also examined.     

(−)-Epilamprolobine and its N-oxide,lupin alkaloids from Sophora tomentosa

From the fresh leaves of Sophora tomentosa, three new lupin alkaloids, (?)-epilamprolobine, (+)-epilamprolobine N-oxide and 5-(3′-methoxycarbonylbutyroyl)aminomethyl-trans-quinolizidine N-oxide, have further been isolated along with (+)-matrine, (+)-matrine N-oxide, (+)-sophocarpine N-oxide, (?)-anagyrine, (?)- baptifoline, (?)-cytisine, (?)-N-methylcytisine, (?)-N-formylcytisine, (?)-N-acetylcytisine and (±)-ammodendrine. The absolute configurations of (+)-epilamprolobine N-oxide (1R:5R:6S) and (?)-epilamprolobine (5R:6S) have also been established by spectroscopic data and by comparison with synthetic (+)-epilamprolobine (5S:6R)derived from (?)-lupinine (5R:6R). (?)-Epilamprolobine is a diastereomer of (+)-lamprolobine (5R:6R) in Lamprolobium fruticosum and 5-(3′-methoxycarbonylbutyroyl) aminomethyl-trans-quinolizidine N-oxide is presumed to be an artefact. A biosynthetic pathway for the formation of (?)-epilamprolobine is also proposed.     

Vestitol and vesticarpan,isoflavonoids from Machaerium vestitum

The wood of Machaerium vestitum contains the previously described O-acetyloleanolic aldehyde, formononetin, (+)-medicarpin, and (?)-mucronulatol, besides (+)-vestitol [(3S)-7,2′-dihydroxy-4-methoxyisoflavan] and (+)-vesticarpan [(6aS,11aS)-3,10-dihydroxy-9-methoxypterocarpan]. The constitutions of vestitol and vesticarpan were deduced by spectra and confirmed by syntheses.     

New coumarins from Coleonema album

Six coumarins have been isolated from the aerial parts of Coleonema album and identified as ulopterol, 7-(3′, 3′-dimethylallyloxy)-coumarin, (R)-(+)-2′,3′-epoxy-suberosin, and the novel coumarins (R)-(+)-7-(2′, 3′-epoxy-3′-methylbutoxy)-coumarin, (R)-(+)-7-(2′,3′-dihydroxy-3′-dihydroxy-3′-methylbutoxy)-coumarin and (R)-(+)-7-methoxy-8-(2′,3′-epoxy-3′-methylbutoxy)-coumarin.     

(+)-[C-11]-cis-N-benzyl-normetazocine: A selective ligand for sigma receptors in vivo

The in vivo biodistribution profile of the novel sigma (σ) receptor ligand (+)-[C-11]-cis-N-benzyl-normetazocine ([C-11]-(+)-NBnNM) in mouse brain was examined. This radioligand displayed high brain uptake and a distribution consistent with the density of σ receptors. Brain radioactivity levels peaked at 15 min postinjection and were largely maintained (ca. 80% of maximal values) up to 90 min postinjection. Pretreatment with several different σ ligands (haloperidol, (+)-pentazocine, DuP 734, ifenprodil) effectively inhibited [C-11]-(+)-NBnNM binding in a dose-dependent manner in all brain regions. [C-11]-(+)-NBnNM binding sites were shown to be saturable with unlabeled (+)-NBnNM (ED50 = 0.02 mg/kg) and enantioselectively inhibited by the optical isomers of pentazocine. A blocking dose of the dopamine D2 antagonist spiperone (1 mg/kg) did not significantly inhibit [C-11]-(+)-NBnNM binding. Pretreatment with the phencyclidine (PCP) blocker 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP) did not significantly alter total brain tissue radioactivity. Thus, [C-11]-(+)-NBnNM binds with high specificity and selectivity to σ receptors in vivo and offers excellent potential to study σ receptors in living human brain via positron emission tomography.     

(+)-Isorangiformic acid,a lichen substance from Lecanora stenotropa

(+)-Isorangiformic acid from the lichen Lecanora stenotropa has been shown to be (+)-2S-methoxycarbonyl-3S-heptadecanedicarboxylic acid.     

Preparation of (+)-Trans-Isoalliin and Its Isomers by Chemical Synthesis and RP-HPLC Resolution

Naturally occurring (+)-trans-isoalliin, (R_CR_S)-(+)-trans-S-1-propenyl-L-cysteine sulfoxide, is a major cysteine sulfoxide in onion. The importance of producing it synthetically to support further research is very well recognized. The (+)-trans-isoalliin is prepared by chemical synthesis and reversed-phase (RP)-HPLC. First, S-2-propenyl-L-cysteine (deoxyalliin) is formed from L-cysteine and allyl bromide, which is then isomerized to S-1-propenyl-L-cysteine (deoxyisoalliin) by a base-catalyzed reaction. A mixture of cis and trans forms of deoxyisoalliin is formed and separated by RP-HPLC. Oxidation of the trans form of deoxyisoalliin by H₂O₂ produces a mixture of (−)- and (+)-trans-isoalliin. Finally, RP-HPLC is used successfully in separating (−)- and (+)-trans-isoalliin, and hence, (+)-trans-isoalliin is synthesized for the first time in this study. In addition, the (±) diastereomers of cis-isoalliin are also separated and purified by RP-HPLC.     

Flavonoids and tannins of Acacia species

The heartwoods of Acacia giraffae and A. galpinii were selected from South African Acacias as representative of those with abnormally high and minimal tannin contents respectively. A. galpinii contains amongst other analogues, the first natural (+)-2,3-trans-3,4-trans-teracacidin (7,8,4′-trihydroxy-flavan-3,4-diol and novel 3-O-methyl-, 7,8-di-O-methyl- and 7,8,4′-tri-O-methylflavonol analogues. (−)-2,3-cis-3,4-cis-Melacacidin (7,8,3′,4′-tetrahydroxyflavan-3,4-diol) is also present, but tannins are absent. By contrast, from the large excess of leueofisetinidin tannins which characterizes the wood of A. giraffae, only (+)-catechin, (+)-2,3-trans-3,4-trans-leucofisetinidin (7,3′,4′,trihydroxyflavan-3,4-diol and all-trans-(+)-leueofisetinidin-(+)-catechin could be isolated.     

New lignans from leaves of Macropiper excelsum

Four new lignans, (+)-diayangambin; (+)-excelsin; (+)-epiexcelsin and (+)-demethoxyexcelsin, were isolated from leaves of Macropiper excelsum and their structures and configurations have been determined by spectroscopic studies. Diayangambin is only the second naturally occurring diaxially substituted 3,7-dioxabicyclo-[3,3,0]-octane to have been isolated.     

Geovanine,a new azaanthracene alkaloid from Annona ambotay aubl.

The new azaanthracene geovanine was isolated from the trunkwood of Annona ambotay Aubl. together with liriodenine, O-methylmoschatoline and other known substances, the flavonoids kaempferol, quercetin, (+)-dihydrokaempferol, (+)-dihydroquercetin, (±)-eriodictiol and (+)-catechin and the steroids sitosterol and 5α-stigmastan-3,6-dione.     

Catechins with (+)-epi-configuration in nature

(+)-Epicatechin has been isolated from various species of Palmae and (+)-epiafzelechin from Livinstona chinensis. This is the first time that catechins with (+)-epi-configuration have been found in natural sources.     

Furocoumarins from Angelica pachycarpa

A novel furocoumarin isolated from unripe fruits of Angelica pachycarpa has been characterized as (+)-tert- O-methylbyakangelicin. (+)-tert-O-Methyloxypeucedanin hydrate, neobyakangelicol, (±)-byakangelicol, (+)-byakangelicin, phellopterin, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, pangeline and umbelliprenin were also identified along with (±)-byakangelicin monoacetate, which proved to be an artifact.     

Phenolic glucosides from Olea europaea subs. africana

Two new lignan glucosides, (+)-1-acetoxypinoresinol 4″-methyl ether 4′-β-d-glucoside and (+)-1-hydroxypinoresinol 4′-β-d-glucoside, together with three known glucosides, (+)-1-acetoxypinoresinol 4′-β-d-glucoside, esculin and oleuropein, were isolated from the bark of Olea europaea subs africana.