Lignans and diterpenes of three Aristolochia species

Phytochemical examination of Aristolochia cymbifera, A. esperanzae and A. galeata led to the isolation of furofuran and dibenzylbutyrolactone type lignans, as well as of clerodane and ent-labdane type diterpenes. Structural assignments for two new ent-labdans are presented and discussed. © 1988.

Ditregra - An auxiliary program for structural determination of diterpenes

This work describes the creation of heuristics rules based on 13C-NMR spectroscopy that characterize several skeletal types of diterpenes. Using a collection of 2745 spectra we built a database linked to the expert system SISTEMAT. Several programs were applied to the database in order to discover characteristic signals that identify with a good performance, a large diversity of skeletal types. The heuristic approach used was able to differentiate groups of skeletons based firstly on the number of primary, secondary, tertiary and quaternary carbons, and secondly the program searches, for each group, if there are ranges of chemical shifts that identifies specific skeletal type. The program was checked with 100 new structures recently published and was able to identify the correct skeleton in 65 of the studied cases. When the skeleton has several hundreds of compounds, for example, the labdanes, the program employs the concept of subskeletal, and does not classify in the same group labdanes with double bounds at different positions. The chemical shift ranges for each subskeletal types and the structures of all skeletal types are given. The consultation program can be obtained from the authors. © 1997 - IOS Press. All rights reserved.

Fungal Transformation and Schistosomicidal Effects of Pimaradienoic Acid

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 mu M. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

New cassane butenolide hemiketal diterpenes from the marine creeper Caesalpinia honduc and their antiproliferative activity

Two new cassane butenolides, caesalpinolide A (1) and B (2), epimeric at the hemiketal position were isolated from the marine creeper Caesalpinia bonduc. The structures were elucidated by the analysis of spectroscopic data and relative stereochemistry was assigned on the basis of ROESY correlations. Compounds 1 and 2 were found to inhibit MCF-7 breast cancer cell lines with ICso values of (IlM)12.8 and 6.1, respectively, along with the inhibition of endometrial and cervical cancer cell lines

Spongian Diterpenes from Australian nudibranchs: An anatomically guided chemical study of Glossodoris atromarginata

An Australian population of the nudibranch mollusk Glossodoris atromarginata has been found to contain furanoditerpenes of the spongian series. Spongia-13(16),14-dien-3-one (1) and 3 beta-acetoxy-19-hydroxyspongia-13(16),14-dien-2-one (2) were isolated for the first time from a natural source, along with a series of known diterpenes (3-7). Anatomical dissection of the animals revealed the relative distribution and chemical variation of secondary metabolites. Structural studies have provided a basis for chemical comparisons between populations from different geographic locations.

Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol

The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-θ, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes α, μ, and π was studied with affnity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes α, μ, and π but also of enhancing UDGPT and GST-θ. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase II detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.

Daphnane- and Tigliane-Type Diterpenoid Esters and Orthoesters from Pimelea elongata.

Investigation of Pimelea elongata ("Lakebed Pimelea") afforded 18 tigliane- and daphnane-type diterpenes (1-18). Eight of these were new compounds: four (1-3, 5) tigliane esters and four (7, 8, 10, 11) daphnane orthoesters. The 10 known compounds were 12-O-decanoylphorbol-13-acetate (4), P. simplex subtoxin B (6), wikstroelide E (9), pimelotides A and B (12, 13), gnidiglaucin (14), simplexin (15), huratoxin (16), kirkinine D (17), and 12-beta-acetoxyhuratoxin (18). The structures and relative configurations of the new compounds were determined by ID and 2D NMR spectroscopic studies in combination with MS analyses.

Enantiospecific synthesis of the tricyclic core structure of lippifolianes

An enantiospecific synthesis of the [6.6.3]-tricyclic carbon framework, 2,6,6,9-tetra-methyltricyclo[5.4.0.02,4]undecane, present in the sesquiterpenes lippifolianes and the diterpenes cyclosclareol, metasequoic acids and parguerols, starting from the readily available monoterpene (R)-carvone, is described.

Diterpenoids of Roylea calycina(Roxb.) Briq.

The structures of three new diterpenes, calyone, calyenone, and precalyone, isolated from the aerial portion of Roylea calycina have been shown to be 3-acetoxy-15,16-epoxy-9-hydroxylabda-1 3(16),14-dien-7-one (2), 3-acetoxy-15,16-epoxylabda-8,13(16),14-trien-7-one (5), and 3-acetoxy-9,13;15,16-diepoxylabda-14-en-7-one (7), respectively, by chemical and spectroscopic studies. Precalyone showed antitumor activity against P-388 lymphocytic leukaemia.

An Enantiospecific Approach to the 5-8-5 Tricyclic System of Basmanes

An enantiospecific synthesis of the 5-8-5 tricyclic ring system present in the basmane diterpenes has been accomplished, starting from ethyl 3-isopropyl-2-methylene-1-methylcyclopentane-acetate readily available in five steps from (R)-limonene] employing an RCM reaction for the annulation of cyclooctane and an intramolecular rhodium carbenoid CH insertion reaction for the construction of the cyclopentane ring.

A unified strategy to ent-kauranoid natural products : total syntheses of (–)-maoecrystal Z, (–)-trichorabdal A, and (–)-longikaurin E

The diterpenoid constituents of the Isodon plants have attracted reasearchers interested in both their chemical structures and biological properties for more than a half-century. In recent years, the isolations of new members displaying previously unprecedented ring systems and highly selective biological properties have piqued interest from the synthetic community in this class of natural products.

Reported herein is the first total synthesis of such a recently isolated diterpenoid, (–)-maoecrystal Z. The principal transformations implemented in this synthesis include two highly diastereoselective radical cyclization reactions: a Sm^(II)-mediated reductive cascade cyclization, which forms two rings and establishes four new stereocenters in a single step, and a Ti^(III)-mediated reductive epoxide-acrylate coupling that yields a functionalized spirolactone product, which forms a core bicycle of maoecrystal Z.

The preparation of two additional ent-kauranoid natural products, (–)-trichorabdal A and (–)-longikaurin E, is also described from a derivative of this key spirolactone. These syntheses are additionally enabled by the palladium-mediated oxidative cyclization reaction of a silyl ketene acetal precursor that is used to install the bridgehead all-carbon quaternary stereocenter and bicyclo[3.2.1]octane present in each natural product. These studies have established a synthetic relationship among three architecturally distinct ent-kaurane diterpenoids and have forged a path for the preparation of interesting unnatural ent-kauranoid structural analogs for more thorough biological study.

天然产物Standishinal 的首次全合成研究

具有1，1，4α-三甲基氢化芴骨架结构的天然三环二萜化合物自然界中不常见。在该类化合物中，Standishinal 具有良好的芳香化酶抑制活性和细胞毒活性。迄今未发现有Standishinal 的全合成报道，因此，我们对Standishinal 的全合成进行了探索，在该过程中得到以下实验结果： 1. 发现MSA/P2O5、MSA 在无溶剂条件下，25 °C 时烷氧基苯即可实现向苯酚的转化，但在CH3NO2 中，温度升高至80 °C 并未发生反应。 2. 烷氧基苯或对溴苯酚与α-环香叶酸在不同温度下以MSA/P2O5、MSA、PPA为催化剂以CH3NO2 为溶剂或以BF3·Et2O为催化剂时均不发生Friedel-Crafts酰化反应。 3. 对溴苯酚与香叶酸在p-TsOH 催化作用下发生了香叶酸向α-环香叶酸环化、α-环香叶酸环与对溴苯酚的酯化，得到了唯一产物α-环香叶酸对溴苯酯，产率68%。 Standishinal is one of tricyclic-diterpenes possessing the uncommon 1, 1,4a-trimethylhydrofluorene skeleton. Standishinal possesses cytotoxic and aromataseinhibitory activities. Till now, no synthesis of standishinal has been reported. Inattempt to synthesize standishinal, the following phenomenon were observed: 1. Alkyloxybenzenes could be transformed into corresponding phenol at 25 °C inthe presence of MSA/P2O5 or MSA under solvent free condition. ButAlkyloxybenzenes are stable in presence of MSA/P2O5 or MSA in CH3NO2 even at 80 °C. 2. Friedel-Crafts acylation of alkyloxybenzenes and p-bromophenol withα-cyclogeranic acid could not be realized under catalysis of MSA/P2O5, MSA or PPAin CH3NO2, or under catalysis of BF3·Et2O without CH3NO2. 3. The reaction of 4-bromaophenol and geranic acid in the presecnce of p-TsOHafforded 4-bromophenol α-cyclogeranoate in which cyclization of geranic acid toα-cyclogeranic acid was followed by esterification of α-cyclogeranic acid with p-bromophenol.