Dong-Mei Fang

Brevianamide J, A New Indole Alkaloid Dimer from Fungus Aspergillus versicolor

Brevianamide J (1), a new indole alkaloid dimer, was isolated together with four new diketopiperazine alkaloids (brevianamide K-N, 2-5) from the solid-state fermented culture of Aspergillus versicolor. Their structures were elucidated on the basis of spectral data. X-ray crystallographic analysis confirmed the structures of 1 and 4.

Analysis of mexicanolide- and phragmalin-type limonoids from Heynea trijuga using high-performance liquid chromatography/electrospray tandem mass spectrometry.

RATIONALE Limonoids, a class of tetranortriterpenoids, exhibit various biological effects, including acting as potent antifeedants and insect growth-regulators against various pests. The analysis of phragmalin- and mexicanolide-type limonoids by collision-induced dissociation tandem mass spectrometry (CID-MS/MS) has not been reported. METHODS A high-performance liquid chromatography/electrospray ionization (HPLC/ESI)-MS/MS method was developed to investigate the fragmentation patterns of [M+NH4 ](+) ions for nine reference phragmalin- and mexicanolide-type limonoids. The method was also used in the identification of limonoid compounds in botanic extracts of Heynea trijuga. RESULTS The losses of side chains and the furan part were the major fragmentation patterns. However, there was variation in the relative abundances of product ions resulting from the same fragmentation pathways. A total of 89 phragmalin- and mexicanolide-type limonoids in botanic extracts of Heynea trijuga were detected and 50 of these compounds were identified or tentatively characterized based on elemental constituents, fragmentation pathways, and the profile of the major product ions of reference compounds. In addition, the isomers could be tentatively distinguished. CONCLUSIONS An HPLC/ESI-MS/MS method was developed and could be used to simultaneously identify and screen phragmalin- and mexicanolide-type limonoids in botanic extracts of Heynea trijuga.

Different mechanism of two-proton emission from proton-rich nuclei 23 Al and 22 Mg

Two-proton relative momentum (q(pp)) and opening angle (theta(pp)) distributions from the three-body decay of two excited proton-rich nuclei, namely Al-23 --> p + p + Na-21 and Mg-22 --> p + p + Ne-20, have been measured with the projectile fragment separator (RIPS) at the RIKEN RI Beam Factory. An evident peak at q(pp) similar to 20 MeV/c as well as a peak in theta(pp) around 30 degrees are seen in the two-proton break-up channel from a highly-excited Mg-22. In contrast, such peaks are absent for the Al-23 case. It is concluded that the two-proton emission mechanism of excited Mg-22 is quite different from the Al-23 case, with the former having a favorable diproton emission component at a highly excited state and the latter dominated by the sequential decay process

Lathyrol Diterpenes as Modulators of P-Glycoprotein Dependent Multidrug Resistance: Structure–Activity Relationship Studies on Euphorbia Factor L3 Derivatives

Five series of 37 new acylate and epoxide derivatives (3-39) of Euphorbia factor L3, a lathyrol diterpene isolated from Euphorbia lathyris, were designed by modifying the hydroxyl moiety of C-3, C-5, or C-15. Chemoreversal effects of the acylates on multidrug resistance (MDR) were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein (P-gp). Eight derivatives exhibited greater chemoreversal ability than verapamil (VRP) against adriamycin (ADR) resistance. Compounds 19 and 25 exhibited 4.8 and 4.0 times, respectively, more effective reversal ability than VRP against ADR resistance. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to MDR reversal, we conducted a structure-activity relationship study of these compounds. The simulation studies indicated different possible mechanisms and revealed the important influence of hydrophobic interactions and hydrogen bonds in the flexible cavity of P-gp.

Analysis of phenolic glycosides from Ilex litseaefolia using electrospray ionization quadrupole time-of-flight mass spectrometry.

Figure 1. Phenolic glycosides: 3-hydroxy-4-O-b-D-(6-Oacetylglucopyranosyl)benzyl vanilloate (litseaefoloside A (1), Mr 494.1424); 3-hydroxy-4-O-b-Dglucopyranosylbenzyl vanilloate (vanilloylcalleryanin (2), Mr 452.1319); 4-O-b-Dglucopyranosylbenzyl vanilloate (3, Mr 436.1369); 3-hydroxy4-O-b-D-(6-O-caffeoylglucopyranosyl)benzyl vanilloate (litseaefoloside C (4), Mr 614.1636); 3-hydroxy-4-O-b-D-(6-Ovanilloylglucopyranosyl)benzyl vanilloate (litseaefoloside D (5), Mr 602.1636); 4-O-b-D-(6-O-vanilloylglucopyranosyl)vanillic acid (6, Mr 480.1268). Dear Editor,

Analysis of caffeic acid derivatives from Osmanthus yunnanensis using electrospray ionization quadrupole time-of-flight mass spectrometry.

A series of six caffeic acid derivatives (1–6) in Osmanthus yunnanensis were investigated by electrospray quadrupole time-of-flight tandem mass spectrometry (ESI-QToF-MS/MS) in both negative- and positive-ion modes. High-quality MS/MS spectra of [M + H]+ are generated from high-abundance protonated parent ions obtained by addition of ammonium chloride to the solutions. Fragmentation mechanisms of [M – H]− and [M + H]+ precursor ions were proposed and elemental compositions of most of the product ions were confirmed on the basis of the high-resolution ESI-collision-induced dissociation (CID)-MS/MS spectra. It was found that the fragment ions at m/z 179, m/z 161, m/z 135 and m/z 134 in negative-ion mode and at m/z 163, m/z 145 and m/z 135 in positive mode should be the characteristic ions of caffeic acid. In addition, the radical fragment ions with high abundance were observed for many caffeic acid derivatives especially for 4. The structural elements of unknown compounds 7 and 8 were tentatively identified on based on tandem mass spectra of known ones.

Analysis of iridoid glucosides from Paederia scandens using HPLC-ESI-MS/MS

Iridoid glycosides are an important class of natural products and have many biological activities. Iridoid glucosides in an extract of the plant species Paederia scandens were investigated using reversed-phase high performance liquid chromatography and electrospray quadrupole time-of-flight-type tandem mass spectrometry. The elemental composition of most of the compounds was determined by accurate mass and relative isotopic abundance (RIA) measurements. In positive ion mode, the fragmentation of [M+NH4](+) precursor ions was carried out using low energy collision-induced electrospray ionization tandem spectrometry. The neutral losses of NH3, H2O, Glc, and the side chain of the iridoid moiety were the main fragmentation patterns observed. For simple iridoid glycosides, the main differences were related to the side chains. Fragmentation of the [M-H](-)precursor ions was achieved for the compounds possibly having phenolic acid group. The connection order of the iridoid, sugar, and phenolic acid moieties, and the linkage of the 6-OH group of the sugar to the phenolic acid were unambiguously confirmed using a combination of MS/MS spectra in both positive and negative ion modes, and our previous work. For some trace dimeric iridoid glucosides, the connection order between the asperuloside and paederoside moieties was determined by the characteristic product ions; this was supported by D-labeling experiments. A total of 24 iridoid glucosides, including 14 new species, were identified or tentatively characterized based on exact mass, RIA values, tandem mass spectra, and D-labeling experiments.

Analysis of cipadesin limonoids from Cipadessa cinerascens using electrospray ionization quadrupole time-of-flight tandem mass spectrometry and quantum chemical calculations

RATIONALE Limonoids, a class of tetranortriterpenoids, exhibit various biological effects, such as insect antifeedant and growth regulating activities, antimicrobial activity, potent cell adhesion inhibitory effects, antimalarial activity, anticancer activities, and antioxidant activity. The potential application brings the need for reliable, fast and low-cost analysis of this class of compounds. METHODS Six cipadesin limonoids (1-6), including a pairs of isomers, from leaves and barks of Cipadessa cinerascens were investigated by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in positive-ion mode. Characteristic processes were further studied by theoretical calculations. RESULTS 1,3-Hydrogen rearrangement might play a significant role in the cleavage of -O- bridge bond in ring B and further produces some characteristic ions. For [M + Na](+) precursor ions, the product ion at m/z 133 might indicate the structure of ring A and the losses of CO(2) and AcOH occur readily. Interestingly, the radical product ion at m/z 460 from [M + Na](+) ions seems to be the characteristic ion for compound 1. A deuterium-labeling experiment supported the processes forming the radical ion. For [M + NH(4)](+) ions, high-abundance product ions resulting from sequential loss of AcOH can be observed. In addition, a pairs of isomers was unambiguously differentiated based on MS or MS/MS spectra. CONCLUSIONS In summary, sufficient information obtained from fragmentation experiments of [M + Na](+), [M + NH(4)](+) or [M + H](+) precursor ions is especially valuable for rapid identification of these limonoids or their metabolites in complex mixtures. The high-abundance radical product ion is of scientific interest.

Unexpected [M-H + Na](+.) radical ions in 3-isothiocyanato oxindoles detected by electrospray mass spectrometry

Oxindole scaffolds are versatile and useful building blocks, and commonly present in a wide variety of structurally complex and biologically active compounds, which were proved to have potent antimicrobial, antitumor and oviposition-stimulant biological activities. For the significance of those interesting molecules, numerous methods were made to construct these molecules. Among them, 3-substituted oxindoles were widely used as donors in many asymmetric strategies, such as Michael additions, Mannich reaction and D-A reaction. Recently, 3-isothiocyanato oxindoles were designed by Yuan’s group, which were applied to react with ketone with high reactivities. [10,11] Matsunaga’ group also reported that 3-isothiocyanato oxindoles exhibited high reactivities with imine. The high reactivity might indicate special character of 3-isothiocyanato oxindoles. Structural characterization is the key to further development of their functions. Herein, 3-isothiocyanato oxindoles were studied with electrospray ionization mass spectrometry (ESI-MS) in our laboratory. ESI is a soft ionization mode. It will not destroy the molecules, even the thermally unstable intermediates. The regular ions generated by electrospray quadrupole time-of-flight MS (ESI-QTOF-MS) in positive-ion mode are protonated ions, other ionic adducts including [M+Na] and [M+K]. For few compounds, odd-electron ions might be observed as M or M during ESI. In our study, a series of unexpected radical ions, [M-H+Na]•, were detected. HPLC grade acetonitrile and CD3OD were purchased from Fisher Scientific (Pittsburgh, PA) and Cambridge Isotope Laboratories (Andover, MA), respectively. MS experiments were performed on a Bruker micrOTOF-Q mass spectrometer (Bremen, Germany). The mass resolution was 10 000 FWHM at 922 u. Argon gas was used as the collision gas and high-purity nitrogen gas as the nebulizer and dry gas. The ESI source conditions were as follows: capillary V, 4500 V, end plate voltage, 4000 V; capillary exit voltage, 120 V and dry gas temperature, 180 C. The 3-isothiocyanato oxindoles were synthesized in Yuan’s laboratory. The samples with the concentration of 10 ng/ml introduction rate was 180 ml/h. Mass data were processed using Bruker Compass DataAnalysis 4.0. Theoretical calculations were performed on the bond dissociation energy (BDE) of C–H bond homolithic cleavage for the tested substrates by the hybrid density

Electrospray mass spectrometry and tandem mass spectrometry of bimetallic oxovanadium complexes

A series of six bimetallic oxovanadium complexes (1–6; only one was purified) were investigated by electrospray quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in negative-ion mode. Radical molecular anions [M]·− were observed in MS mode. Fragmentation patterns of [M]·− were proposed, and elemental compositions of most of the product ions were confirmed on the basis of the high-resolution ESI-CID-MS/MS spectra. A complicated series of low-abundance product ions similar to electron impact (EI) ionization spectra indicated the radical character of the precursor ions. Fragment ions at m/z 214, 200, and 182 seem to be the characteristic ions of bimetallic oxovanadium complexes. These ions implied the presence of a V-O-V bridge bond, which might contribute to stabilization of the radical. To obtain more information for structural elucidation, three representative bimetallic oxovanadium complexes (1–3) were analyzed further by MS in positive-ion mode. Positive-ion ESI-MS produced adduct ions of [M + H]+, [M + Na]+, and [M + K]+. The fragmentation patterns of [M + Na]+ were different than those of radical molecular anions [M]·−. Relatively simple fragmentation occurred for [M + Na]+, possibly due to even-electron ion character. Negative-ion MS and MS/MS spectra of the hydrolysis product of Complex 1 supported these finding, in particular, the existence of a V-O-V bridge bond.