Five new isocoumarins from Sonoran desert plant-associated fungal strains Paraphaeosphaeria quadriseptata and Chaetomium chiversii

Five new isocoumarins, paraphaeosphaerins A-C and chaetochiversins A and B, biogenetically related to monocillin I and radicicol, have been isolated from solid agar cultures of Paraphaeosphaeria quadriseptata and Chaetomium chiversii, two fungal strains living in association with the Sonoran desert plants, Opuntia leptocaulis and Ephedra fasciculata, respectively. A new chroman-4-one, aposphaerin C, was also isolated from P. quadriseptata. Their structures and stereochemistry were elucidated using a combination of ¹H and ¹³C homo- and hetero-nuclear 2D NMR techniques, ¹H NMR analysis of Mosher's esters, and chemical correlations.     

Daphcalycinosidines A and B, new iridoid-alkaloids from Daphniphyllum calycinum

Three new alkaloids, daphcalycinosidines A (1) and B (2) and daphcalycic acid (3) have been isolated from the seeds of Daphniphyllum calycinum. The structures and relative stereochemistries were determined on the basis of spectral studies including 2D NMR, mass spectrometry and chemical transformations. Structures 1 and 2 are characterized by an iridoid glucoside moiety linked to new Daphniphyllum alkaloid moieties.     

Bis-cephalezomines A-E from Cephalotaxus harringtonia var. nana

Five new dimeric Cephalotaxus alkaloids, bis-cephalezomines A-E (1-5), have been isolated from the leaves of Cephalotaxus harringtonia var. nana, and the structures and stereochemistry were elucidated on the basis of spectroscopic data including 2D NMR and FABMS/MS spectra, and chemical means.     

Hamigeromycins C-G, 14-membered macrolides from the fungus Hamigera avellanea BCC 17816

Five new 14-membered macrolides, hamigeromycins C-G, together with the previously described compounds, hamigeromycin A and 89-250904-F1 (radicicol analog A), were isolated from the fungus Hamigera avellanea BCC 17816. Hamigeromycins A, C, D, and E are stereoisomers differing from one another in the absolute configurations of the 4′,5′-diol moiety. Hamigeromycins F and G are unusual 5′-keto-analogs, and they are 6′-epimers to each other. The structures and the stereochemistry of the new compounds were deduced by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria

Chemical examination of the Chinese marine sponge Xestospongia testudinaria led to the isolation of 39 new brominated polyunsaturated compounds, which were designated with the trivial names xestospongienes A-Z and Z₁-Z₁₃. The structures of these compounds were elucidated by analyzing extensive spectroscopic (IR, MS, 1D, and 2D NMR) data and the results from CD spectral assignment, chemical conversion, and Mosher reaction.     

Argeloside A and B, two novel 14,15-secopregnane glycosides from Solenostemma argel

Argeloside A and B, two novel 14,15-secopregnane glycosides characterized by the presence of two hemiketal functions involved in two five-membered rings, were isolated from Solenostemma argel fruits. Their structures have been established by ESIMS and NMR experiments. In particular the relative configuration of the molecules has been defined by combining the available NMR data with quantum chemical calculations of the geometries and ¹³C chemical shifts.     

A green protocol for efficient discovery of novel natural compounds: Characterization of new ginsenosides from the stems and leaves of Panax ginseng as a case study

Exploration of new natural compounds is of vital significance for drug discovery and development. The conventional approaches by systematic phytochemical isolation are low-efficiency and consume masses of organic solvent. This study presents an integrated strategy that combines offline comprehensive two-dimensional liquid chromatography, hybrid linear ion-trap/Orbitrap mass spectrometry, and NMR analysis (2D LC/LTQ-Orbitrap-MS/NMR), aimed to establish a green protocol for the efficient discovery of new natural molecules. A comprehensive chemical analysis of the total ginsenosides of stems and leaves of Panax ginseng (SLP), a cardiovascular disease medicine, was performed following this strategy. An offline 2D LC system was constructed with an orthogonality of 0.79 and a practical peak capacity of 11,000. The much greener UHPLC separation and LTQ-Orbitrap-MS detection by data-dependent high-energy C-trap dissociation (HCD)/dynamic exclusion were employed for separation and characterization of ginsenosides from thirteen fractionated SLP samples. Consequently, a total of 646 ginsenosides were characterized, and 427 have not been isolated from the genus of Panax L. The ginsenosides identified from SLP exhibited distinct sapogenin diversity and molecular isomerism. NMR analysis was finally employed to verify and offer complementary structural information to MS-oriented characterization. The established 2D LC/LTQ-Orbitrap-MS/NMR approach outperforms the conventional approaches in respect of significantly improved efficiency, much less use of drug materials and organic solvent. The integrated strategy enables a deep investigation on the therapeutic basis of an herbal medicine, and facilitates new compounds discovery in an efficient and environmentally friendly manner as well.     

Tricalysiolides A-F, new rearranged ent-kaurane diterpenes from Tricalysia dubia

Six rearranged ent-kaurane diterpenes, tricalysiolides A-F, having the cafestol-type carbon framework were isolated from the wood of Tricalysia dubia (Rubiaceae). Their absolute structures were determined on the basis of the 2D NMR spectroscopy, X-ray crystallographic analysis, and chemical methods.     

Cytotoxic eremophilane sesquiterpenoids from the saprobic fungus Berkleasmium nigroapicale BCC 8220

Berkleasmins A-E, five new eremophilane sesquiterpenoids were isolated from the saprobic fungus Berkleasmium nigroapicale BCC 8220. The structures of the new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometry data in combination with chemical means. Berkleasmins A and C exhibited cytotoxic activity against cancer cell-lines (NCI-H187, MCF-7, and KB) as well as nonmalignant Vero cells with IC₅₀ values of 1.1-7.5 μg/mL, and these compounds also showed antimalarial activity with respective IC₅₀ of 3.1 and 2.8 μg/mL.     

Microsporins A and B: new histone deacetylase inhibitors from the marine-derived fungus Microsporum cf. gypseum and the solid-phase synthesis of microsporin A

Two new cyclic peptides, microsporins A and B (7 and 8), were isolated from culture extracts of the marine-derived fungus Microsporum cf. gypseum obtained from a sample of the bryozoan Bugula sp. collected in the U.S. Virgin Islands. The structures of the new compounds were determined by extensive interpretation of 2D NMR data and by chemical methods. Microsporins A and B are potent inhibitors of histone deacetylase and demonstrate cytotoxic activity against human colon adenocarcinoma (HCT-116), as well as against the National Cancer Institute 60 cancer cell panel. The total synthesis of microsporin A on solid-phase is also reported.     

New pentacyclic triterpene saponins with strong anti-leishmanial activity from the leaves of Maesa balansae

Six new triterpene saponins bearing an oxygen bridge between C-13 and C-28 and with pronounced anti-leishmanial activity were isolated from the methanolic extract of leaves of the Vietnamese medicinal plant Maesa balansae. The structure was established on the basis of detailed NMR (COSY, NOESY, HMQC, HMBC, TOCSY and DEPT) and FAB-MS studies along with chemical degradation. All saponins identified contained the same pentaglycosidic side chain, but a different esterification pattern on the triterpenoid part. Biological evaluation of the individual compounds against visceral leishmaniasis (Leishmania infantum amastigotes) revealed a much better activity in vitro compared to the reference compound Pentostam^®, which is currently used as first-line treatment for leishmaniasis.     

Triterpenoids from Cedrela sinensis

Twenty-three new triterpenoids (1-23), all having an apotirucallane skeleton, were isolated from the seeds, leaves, and stems of Cedrela sinensis (Meliaceae). Their structures were determined by 2D NMR experiments, X-ray crystallographic analysis, and chemical methods. These triterpenoids showed a moderate cytotoxic activity against P-388 murine leukemia cells (IC₅₀ 0.26-9.9 μg/mL).     

Daphnezomines P, Q, R and S, new alkaloids from Daphniphyllum humile

Four new alkaloids, daphnezomines P-S (1-4), have been isolated from the fruits of Daphniphyllum humile, and the structures and the stereochemistry were elucidated on the basis of spectroscopic data including 2D NMR and MS/MS spectra, and chemical correlations. Daphnezomines P (1) and Q (2) were the first Daphniphyllum alkaloids with an iridoid glycoside moiety.     

Novel cytotoxic kaurane-type diterpenoids from the New Zealand Liverwort Jungermannia species

Novel cytotoxic rearranged kaurene- and ent-kaurene-type diterpenoids against HL-60 cells have been isolated from the unidentified New Zealand liverwort Jungermannia species together with previously known ent-kaurane-type diterpenoids. Their structures were determined by extensive NMR techniques, chemical degradation and X-ray crystallographic analysis.     

Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

Synthesis and NMR spectra of the syn and anti isomers of substituted cyclobutanes—evidence for steric and spatial hyperconjugative interactions

The syn and anti isomers of cis,cis-tricyclo[5.3.0.0^2,6]dec-3-ene derivatives have been synthesized and their ¹H and ¹³C NMR spectra unequivocally analyzed. Both their structures and their ¹H and ¹³C NMR chemical shifts were calculated by DFT, the latter two calculations employing the GIAO perturbation method. Additionally, calculated NMR shielding values were partitioned into Lewis and non-Lewis contributions from the bonds and lone pairs involved in the molecules by accompanying NBO and NCS analyses. The differences between the syn and anti isomers were evaluated with respect to steric and spatial hyperconjugation interactions.     

New diterpenes of the pseudopterane class from two closely related Pseudopterogorgia species: isolation, structural elucidation, and biological evaluation

Parallel chemical investigations of the hexane and chloroform extracts of the sea plumes Pseudopterogorgia bipinnata and Pseudopterogorgia kallos has led to the discovery of seven new diterpenoids of the pseudopterane class, namely, kallolide D (2), kallolide C acetate (3), kallolide E (4), kallolide F (5), kallolide G (6), kallolide H (7), and kallolide I (8), in addition to nine previously described compounds of the pseudopterane and gersolane families of diterpenes. The chemical structures of the new metabolites were established by 1D and 2D NMR, IR, UV, HRMS, and, in some instances, by single-crystal X-ray crystallographic analyses. Biological screening of these metabolites revealed significant anti-parasitic activity albeit marginal anti-tubercular activity.     

Formamidobisabolene-based derivatives from a sponge Axinyssa sp.

Chemical examination of a Chinese sponge Axinyssa sp. resulted in the isolation of 12 new formamidobisabolene-based analogues named axinyssines A–L (1–12), along with a new natural product (13) and three known formamidobisabolenes (14–16). Their structures were determined on the basis of extensive NMR and mass spectroscopic analyses in association with ICD data, Mosher reaction and chemical conversion for the assignment of absolute configurations. All compounds were evaluated for antitumor and antimicrobial activities.     

Synthesis of new 10,11-dihydrodibenzo[a,d]cycloheptene S-thiocarbamate derivatives via a benzylic Newman–Kwart rearrangement

New S-thiocarbamates possessing a 10,11-dihydro-5H-dibenzo[a,d]cycloheptene moiety were obtained unexpectedly in the process of preparing new O-thiocarbamates starting from 5-dibenzosuberol (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol) and aroyl-isothiocyanates. These compounds were obtained via a benzylic Newman–Kwart rearrangement mechanism. The structures of the new thiocarbamates were confirmed by elemental analysis, IR, and NMR spectroscopy and by X-ray crystallography.     

Anthracene coupled trans-pyridylcinnamide: a new fluororeceptor for selective sensing of dicarboxylates

trans-Pyridylcinnamide has been established as an alternative hydrogen bonding synthon, in place of urea for carboxylate binding. This alternative motif has been used in the design and synthesis of new fluorescent ‘On-Off’ signalling chemical sensor 1, which is found to bind aliphatic dicarboxylates with moderate binding constants. The recognition ability has been established by fluorescence, UV-vis and ¹H NMR spectroscopic methods. The receptor is found to be selective for long chain pimelate.