Synthesis and Crystal Structure of a Novel 14,20-Annulated Pentacyclic Steroid 17(S)-Methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one

The title compound 17(S)-methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one was synthesized by an improved tandem reaction, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 10.55248(15), b = 12.14700(16), c = 14.56841(18) ?, V = 1867.39(4) ?3, Z = 4, Dc= 1.175 g/cm3, μ= 0.604 mm-1, F(000) = 720, the final R = 0.0400 and w R = 0.1072 for 3610 observed reflections with I 2σ(I).     

α- and β-Mercaptoalkanoic Acids: Versatile Synthons in the Syntheses of Thiasteroid Analogues and Selenathiadiazoles

This review describes the reactions of α/β-mercaptoalkanoic acids as building blocks for the synthesis of heterosteroids, polyfunctional heterocycles with pharmacological interest. Annelated heterocycles have been prepared by the cyclocondensation reaction of α- and β-mercaptoalkanoic acids with carbonyl compounds. This reaction takes place by nucleophilic addition, followed by cyclization with elimination of water. The main objective of this survey is to provide a comprehensive account of this reaction type in building various heterocycles, and examining their potential in developing better chemotherapeutic agents.     

The Occurrence and Biological Activity of Tormentic Acid—A Review

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.     

Pentacyclic triterpenes from <Emphasis Type="Italic">Sarcostemma clausum</Emphasis>

A homologous series of alkanoic acid (C₂–C₅) esters of germanicol was isolated from the methanolic extract of Sarcostemma clausum, of which germanicol-3-propionate and 3-pentanoate have not been previously described in the literature. In addition, taraxasterol, multiflorenol, and bauerenol were also isolated for the first time from the genus Sarcostemma. Structures were elucidated by chemical and spectroscopic methods (NMR, IR, SM) and by comparison with literature data.Published in Khimiya Prirodnykh Soedinenii, No. 6 pp. 464–466, November–December, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Unusual molecular pattern in Ajugoideae subfamily: the case of Ajuga genevensis L. from Dolomites

We analysed the ethanolic extract from Ajuga genevensis L. (Lamiaceae) growing in Dolomites, part of Italian Alps. Three new compounds for this species were identified: rosmarinic acid (1), oleanolic acid (2) and maslinic acid (3), representative of two different classes of chemical compounds (phenylpropanoids and pentacyclic triterpenes). A. genevensis resulted to be a valuable source of these compounds endowed with interesting biological activities (i.e. antioxidant, neuroprotective, anti-inflammatory, antiproliferative). The recognition of compounds (1), (2) and (3) may also confirm the ethnomedicinal uses of this plant. From a chemotaxonomical point of view, it is worth noting that iridoids were not evidenced in this accession. Iridoids are considered chemotaxonomic marker in Lamiales, and, in contrast with a previous study on this species, the presence of aucubin was not confirmed. In addition, the presence of large amounts of rosmarinic acid (1) was unexpected for a species that does not belong to subfamily Nepetoideae.     

NMR spectral assignment of 2α- and 3β-methylhopanes and evidence for boat conformation in D ring of 17α(H),21α(H)-hopanes

The full (1)H and (13)C NMR chemical shift assignment of 2α-methyl-17α(H),21β(H)-hopane is presented. This compound is formed in mature sediments from biogenic sources of 2β-methyl-17β(H),21β(H)-hopanoids, which include several cyanobacteria. In addition, full (1)H and (13)C NMR chemical shift data of all four 17,21 isomers of 3β-methylhopane have been assigned. The thermodynamically most stable 3β-configuration corresponds to that found in bacterial sources. The data presented here suggest minor corrections to the (13)C chemical assignments reported earlier for 17α(H)-hopanes. Moreover, spectral evidence indicates an unexpected ring-D boat conformation of 17α(H),21α(H)-hopanes, which may serve to explain the steric strain reported for this isomer.     

β-Isothiocyanatoketones: A Convenient Source of Heterocyclic Compounds

Summary. The preparation of -isothiocyanatoketones and their reactions leading to formation of pyrimidine and bicyclic, tricyclic, tetracyclic, and pentacyclic heterocyclic compounds are reviewed. A few references concerning the rearrangement of heterocyclic compounds are also included. Some of the compounds reported have shown good antiinflammatory activity.     

3β-Methoxyolean-18-ene (miliacin) from the marine fungus Chaetomium olivaceum

A pentacyclic tritepenoid, 3-methoxyolean-18-ene (miliacin), was isolated for the first time from the marine fungus Chaetomium olivaceum. Its structure was determined on the basis of 2D NMR spectroscopy and X-ray diffraction data.     

1H and 13C assignments of two new triterpenes from Cladocolea grahami

The structure elucidation and 1H and 13C assignments of the new triterpenes 3beta-palmitoxy-7beta-hydroxyolean-12-ene (1) and its hydrolysis product 3beta,7beta-dihydroxyolean-12-ene (2) and 3beta-sn-glyceroyl-(1'-palmitoxy)urs-12-ene (3), isolated from the aerial parts of Cladocolea grahami (Loranthaceae), are reported.     

Capturing a Pentacyclic Fragment-Based Library Derived from Perophoramidine: Their Design,Synthesis and Evaluation as Anticancer Compounds by DNA Double-Strand Breaks (DSB) and PARP-1 Inhibition

Herein we have reported the discovery of a pentacyclic building block comprised of fused indole-quinoline and piperidinone from the natural product perophoramidine as a formidable anticancer agent. The compounds were synthesized in six steps where the key steps involved a blue LED mediated intramolecular cyclopropanation of the indole intermediates and concomitant reduction of the associated aryl nitro moiety to nitroso in the molecule. Cytotoxicity screening of the compounds against an array of cancer cells that is, MCF7, HCT116 and A549 demonstrated 0.6 to 9 μM IC₅₀s by few of the compounds. γH2AX immunofluorescence assay of the two most potent molecules from the phenotypic screening with anti-γ-H2AX Alexa Fluor 488 antibody revealed extensive DNA damage of the A549 cells which indicated probable PARP inhibition (similar to Perophoramidine). Through molecular docking and molecular dynamic (MD) simulation studies the binding efficiency of our compounds with poly(ADP-ribose)polymerase 1 (PARP 1) enzyme was determined. Chemiluminescent PARP Assay with Histone-coated strips indicated that the most active compounds from the phenotypic screening induced PARP-1 inhibition with IC₅₀s of 1.3→1.5 μM.