Novel N-oxide derivatives of benzyltetrahydroisoquinoline alkaloid from the tubers of Stephania viridiflavens H.S. Lo et M. Yang

An investigation on the phytochemistry of the medicinal plant Stephania viridiflavens H.S. Lo et M. Yang led to isolate two new naturally occurring benzyltetrahydroisoquinoline alkaloids, (+)-1S, 2R-laudanidine-N_β-oxide 2 and (+)-1S, 2S-laudanidine-N_α-oxide 3, along with four known benzyltetrahydroisoquinoline alkaloids: (+)-laudanidine 1, (+)-reticuline 4, (+)-1S, 2R-reticuline-N_β-oxide 5 and (+)-1S, 2S-reticuline-N_α-oxide 6. The structure and the stereochemistry of these compounds were determined on the basis of spectroscopic methods and also confirmed by partial synthesis. To examine putative acetycholinesterase (AChE) inhibitory or cytotoxic activities, various bioassays were performed, the N-oxide derivatives (5 and 6) demonstrated more potent cytotoxicity than the corresponding free base.     

Chemical investigation of drug-like compounds from the Australian tree,Neolitsea dealbata

Two of the four parameters in the ‘rule of five’, molecular weight and log P, which can be detected and predicted by mass spectrometry and compound retention on reversed-phase HPLC, were used as guidelines in natural product isolation. A new aporphine alkaloid, (6aR)-normecambroline (1), was isolated from the bark of Neolitsea dealbata (R. Br.) Merr. Its structure was determined on the basis of NMR, MS and CD analysis. It is the first time the absolute configuration of the roemerine-N-oxide was assigned for both roemerine-N_α-oxide (3) and roemerine-N_β-oxide (4). Physico-chemical property evaluation demonstrated all alkaloids had no Lipinski violation. Compound 1 inhibited selectively against cervical cancer cells (HeLa) with an IC₅₀ of 4.0 μM.     

Concerning the biosynthesis of prostaglandin I2

Two diastereoisomers, 5R,6R-5-hydroxy-6(9α)-oxido-11α,15S-dihydroxyprost-13-enoic acid (7) and 5S,6S-5-hydroxy-6(9α)-oxido-11α,15S-dihydroxyprost-13-enoic acid (10) were synthesized for evaluation as possible biosynthetic intermediates in the enzymatic transformation of PGH₂ or PGG₂ into PGI₂. The synthetic sequence entails the stereospecific reduction of the 9-keto function in PGE₂ methyl ester after protecting the C-11 and C-15 hydroxyls as tbutyldimethylsilyl ethers. The resulting PGF_2α derivative was epoxidized exclusively at the C-5 (6) double bond to yield a mixture of epoxides, which underwent facile rearrangement with SiO₂ to yield the 5S,6S and 5R,6R-5-hydroxy-6(9α)-oxido cyclic ethers. It was found that dog aortic microsomes were unable to transform radioactive 9β-5S,6S[³H] or 9β-5R,6R[³H]-5-hydroxy-6(9α)-oxido cyclic ethers into PGI₂. Also, when either diastereoisomer was included in the incubation mixture, neither isomer diluted the conversion of [1-¹⁴C]arachidonic acid into [1-¹⁴C]PGI₂.     

Comparative study of the inhibition of sterol biosynthesis in Rubus fruticosus suspension cultures and zea mays seedlings by N-(1,5,9-trimethyldecyl)-4α,10-dimethyl-8-aza-trans-decal-3β-ol and derivatives

The nitrogen substituents present in tridemorph and fenpropimorph, which are systemic fungicides, have been linked to an 8-aza-bicyclic skeleton leading to N-(1,5,9-trimethyldecyl)-4α,10-dimethyl-8-aza-trans-decal-3β-ol and N-(3-(4-tert-butylphenyl-)2-methyl)-propyl-8-aza-4α,10-dimethyl-trans-decal-3β-ol respectively. The latter two compounds present in a stable molecule key structural elements of unstable C-8 and C-9 carbocationic high-energy intermediates which occur during the reactions catalysed by the Δ⁸ → Δ⁷-sterol isomerase and the cycloeucalenol-obtusifoliol isomerase, respectively. When given to either bramble cell suspension cultures or maize seedlings, they led to a spectacular accumulation of 9β,19-cyclopropyl sterols and were in that respect much more efficient than any known molecules and in particular than the N-benzyl decalin previously described which led to accumulation of Δ⁸-sterols. Surprisingly, treatment of the plant cells by the N-oxide derivatives of the N-benzyl decalin resulted in dramatic accumulation of Δ^8,14-sterols.     

Zur biogenese des aza-oxa-spiran-systems der steroidalkaloide vom spirosolan-typ in Solanaceen

5α,6-³H₂-Solacongestidine and 5α,6-³ H₂-(22S)-dihydrosolacongestidine administered to Solanum dulcamara as well as 16-³H₂-(22S: 25R)-22,26-epimino- cholest-5-en-3β-ol (25-isodihydroverazine) and 7α-³H-(22S: 25R)-22,26-epimino-cholest-5-en-3β,16β-diol administered to Solanum laciniatum were converted to coladulcidine and solasodine, respectively. These results are discussed in relation to spirosolane alkaloid biosynthesis.     

Stereochemistry of tropane alkaloid formation in Datura

Five-month-old Datura innoxia plants were fed via the roots with either d(+)-hygrine-[2′-¹⁴C] or l(?)-hygrine-[2′-¹⁴C]. After 7 days the root alkaloids 3α,6β-ditigloyloxytropane, 3α,6β-ditigloyloxytropan-7β-ol, hyoscine, hyoscyamine and cuscohygrine were isolated from both groups of plants. d(+) but not l(?)-hygrine acts as a precursor for the tropane alkaloids whereas both enantiomers appeared to serve equally well in the biosynthesis of cuscohygrine.     

Biosynthesis of the tigloyl esters in Datura: The role of 2-methylbutyric acid

Datura innoxia plants were wick fed with (±)-2-methylbutyric acid-[1-¹⁴C] and harvested after 7 days. The root alkaloids 3α,6β-ditigloyloxytropane and 3α,6β-ditigloyloxytropan-7β-ol were isolated and degraded. In each case the radioactivity was located in the ester carbonyl group indicating that this acid is an intermediate in the biosynthesis of tiglic acid from l-isoleucine. On the other hand, (±)-2-hydroxy-2-methylbutyric acid-[1-¹⁴C], which was fed to hydroponic cultures of Datura innoxia alongside isoleucine[U-¹⁴C] positive control plants, is not an intermediate.     

Alkaloids from the leaves of Strychnos wallichiana

The leaves of Strychnos wallichiana Steud. ex. DC. from Bangladesh contain icajine and novacine as their major alkaloids. Smaller amounts of strychnine, brucine, pseudostrychnine, pseudobrucine, N-methyl-sec.-pseudo-β-colubrine, 14-hydroxyicajine, strychnine N-oxide, and brucine N-oxide are also present. The new bases 14 hydroxynovacine and icajine N-oxide have been isolated.     

Alkaloids from trunk bark of Hernandia nymphaeifolia

Six new alkaloids, (+)-ovigerdimerine, 4-methoxyoxohernandaline, 7-formyldehydrohernangerine, 5,6-dimethoxy-N-methylphthalimide, 7-hydroxy-6-methoxy-1-methylisoquinoline and (+)-vateamine-2′-β-N-oxide, along with one new dialdehyde, hernandial, have been isolated and characterized from the trunk bark of Hernandia nymphaeifolia. The structures of these compounds were elucidated by spectral analyses.     

Biosynthesis of the tigloyl esters of Datura: Cis-trans isomerism

Datura innoxia plants were wick fed with angelic acid-[1-¹⁴C] and l-isoleucine-[U-¹⁴C] to act as a positive control. After 7 days the root alkaloids 3α-tigloyloxytropane, 3α,6β-ditigloyloxytropane, and 3α,6β-ditigloyloxytropan-7β-ol were isolated and it was determined that angelic acid is not a precursor for the tigloyl moiety of these alkaloids. Tiglic acid-[1-¹⁴C] which was fed via the roots to hydroponic cultures of Datura innoxia, was incorporated to a considerable degree after 8 days.     

Biosynthesis of sitosterol in barley seedlings

A method is described for the chemical synthesis of stigmasta-5,24-dien-3β-ol-[26-¹⁴C] and (24S)-24-ethylcholesta-5,25-dien-3β-ol-[26-¹⁴C] (clerosterol). 28-Isofucosterol-[7-³H₂] fed to developing barley seedlings (Hordeum vulgare) was incorporated into sitosterol and stigmasterol confirming the utilisation of a 24-ethylidene sterol intermediate in 24α-ethyl sterol production in this plant. Also, the use of mevalonic acid-[2-¹⁴C(4R)-4-³H₁] verified the loss of the C-25 hydrogen of 28-isofucosterol during its conversion into sitosterol and stigmasterol in agreement with the previously postulated isomerisation of the 24-ethylidene sterol to a Δ²⁴⁽²⁵⁾-sterol prior to reduction. However, feeding stigmasta-5,24-dien-3β-ol [26-¹⁴C] to barley seedlings gave very low incorporation into sitosterol. Attempts to trap radioactivity from mevalonic-[2-¹⁴C(4R)-4-³H₁] in stigmasta-5,24-dien-3β-ol when this unlabelled sterol was administered to barley seedlings gave only a very small incorporation although both 28-isofucosterol and sitosterol were labelled.     

Sterols with unusual nuclear unsaturation from three cultured marine dinoflagellates

Several new 4α-methyl sterols with unusual unsaturation in the Δ⁸⁽¹⁴⁾-or Δ¹⁴-positions, 4α,24S-dimethyl-5α-cholest-8 (14)-en-3β-ol, 4α-methyl-24ξ-ethyl-5α-cholest-8(14)-en-3β-ol, 4α-methyl-24(Z)-ethylidene-5α-cholest-8(14)- en-3β-ol, 4α,23 (or 22),24ξ-trimethyl-5α-cholesta-8(14),22-dien-3β-ol, 4α,24S(or 23ξ)-dimethyl-5α-cholest-14-en-3β-ol and 14-dehydrodinosterol, have been isolated from extracts of the cultured marine dinoflagellates Amphidinium carterae, A. corpulentum and Glenodinium sp. 4α-Methyl-24ξ-ethyl-5α-cholestan-3β-ol was isolated from the steryl ester fraction of Glenodinium sp. The structures of these new sterols are based upon extensive 360 MHz ¹H NMR and MS analyses.     

Biosynthesis of Δ5.23 sterols in etiolated coleoptiles from Zea mays

In addition to the previously found ergosta-5, E-23-dien-3β-ol and 5α-ergosta-7, E-23-dien-3β-ol, the following Δ23 sterols have been identified in etiolated maize coleoptiles: cyclosadol, 4α, 14α-dimethyl-5α-ergosta-8, E-23-dien-3β-ol, 4α, 14α-dimethyl-9β, 19-cyclo-5α-ergosta-8, E-23-dien-3β-ol and 4α-methyl-5α-ergosta-7, E-23-dien-3β-ol. The incubation of maize coleoptile microsomes in the presence of cycloartenol and of [¹⁴C-methyl]S-adenosyl methionine gave a mixture of labelled 24-methylene cycloartanol and cyclosadol. No trace of cyclolaudenol could be detected in these conditions. It is suggested that Δ²³ sterols are products of the C-24 methyltransferase reaction and they probably do not arise from a Δ²⁴ → Δ²³ isomerization occurring at a later stage of the biosynthesis. The Δ¹³-sterols may play an intermediary role in the biosynthesis of 24-methyl sterols in this plant material.     

Skin irritant diterpene orthoesters of the daphnane type from Peddiea africana and P. Volkensii

From roots of Peddiea volkensii (Thymelaeaceae) the irritant factors V₁ and V₂ and from roots of P. africana the irritant factor A₁ were isolated. Their structures are the 9,13,14-ortho-(2,4,6-decatrienoates) of 5β-hydroxyresiniferonol-6α,7α-oxide (V₁) and of 5β,12β-dihydroxyresiniferonol-6α,7α-oxide (A₁) and the 12-O-acetate of the latter (V₂). Factors V₁ and V₂ do not exhibit tumour-promoting activity in the standard initiation-promotion protocol on mouse skin, although V₁ is a moderate irritant.     

Alkaloids from Galanthus rizehensis

Two new Amaryllidaceae alkaloid N-oxides, incartine N-oxide (1) and lycorine N-oxide (2) together with one β-carboline alkaloid, 1-acetyl-β-carboline (3) and six known alkaloids namely, incartine (4), N-trans feruloyltyramine (5), lycorine (6), O-methylnorbelladine (7), vittatine (8) and 11-hydroxyvittatine (9) were isolated from Galanthus rizehensis Stern (Amaryllidaceae). The structures of the alkaloids were elucidated by spectroscopic analyses (UV, IR, MS, 1D and 2D NMR). Acetylcholinesterase inhibitory activity potentials of the compounds were also determined.     

Steroids from the leaves of Chinese Melia azedarach and their cytotoxic effects on human cancer cell lines

Three new (1-3) and several known (4-6) steroids were isolated from the leaves of Chinese Melia azedarach. The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR techniques and mass spectrometry to be (20S)-5,24(28)-ergostadiene-3β,7α,16β,20-tetrol (1), (20S)-5-ergostene-3β,7α,16β,20-tetrol (2), and 2α,3β-dihydro-5-pregnen-16-one (3). The cytotoxicities of the isolated compounds against three human cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and (20S)-5-stigmastene-3β,7α,20-triol (4) were found to show significant cyctotoxic effects with IC₅₀s from 12.0 to 30.1 μg/mL.     

New immunomodulatory steroidal alkaloids from Sarcococa saligna

Two new steroidal alkaloids, (20 S)-(bennzamido)-3β-(N,N-dimethyamino)-pregnane (1), and (20 S)-(bennzamido)-pregnane-3-one- (2), and two known steroidal alkaloids, pachysanaximine A (3) and 3β, 20α-diacetamido-5α-pregnane (4) were isolated from the whole plant of Sarcococca saligna. The structures of these compounds were identified with the help of spectroscopic techniques while spectra for known compounds were compared with spectra reported in literature. The immunomodulatory potential of the new compounds were found to be significant and dose dependent. Compound 1 showed inhibition of T cells proliferation at 10 μg/mL (95%), and inhibition of IL-2 production with an IC50 = 1.6 μg/mL.     

Polyhydroxylated steroid compounds from the Far Eastern starfish <Emphasis Type="Italic">Distolasterias nipon</Emphasis>

Two new steroid glycosides: distolasteroside D₆, (24S)-24-O-(β-D-xylopyranosyl)-5α-cholestane-3β,6α,8,15β,16β,24-hexaol, and distolasteroside D₇, (22E,24R)-24-O-(β-D-xylopyranosyl)-5α-cholest-22-ene-3β,6α,8,15β,24-pentaol were isolated along with the previously known distolasterosides D₁, D₂, and D₃, echinasteroside C, and (25S)-5α-cholestane-3β4β,6α,7α,8,15α,16β,26-octaol from the Far Eastern starfish Distolasterias nipon. The structures of new compounds were elucidated by NMR spectroscopy and MALDI TOF mass spectrometry. Like neurotrophins, distolasterosides D₁, D₂, and D₃ were shown to induce neuroblast differentiation in a mouse neuroblastoma C1300 cell culture.     

Growth stimulation ofEuphorbia lathyris L. by GA4+7 and BA

Container-grownEuphorbia lathyris plants were treated with foliar sprays of various combinations of BA and GA₄₊₇ or 0–3600 mg L^?1 Promalin (1∶1 BA + GA₄₊₇) in separate experiments. GA₄₊₇ and Promalin stimulated plants to grow taller. BA and Promalin promoted axillary shoot growth. Multiple applications of Promalin stimulated branching more than single treatments. Dry weight accumulation was stimulated only if the growth regulators were applied to 28–33-cm and not to 56-cm tall plants. Chemical names used: (1α, 2β, 4aα, 4bβ, 10β)-2,4a,7-trihydroxy-1-methyl-8-methylenegibb-3-ene-1,10-dicarboxylic acid 1,4a-lactone (GA₄₊₇),N-(phenylmethyl)-H-purin-6-amine (BA), and Promalin [1∶1 (wt/wt) GA₄₊₇ and BA].     

Indole alkaloids from Hannoa klaineana roots

1-Methoxycanthin-6-one, rhyncophylline, isorhyncophylline and four new alkaloids, ethyl-β-carboline-1-propionate, ethyl-β-carboline-2N-oxide-1-propionate, 1-ethyl-β-carboline and 1-ethyl-β-carboline-2N-oxide, were isolated from three different samples of Hannoa klaineana roots.