Biosynthesis of the Indole Alkaloids. Cell-free Systems from Catharanthus roseus Plants

Cell-free systems from Catharanthus roseus plants are utilized for various studies relating to the biosynthesis of indole alkaloids. Tryptamine ( 5 ) and secologanin ( 6 ), two fundamental building units, are shown to be incorporated into the alkaloid vindoline ( 7 ). In another study, catharanthine ( 18 ) and vindoline ( 7 ) are utilized by this enzyme system and coupled to the important bisindole biointermediate 3′,4′-anhydrovinblastine

1 The previously [20] used name for 17 , 3′, 4′-dehydrovinblastine, is incorrect.

( 17 ). The latter substance is, in turn, incorporated and converted to the natural alkaloids leurosine ( 8 ), Catharine ( 9 ) and vinblastine ( 10 ), thereby providing information about the biosynthesis of these complex molecules. High pressure liquid chromatography assay of the enzymic mixture sheds light on the enzymes involved in the coupling of 18 and 7 .     

Alkaloids from the Twigs of Catharanthus roseus

Chemistry of Natural Compounds -     

Monoterpene Indole Alkaloids with Cav3.1 T-Type Calcium Channel Inhibitory Activity from Catharanthus roseus

Catharanthus roseus is a well-known traditional herbal medicine for the treatment of cancer, hypertension, scald, and sore in China. Phytochemical investigation on the twigs and leaves of this species led to the isolation of two new monoterpene indole alkaloids, catharanosines A (1) and B (2), and six known analogues (3–8). Structures of 1 and 2 were established by ¹H-, ¹³C- and 2D-NMR, and HREIMS data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 2 represented an unprecedented aspidosperma-type alkaloid with a 2-piperidinyl moiety at C-10. Compounds 6–8 exhibited remarkable Ca_v3.1 low voltage-gated calcium channel (LVGCC) inhibitory activity with IC₅₀ values of 11.83 ± 1.02, 14.3 ± 1.20, and 14.54 ± 0.99 μM, respectively.     

Indole Alkaloids from the Roots of Ervatamia hainanensis

Evratamia hainanensis Tsiang, is distributed in the mountain and forest regions of 100-500 metres height in the southern part of China. Its root has been used for the treatment of stomachache, dysentery, rheumatic arthritis, hypertension and virus hepatit…     

New Sesquiterpene Glycosides from Culture Hairy Roots of Catharanthus roseus

Two new compounds cadin-2-en-1β-ol-1β-D-glucuronopyranoside （1）, guaia-l,7-dien-3β,13-diol-13α-D- glucofuranoside （2） along with three known compounds have been isolated from the culture hairy roots of Catharanthus roseus. Their structures have been elucidated with the help of 500 MHz NMR using 1D and 2D spectral methods： viz： ^1H and ^13C NMR, ^1H-^1H COSY, ^1H-^13C HETCOR and DEPT aided by ELMS, FAB-MS, HR-FABMS and IR spectroscopy.     

Flavonoid Aglycones and Indole Alkaloids from the Roots of Acacia Confusa

From the methanolic extract of the roots of Acacia confusa Merr. (Leguminosae), (‐)‐2,3‐cis‐3,4‐cis‐4′‐methoxy‐3,3′,4,7,8‐pentahydroxyflavan ( 1 ), (‐)‐2,3‐cis‐3,4‐cis‐3,3′,4,4′,7,8‐hexahydroxyflavan ( 2 ), (‐)‐2,3‐trans‐3′,4′,7,8‐tetrahydroxydihydroflavonol ( 3 ), (+)‐catechin ( 4 ), (‐)‐epicatechin ( 5 ), 3′,4′,7,8‐tetrahydroxyflavonol ( 6 ) together with N‐methyltryptamine ( 7 ) and N,N‐dimethyltryptamine ( 8 ) were isolated, and their structures were established by analysis of their spectroscopic data. Among them, compound 1 was a new flavonoid. Additionally, the results of chromatographic bioassay on lettuce seeds indicated that compounds 7 and 8 exhibited significant phytotoxicity at a concentration lower than 14 mM.     

Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects

Maerua siamensis (Capparaceae) roots are used for treating pain and inflammation in traditional Thai medicine. Eight new indole alkaloids, named maeruanitriles A and B, maeroximes A–C, and maeruabisindoles A–C, were isolated from them. Spectroscopic methods and computational analysis were applied to determine the structure of the isolated compounds. Maeroximes A–C possesses an unusual O-methyloxime moiety. The bisindole alkaloid maeruabisindoles A and B possess a rare azete ring, whereas maeruabisindole C is the first indolo[3,2-b]carbazole derivative found in this plant family. Five compounds [maeruanitriles A and B, maeroxime C, maeruabisindoles B, and C] displayed anti-inflammatory activity by inhibiting nitric oxide (NO) production in the lipopolysaccharide-induced RAW 264.7 cells. Maeruabisindole B was the most active inhibitor of NO production, with an IC₅₀ of 31.1 ± 1.8 μM compared to indomethacin (IC₅₀ = 150.0 ± 16.0 μM) as the positive control.     

Indole Alkaloids from Alocasia macrorrhiza

Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.     

Monoterpenoid Indole Alkaloids from Alstonia mairei

Three new monoterpenoid indole alkaloids, (14α,15α)‐14,15‐epoxyaspidofractinine ( 1 ) and maireines A and B ( 2 and 3 , resp.), together with 19 known alkaloids, were isolated from the leaves and twigs of Alstonia mairei. The structures of the new compounds were elucidated by 1D‐ and 2D‐NMR spectroscopic methods in combination with MS experiments.     

New Indole Alkaloids from Rauvolfia yunnanensis

Three new indole alkaloids, 10‐methoxy‐16‐de(methoxycarbonyl)pagicerine ( 1 ), (5β)‐17‐O‐deacetyl‐5,11‐dimethoxyakuammiline ( 2 ), and ((16S,19E)‐N¹‐(hydroxymethyl)isositsirikine ( 3 ) were isolated from the roots of Rauvolfia yunnanensis, together with seven known alkaloids. The structures of the new compounds were elucidated by in‐depth spectroscopic and mass‐spectrometric analyses.     

Indole Alkaloids from the Leaves of Anthocephalus chinensis

Anthocephalusine A ( 1 ) and 3β‐isodihydrocadambine 4‐oxide ( 2 ) were isolated from the leaves of Anthocephalus chinensis (Rubiaceae), together with five known compounds. The structures were established by spectroscopic methods including 2D‐NMR analyses.     

云南萝芙木叶吲哚生物碱

从栽培云南萝芙木(Rauvolfia yunnanensis Tsiang)叶的95%乙醇提取物中分离得到11个吲哚类生物碱: Caberine(1), 19-Ethoxyl-1-demethyl-Δ¹-17-acetylajmaline(2), Vellosimine(3), β-Yohimbine(4), Yohimbine(5), Vinorine(6), Picrinine(7), Nareline(8), Akuammicine(9), Strictamine(10), Reserpine(11). 采用UV, IR, MS和1D, 2D NMR方法对它们的结构进行了鉴定, 其中化合物2为新的吲哚生物碱, 化合物1, 8和9为首次从该属植物中分离得到.     

Indole Alkaloids from the Whole Plants of Ervatamia officinalis

Three new ervatamine‐type indole alkaloids, 6‐oxo‐16,20‐episilicine ( 1 ), 16,20‐episilicine ( 2 ), and 6,16‐didehydro‐20‐episilicine ( 6 ), along with seven known alkaloids, were isolated from the whole plants of Ervatamia officinalis. Their structures were elucidated by spectroscopic methods.     

Two New Indole Alkaloids from Evodia rutaecarpa

The tyuit of Evodia rutaecarpa (Juss.) Benth is a Chinese traditional drug (Wu-Chu-Yu).The components of Wu-Chu-Yu have been studied by several groups, including indolealkaloids,quinolone alkaloids. limonoids and other kinds]. Further chemical investigationofthis drug led us to isolate two new indole alkaloids 1 and 2. This is the first time toisolate indolinone alkaloids from this plant.Wuchuyuamide I (l ), was isolated as colorless needles, m,p. 261 -262<> C (CHCI,MeOH), [Q].=# 0(c 0…     

Two New Indole Alkaloids from Emmenopterys henryi

Two new indole alkaloids, 5‐oxodolichantoside ( 1 ) and deglycocadambine ( 2 ), were isolated from the twigs and leaves of Emmenopterys henryi, together with four known indole alkaloids and five known iridoids. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D‐ and 2D‐NMR experiments, and confirmed by single‐crystal X‐ray diffraction studies. This is the first report on the isolation of indole alkaloids from this species. The indole alkaloids were evaluated for their cytotoxic activities against five human cancer lines.     

云南蕊木茎中的抗炎吲哚生物碱

应用多种色谱和波谱学方法,从云南蕊木(Kopsia officinalis)茎中分离鉴定了27个单萜吲哚生物碱,包括7个新化合物kopsiofficines A～G和20个已知化合物.此外,建立脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症模型,通过测定IL-1β, PGE2和TNF-α炎症因子释放评价生物碱的抗炎活性.结果表明, kopsiofficines A (1), kopsiofficines B (2),kopsiofficines D(4),kopsiofficines F(6),kopsiofficines G(7), 12-methoxykopsine(11),kopsinoline(15),(-)-N-methoxy-carbonyl-11,12-methylenedioxykopsinaline(16),kopsinine(18)和kopsinic acid(20)表现出显著的抗炎活性,与阳性对照(地塞米松)基本相当.研究发现C-5位丙酮基取代的单萜吲哚生物碱的抗炎活性明显强于原型生物碱,推测丙酮基可能是抗炎活性的药效促进基团,研究结果为进一步的结构修饰...     

In Vitro Antidiabetic and Antioxidant Effects of Different Extracts of Catharanthus roseus and Its Indole Alkaloid,Vindoline

The Catharanthus roseus plant has been used traditionally to treat diabetes mellitus. Scientific evidence supporting the antidiabetic effects of this plant’s active ingredient-vindoline has not been fully evaluated. In this study, extracts of C. roseus and vindoline were tested for antioxidant activities, alpha amylase and alpha glucosidase inhibitory activities and insulin secretory effects in pancreatic RIN-5F cell line cultured in the absence of glucose, at low and high glucose concentrations. The methanolic extract of the plant showed the highest antioxidant activities in addition to the high total polyphenolic content (p < 0.05). The HPLC results exhibited increased concentration of vindoline in the dichloromethane and the ethylacetate extracts. Vindoline showed noticeable antioxidant activity when compared to ascorbic acid at p < 0.05 and significantly improved the in vitro insulin secretion. The intracellular reactive oxygen species formation in glucotoxicity-induced cells was significantly reduced following treatment with vindoline, methanolic and the dichloromethane extracts when compared to the high glucose untreated control (p < 0.05). Plant extracts and vindoline showed weaker inhibitory effects on the activities of carbohydrate metabolizing enzymes when compared to acarbose, which inhibited the activities of the enzymes by 80%. The plant extracts also exhibited weak alpha amylase and alpha glucosidase inhibitory effects.     

Alkaloids from the Roots of Stemona tuberosa

Four new alkaloids, didehydrotuberostemonine A ( 1 ), stemoninone ( 2 ), tuberostemospiroline ( 3 ), and tuberostemonine L ( 4 ), together with seven known alkaloids, were isolated from the roots of Stemona tuberosa. Their structures were elucidated on the basis of spectroscopic analysis. The known alkaloids were identified as 2‐oxostenine ( 5 ), tuberostemonine ( 6 ), sessilifoliamide H ( 7 ), tuberostemonone ( 8 ), didehydrotuberostemonine ( 9 ), bisdehydrostemoninine ( 10 ), and tuberostemoamide ( 11 ).     

Alkaloids from the Roots of Stemona cochinchinensis

Phytochemical investigation of the roots of Stemona cochinchinensis led to the isolation and structure elucidation of a new pyrido[1,2‐a]azepine‐type alkaloid, stemocochinamine ( 1 ), and of four new pyrrolo[1,2‐a]azepine‐type alkaloids, bisdehydrostemocochinine ( 2 ), isobisdehydrostemocochinine ( 3 ), neostemocochinine ( 4 ), and isoneostemocochinine ( 5 ), together with six known alkaloids. Their structures were established on the basis of extensive 1D‐ and 2D‐NMR analyses in combination with HR‐MS experiments.     

Alkaloids from the Roots of Saccopetalum prolificum

In recent years, an increased interest in the phytochemistry of the Annonaceae has beensparked by the isolation of the antileukemic Annonaceous acetogenin'. Saccopela/umprolificllm (Chun el How) Tsiang (Allnonaceae) is an evergreen tree distributed inHainan Province, P. R. China. The ethanolic extract of the plant exhibited cell growthinhibitory activity (20 ig/ml) against LIZ10 lymphocytic leukemia. A new alkaloid,prolifine (l), was isolated from the roots of S. proldicum, in addition t…