Indole alkaloid

About: Indole alkaloid is a research topic. Over the lifetime, 868 publications have been published within this topic receiving 15401 citations. The topic is also known as: indole alkaloids.

Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids.

Abstract: We demonstrated here a series of Aspidosperma terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (e.g., with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of Aspidosperma terpenoid alkaloid therapeutics. Furthermore, this synthetic approach features late-stage facile derivatization on complex natural product molecules, providing a versatile path to indole derivatization of this family of alkaloids with diverse chemical functionalities for future medicinal chemistry and chemical biology discoveries.

An indole diketopiperazine alkaloid and a bisabolane sesquiterpenoid with unprecedented skeletons from Aspergillus fumigatus.

Abstract: Fumitryprostatin A (1), the first example of an indole diketopiperazine alkaloid with a tricyclic 5/6/5 skeleton characterized by a dipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-dione ring system decorated with a prenylated indole moiety, and fuminoid A (2), a sesquiterpenoid with a bicyclo[3.2.1]octane ring featuring a novel carbon skeleton via the transformation of the methyl, were isolated from the fungus Aspergillus fumigatus along with six known diketopiperazine alkaloids. The structure with the absolute configuration of 1 was determined based on spectroscopic analyses and X-ray crystallographic analysis, while the configuration of 2 was assigned tentatively by 13C NMR data with DP4+ probability analyses and ECD calculations. A plausible biosynthetic pathway for 1 was proposed starting from L-Trp and L-Pro via normal indole diketopiperazine. Compound 1 exhibited moderate cytotoxic activity with an IC50 value of 14.6 μM, while compound 8 exhibited moderate immunosuppressive activity in vitro.

Indole Alkaloids from the Leaves of Rauvolfia yunnanensis

Abstract: Rauvolfia yunnanensis Tsiang are commonly used as a folklore herb to treat hypertension,snake bites,and insanity in the southwest of China,and an important industrial raw material of reserpine and verticalBut the wild resources of it reduced gradually in recent years,thus we have introduced and cultivated it to the arid-hot valley region of Yunnan Province,China,and investigated the chemical constituents variety of it for the sustainable utilizationThe dried leaves powder(80 kg) of Ryunnanensis was extracted with 95%(volume fraction) EtOH(40 L×5,8 h each) ,and led to the isolation of eleven indole alkaloids by column chromatography(silica,alumina and Sephadex LH-20 gel) methodsTheir structures were identified as 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) by spectral analysis(UV,IR,MS and 1D,2D NMR) ,respectivelyAmong them,compound 2 was a new indole alkaloids,compounds 1,8 and 9 were firstly isolated from this plant

Functional Characterization of Monoterpenoid Indole Alkaloid (MIA) Biosynthetic Genes in Catharanthus roseus

Abstract: The monoterpenoid indole alkaloids (MIAs) of Madagascar periwinkle (Catharanthus roseus) are known to be among the most important source of natural drugs used in various cancer chemotherapies. MIAs are derived by combining the iridoid secologanin with tryptamine to form the central precursor strictosidine that is then converted to most known MIAs, such as catharanthine and vindoline that dimerize to form anticancer vinblastine and vincristine. While their assembly is still poorly understood, the complex multistep pathways involved occur in several specialized cell types within leaves that are regulated by developmental and environmental cues. The organization of MIA pathways is also coupled to secretory mechanisms that allow the accumulation of catharanthine in the waxy leaf surface, separated from vindoline found within leaf cells. While the spatial separation of catharanthine and vindoline provides an explanation for the low levels of dimeric MIAs found in the plants, the secretion of catharanthine to the leaf surface is shown to be part of plant defense mechanisms against fungal infection and insect herbivores. The transcriptomic databases of Catharanthus roseus and various MIA producing plants are facilitating bioinformatic approaches to identify novel MIA biosynthetic genes. Virus-induced gene silencing (VIGS) is being used to screen these candidate genes for their involvement in iridoid biosynthesis pathway, especially in the identification of 7-deoxyloganic acid 7-hydroxylase (CrDL7H) shown by the accumulation of its substrate, 7-deoxyloganic acid and decreased level of secologanin along with catharanthine and vindoline. VIGS can also confirm the biochemical function of genes being identified, such as in the glucosylation of 7-deoxyloganetic acid by CrUGT8 shown by decreased level of secologanin and MIAs within silenced plants. Silencing of other iridoid biosynthetic genes, loganic acid O-methyltransferase (LAMT) and secologanin synthase (SLS) also confirm the metabolic route for iridoid biosynthesis in planta through 7-deoxyloganic acid, loganic acid, and loganin intermediates. This route is validated by high substrate specificity of CrUGT8 for 7-deoxyloganetic acid and CrDL7H for 7-deoxyloganic acid. Further localization studies of CrUGT8 and CrDL7H also show that these genes are preferentially expressed within Catharanthus leaves rather than in epidermal cells where the last two steps of secologanin biosynthesis occur.

The First Enantiospecific Total Synthesis of a C-Quaternary Voachalotine Alkaloid, (+)-Dehydrovoachalotine.

Abstract: The first enantiospecific total synthesis of the indole alkaloid (+)-dehydrovoachalotine ( 1 ) has been achieved from d -(+)-tryptophan methyl ester in 28% overall yield. The formation of the prochiral quaternary carbon center at C-16 in the key intermediate ( 12 ) was realized via a Tollens reaction from N a -methylvellosimine ( 13 ) in 95% yield. This approach could also be applied to the synthesis of many other indole alkaloids that contain a quaternary carbon center at C(16).