Vikas Bajpai

Skeletal Diverse Synthesis of N-Fused Polycyclic Heterocycles via the Sequence of Ugi-Type MCR and CuI-Catalyzed Coupling/Tandem Pictet–Spengler Reaction

Several diversity-oriented syntheses of N-fused polycyclic heterocycles have been demonstrated but most of them are based on point diversity within the same library and usually involve time-consuming sequential multistep syntheses, which also suffer from low yields and/or poor precursor scopes. We have developed a new strategy for the syntheses of skeletal diverse N-fused polycyclic compounds via an Ugi-type MCR followed by a CuI-catalyzed coupling reaction or tandem Pictet-Spengler reaction. This two-step sequence provides eight distinct skeleton of fused {6-5-5-6}, {5-5-5-6}, {6-5-6-6}, and {5-5-6-6} ring systems that have applications in medicinal chemistry and chemical genetics too.

Diversity oriented synthesis of pyran based polyfunctional stereogenic macrocyles and their conformational studies.

A new approach to synthesize a homologous series of 14-, 15-, and 16-membered drug-like, macrocyclic glycoconjugates involving TBAHS promoted azide-propenone intramolecular cycloaddition in designed C-glycopyranosyl butenones from a simple sugar d-glucose and d-mannose is reported.

Profiling of Piper betle Linn. cultivars by direct analysis in real time mass spectrometric technique.

Piper betle Linn. is a traditional plant associated with the Asian and southeast Asian cultures. Its use is also recorded in folk medicines in these regions. Several of its medicinal properties have recently been proven. Phytochemical analysis showed the presence of mainly terpenes and phenols in betel leaves. These constituents vary in the different cultivars of Piper betle. In this paper we have attempted to profile eight locally available betel cultivars using the recently developed mass spectral ionization technique of direct analysis in real time (DART). Principal component analysis has also been employed to analyze the DART MS data of these betel cultivars. The results show that the cultivars of Piper betle could be differentiated using DART MS data.

Thermally Stable Nonaggregating Pyrenylarenes for Blue Organic Light-Emitting Devices†CDRI communication No. 8097.

A new series of thermally stable blue light-emitting nonplanar pyrenylarenes having an amine donor and a nitrile acceptor group was prepared from a ketene-S,S-acetal under conventional heating and/or microwave irradiation. The photophysical, electrochemical, and optical behavior of donor-acceptor pyrenylarenes are demonstrated. The performance of blue light-emitting pyrenylarenes was investigated by fabricating a multilayer device with the device configuration of ITO/PEDOT:PSS (40 nm)/NPB (30 nm)/pyrenylarene (55 nm)/BCP (8 nm)/LiF (0.6 nm)/Al (200 nm), which exhibited low turn-on voltage (5 V) with luminance efficiency of 0.8 Cd/A with nonaggregation behavior in both solution and solid state.

Rapid profiling and structural characterization of bioactive compounds and their distribution in different parts of Berberis petiolaris Wall. ex G. Don applying hyphenated mass spectrometric techniques

RATIONALE Berberis petiolaris Wall. is a lesser known medicinal plant, belonging to the family Berberidaceae. The genus Berberis is known for many biological activities such as anti-microbial, anti-inflammatory and anti-diarrheal, etc. There are not many reports of the isolation of components from Berberis petiolaris. This study aims to seek identification, characterization and quantification of components. METHODS A method was developed for rapid screening of phytochemicals using high-pressure liquid chromatography hyphenated with quadrupole time-of-flight mass spectrometry (HPLC/ESI-QTOF-MS/MS). Suitable collision-induced dissociation mass spectrometry (CID-MS/MS) methods were developed for structural investigation of alkaloids, flavanoids and other classes of compounds using nine reference standards for authentication. Multiple reaction monitoring (MRM) methods were developed for quantitative study of five constituents using triple quadrupole-linear ion trap mass spectrometry (UPLC/QqLIT-MS/MS). RESULTS On the basis of HPLC retention behavior and fragmentation pathways obtained by high-resolution MS and MS/MS, 32 compounds were identified and characterized in different parts of Berberis petiolaris. Quantitative studies of chlorogenic acid, magnoflorine, jatrorrhizine, palmatine and berberine were also completed successfully. CONCLUSIONS Rapid and accurate HPLC/ESI-QTOF-MS/MS and UPLC/ESI-QqLIT-MS/MS methods were established for identification, characterization and quantification of phytochemicals in the ethanolic extract of Berberis petiolaris. These methods, therefore, can be used for studies on phytochemical variation in different parts of the plant. Principle components analysis (PCA) may be used for plant part discrimination.

Structural characterization of flavonoid C- and O-glycosides in an extract of Adhatoda vasica leaves by liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONALE Adhatoda vasica Nees is a well-known Ayurvedic medicinal plant, belonging to the family Acanthaceae. This study aims to seek identification and characterization of flavonoid C- and O-glycosides in the aqueous fraction of the plant leaves. METHODS A method was developed for simultaneous characterization of flavonoids and their glycosides using high-pressure liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC/ESI-QTOF-MS/MS). The chromatographic separation was carried on an Agilent Poroshell 120 EC-C18 column (4.6 × 150 mm, 2.7 µm) operated with 0.1% formic acid aqueous solution and methanol as the mobile phase. RESULTS The fragmentations of the studied [M-H](-) ions of C-glycosides were shown to be cross-ring cleavages of the glycoside moiety [M-H-(60/90/120)](-) whereas O-glycosides were shown to eliminate the sugar moiety (Y0 (-) or [Y0 -H](-) ) from the aglycone unit; 6-C-glycosides exhibited [M-H-18](-) , a characteristic ion, and also a higher abundance of (0,3) X6 or 8 ions in comparison to 8-C glycosides; flavonoid 6,8-di-C-glycosides exhibited cross-ring cleavages of the sugar attached to the C-6 position preferentially. CONCLUSIONS This method was successfully applied for analysis of flavonoids and their glycosides in Adhatoda vasica leaves. A total of 29 compounds were tentatively identified including 17 C-, nine O-glycosides and three flavonoids.

Characteristic differences in metabolite profile in male and female plants of dioecious Piper betle L.

Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in the subtropics. Therefore, due to lack of flowering, gender distinction cannot be made the in the subtropics. Gender distinction in P. betle in vegetative state can be made using Direct Analysis in Real Time Mass Spectroscopy (DARTMS), a robust high-throughput method. DARTMS analysis of leaf samples of two male and six female plants showed characteristic differences in the spectra between male and female plants. Semi-quantitative differences in some of the identified peaks in male and female landraces showed gender-based differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235 and 252 showed two distinct clusters of male and female landraces. It appears that male and female plants besides having flowers of different sexes also have characteristic differences in the metabolites representing two metabolic types.

Analysis of phytochemical variations in dioecious Tinospora cordifolia stems using HPLC/QTOF MS/MS and UPLC/QqQLIT-MS/MS

INTRODUCTION The stem of dioecious Tinospora cordifolia (Menispermaceae) is a commonly used traditional Ayurvedic medicine in India having several therapeutic properties. OBJECTIVE To develop and validate LC-MS methods for the identification and simultaneous quantitation of various secondary metabolites and to study metabolomic variations in the stem of male and female plants. METHODS Ethanolic extract of stems were analysed by HPLC/ESI-QTOF-MS/MS for rapid screening of bioactive phytochemicals. High resolution MS and MS/MS in positive ESI mode were used for structural investigation of secondary metabolites. An UPLC/ESI-QqQ(LIT) -MS/MS method in MRM mode was developed and validated for the simultaneous quantitation of five bioactive alkaloids. RESULTS Identification and characterisation of 36 metabolites including alkaloids, sesquiterpenes and phytoecdysteroids were performed using LC-MS and MS/MS techniques. The bioactive alkaloids such as jatrorrhizine, magnoflorine, isocorydine, palmatine and tetrahydropalmatine were successfully quantified in male and female plants. The mean abundances of magnoflorine jatrorrhizine, and oblongine were significantly (P < 0.05) higher in male plants while mean abundances of tetrahydropalmatine, norcoclaurine, and reticuline were significantly (P < 0.05) higher in female plants. CONCLUSIONS Phytochemicals in the stem of male and female Tinospora cordifolia showed significant qualitative and quantitative variations. LC-MS and MS/MS methods can be used to differentiate between male and female plants based on their chemical profiles and quantities of the marker bioactive alkaloids. This chemical composition difference was also evident during vegetative stage when there were no male and female flowers.

Rapid fingerprinting of Rauwolfia species using direct analysis in real time mass spectrometry combined with principal component analysis for their discrimination

Medicinal plants of the genus Rauwolfia (Apocynaceae) are extensively used as folk medicines worldwide. Its antihypertensive activity is well known due to the presence of monoterpene indole alkaloids (MIAs). The therapeutic potential of the herbal medicines are affected due to variation of bioactive phytoconstituents. Therefore, a rapid and validated method was developed for fingerprinting of roots and leaves of six Rauwolfia species by direct analysis in real time mass spectrometry (DART-MS). Seventeen bioactive MIAs were tentatively identified on the basis of their exact mass measurement from the intact plant parts. Furthermore, principal component analysis (PCA) was used to analyze the DART-MS data of six Rauwolfia species to identify the chemical markers. Thirteen and twenty-three chemical markers were identified from the roots and leaves which were able to discriminate among six Rauwolfia species. This method was also cross-validated for the rapid identification, authentication and quality control of Rauwolfia species.

A convenient synthesis of novel pyranosyl homo-C-nucleosides and their antidiabetic activities

A series of pyranosyl homo-C-nucleosides have been synthesized by reaction of butenonyl C-glycosides (5a-5j, and 8) and cyanoacetamide in presence of t-BuOK followed by further modifications. The reaction proceeds by Michael addition of cyanoacetamide to the butenonyl C-glycosides and subsequent dehydrative cyclization and oxidative aromatization to give glycosylmethyl pyridones (6a-6j, 7a-7j, 9, and 10). The glycosylmethyl pyridones (6a-6e) on reaction with POCl(3) under reflux gave respective glycosylmethyl pyridines (11a-11e and 12a-12e) in good yields. The synthesized compounds were screened for their in vitro α-glucosidase, glucose-6-phosphatase and glycogen phosphorylase inhibitory activities. One of the pyridylmethyl homo-C-nucleoside, compound 11d, displayed 52% inhibition of glucose-6-phosphatase as compared to the standard drug sodium orthovanadate while compound 12a showed a significant antihyperglycemic effect of 17.1% in the diabetic rats as compared to the standard drug metformin.