DIBAL-H-mediated N-deacetylation of tertiary amides: synthesis of synthetically valuable secondary amines.

A rapid DIBAL-H-mediated N-deacetylation of tertiary amides is described under mild conditions, affording synthetically valuable secondary amines in good to excellent yields.

N-Heterocyclic carbene-catalysed homoenolate addition reaction to 3-cyano-2-imino-2H-chromenes: synthesis of C4-functionalized 2-amino-3-cyano-4H-chromene.

A diastereoselective N-heterocyclic carbene-catalysed reaction between enal and 3-cyano-2-imino-2H-chromene is described for accessing a new type of C4-functionalized 2-amino-3-cyano-4H-chromene. A wide variety of enals and iminochromenes afforded the desired homoenolate addition product 2-amino-4H-chromenes in good yields and with moderate to good diastereoselectivities.

HFIP-promoted halo-carbocyclizations of N- and O-tethered arene-alkene substrates to access all halo (X = Br, I, Cl)-functionalized tetrahydroquinoline and chroman cores.

A new method for the stereoselective metal-, additive- and oxidant-free Friedel-Crafts-type halo-carbocyclization of N- and O-tethered arene-olefin substrates is reported, involving reaction with a suitable electrophilic halogenating reagent (NXS/DCDMH) in hexafluoroisopropanol. All halo (X = Br, I, Cl)-functionalized tetrahydroquinolines and chromans were obtained in excellent yields and with high levels of diastereocontrol (dr = >99 : 1), and these products were successfully transformed into synthetically useful compounds such as dihydroquinolines and partial or full azahelicene compounds.

Study on Chemotypic Variability of Coleus forskohlii Briq., Samples Collected from Different Phytogeographical Locations of India and Evaluation of Its Inhibitory Potential.

Coleus forskohlii Briq. is an important medicinal herb, endowed with a wide range of medicinal properties against the variety of ailments. Seven germplasm of C. forskohlii collected from different phyto-geographical locations and identification of elite chemotype was performed with the help of high performance thin layer chromatography. Data of soil analysis correlated with the bioactive compounds and inhibitory potential of the species. Quantification of forskolin and its isomer (iso-forskolin) content were done in all the collected samples of C. forskohlii, which revealed a wide range of variations, varying from 1.15-0.004% and 0.0091 to 0.1077% per dry weights basic, respectively. Variation in the bioactive content may be due to the soil nature and environmental factors. Soil analysis of collected samples demonstrated that there is significant variation in available NPK and micronutrient content and may be reasoned for existing chemotypic variability. In vitro biological activity (antioxidant and antidiabetic) analyses were performed, which reveals that germplasms have a high amount of forskolin and iso-forskolin, both show more activity. The aim of this study was to elucidate the effect of elicitors and precursors on the production of bioactive compounds and identification of best elite germplasm among the populations, to provide basic lead to the industry for commercial exploitability including its location-specific commercial cultivation.

Highly Selective and Catalytic C-N Bond Cleavage of Tertiary Sulfonamides: Scope and Mechanistic Insight.

A highly chemoselective C-N bond cleavage reaction of p-methoxybenzyl- (PMB), 3,4-dimethoxybenzyl- (DMB), or cinnamyl-substituted tertiary sulfonamides in the presence of catalytic Bi(OTf)3 is presented. A wide range of sulfonamide substrates smoothly furnished the corresponding C-N bond cleavage products in good to excellent yields. Great efforts have been made to obtain insights into the reaction mechanism based on a series of control experiments and mass spectroscopy.

Chemodiversity and molecular variability in the natural populations (India) of Gloriosa superba (L.) and correlation with eco- geographical factors for the identification of elite chemotype(s).

Gloriosa superba L. has economic significance due to colchicine, a bioactive compound used for gout. In present study metabolic and molecular variability in natural population of species was analyzed and correlated with edaphic and climatic factors. Thirty populations (wild) of G. superba were mapped from 10 different eco-regions of India at an elevation range of 10-1526 m, having no morphotypic variations. The two known biologically active alkaloids colchicine (ranged from 0.015-0.516%) and gloriosine (0.19-0.44%) were significantly varied (p < 0.05) among populations, leading to the identification of four elite chemotypes. Molecular variability from ISSR data divides the population in different sub clusters at intra-specific level, presenting the high similarity percentage with bootstrap value of 66-100%. Principal component analysis (PCA) revealed that elite chemotypes are related to temperature, precipitation and aridity gradient. The rhizospheric soil selenium was significantly correlated with colchicine content in G. superba.

Simultaneous Quantification of Pharmacologically Active Alkaloid Metabolites Colchicine and Gloriosine in Gloriosa Superba L. collected from Western Ghats (India) and Adjoining Areas for the Identification of Elite Chemotype(s).

BACKGROUND: Gloriosa superba is a valuable Ayurvedic medicinal plant and is in high demand in the world market for its colchicine content, which is used to treat gout. OBJECTIVE: The study aims (1) to record the metabolic variations in major bioactive metabolites, colchicine and gloriosine, in the natural populations of G. superba from Western Ghats and adjoining areas in India and (2) to develop HPTLC protocol for the identification of elite chemotypes of species and regulation of quality raw material, extract, and finished material. METHOD: Simultaneous quantification of colchicine and gloriosine in 22 natural populations through validated HPTLC as per ICH guidelines. RESULTS: Colchicine and gloriosine were identified at Rf 0.51 ± 0.03 and 0.41 ± 0.05 and the content varied from 0.021 to 0.86% and 0.003 to 0.198%. The method was found linear at a concentration range of 0.1-0.7 µg/spot, and LOD (3.3 σ/S) and LOQ (10 σ/S) was 0.71 and 2.16 µg/spot. The method was precise in the concentration range of 100-300 ng/spot, with 98.29% and 101.12% recovery (% RSD) for colchicine and gloriosine. Subsequently, four elite chemotypes were identified based on cluster analysis of metabolite content. CONCLUSION: The developed HPTLC method is linear, accurate, precise, and robust for simultaneous quantification of colchicine and gloriosine metabolite(s). Intraspecific metabolic variation was significant among the collected population, leading to the identification of four elite chemotypes. HIGHLIGHTS: Colchicine is an industrially viable metabolite and is therefore quintessential to the development of an economical and analytical method to regulate the quality of raw material, extract, and finished products.

Variability in alkaloid and phenolic content vis-a-vis antigout potential among the natural population of Gloriosa superba (L.) collected from Central India.

The variation in alkaloid metabolites (colchicine and gloriosine) was found significant in the nine germplasms of G. superba (L.), collected from Central India. The maximum content of colchicine and gloriosine was in NBG-15 (Chitrakoot, M.P) and NBG-13 (Bheraghat, M.P). The phenolic acids viz. quercetin and kaempferol was first ever quantified in G. superba tuber. Cluster analysis on chemical variability (colchicine and gloriosine content) results in the identification of three elite germplasm(s). The radical scavenging potential was also found promising in the selected elite germplasm viz. NBG-13, NBG-14 and NBG-15. Further, the protein denaturation potential of elite chemotypes was found at par with standard colchicine. The study will aid in site specific exploration of high metabolite yielding chemotype(s) with validated pharmacological action to meet out the industrial demands. This will also promotes the commercial cultivation of species for socio economical upliftment in the area having similar phyto geographical conditions.

Chemotaxonomic studies on natural population of Gloriosa superba (L.) collected from Gangetic plain (India) and their invitro antigout activity for the identification of elite germplasm(s).

ETHNOPHARMACOLOGICAL RELEVANCE: Gloriosa superba L. (Colchicaceae) is used in the treatment of gout and rheumatism as a traditional medicine dates back to 1810. It has also been used as ethnobotanical and folklore medicine to induce abortion/vaginal poison. AIM OF STUDY: The present study was carried out to identify the chemical variation existing in the major alkaloid metabolite (colchicine) in a threatened species, Gloriosa superba L. and is correlated with invitro antigout activity. MATERIAL AND METHOD: The samples (tuber) were collected from their natural locations in Gangetic plain of India. HPLC-PDA quantification of colchicine was done on C18 column at 245 nm and invitro antigout activity was analyzed by inhibition of protein denaturation, DPPH and Hydroxyl radical scavenging assay. RESULTS: The colchicine content within the 29 samples ranges from 0.021 to 0.665% and the maximum contents was in NBG-10 from Kanth (U.P). Such high colchicine (0.665%) containing natural population of G. superba is reported for the first time in Indian population. Four chemotypes viz. NBG-10, NBG-120, NBG-126 and NBG-88 were selected on the basis of colchicine content for invitro antigout activity. NBG-10 was separated from rest of the population exhibiting the most promising activity with high colchicine content. CONCLUSION: The outcomes will be helpful in the identification of elite chemotype for herbal product development and quality check of metabolites in raw material. The study will also support the site-specific commercial cultivation to meet out the industrial demand as well as income generation to farmers.

Using the Modified Clavien Grading System to Classify Complications of Percutaneous Nephrolithotomy.

PURPOSE: A modified Clavien classification system has been proposed to grade perioperative complications. We share our experience in grading the complications of percutaneous nephrolithotomy (PNL), according to this new classification. METHODS: A total of 809 PNLs performed between 2010 and 2014 were reviewed retrospectively. The modified Clavien classification system, which classifies the perioperative complications into 5 grades, was applied. Grade wise comparison of complications between the patients with simple and complex calculi was done. We also carried out a univariate analysis of different predictors of complications after surgery. RESULTS: A total of 253 perioperative complications were observed in 237 (29.29%) patients. Most complications were related to bleeding and urinary leakage. Patients with complex calculi had significantly more number of complications across all Clavien groups. In a univariate analysis, positive preoperative urine culture and multiple access for stone clearance were identified to be the independent predictors of complications. CONCLUSION: The modified Clavien system is a simplistic grading system for classification of postoperative complications. However, it suffers from various shortcomings. Therefore, till the proposition of a more comprehensive classification system, the modified Clavien system is useful for reporting the complications and short-term outcomes of PNL.

Simultaneous Quantification of Forskolin and Iso-Forskolin in Coleus forskohlii (Wild.) Briq. and Identification of Elite Chemotype, Collected from Eastern Ghats (India).

BACKGROUND: Coleus forskohlii is a well-known industrially important medicinal plant, for its high forskolin content. OBJECTIVE: A simple, selective, and sensitive high-performance thin layer chromatography (HPTLC) method was developed and validated for simultaneous quantification of forskolin and iso-forskolin in C. forskohlii germplasm collected from the Eastern Ghats, India. MATERIALS AND METHODS: Chromatographic separation of the targeted marker(s) was obtained on precoated silica plates using toluene: ethyl acetate: methanol (90:30:0.5, v/v/v) as the mobile phase. RESULTS: Densitometric quantification of forskolin and iso-forskolin was carried out at 545 nm. Forskolin and iso-forskolin were identified by comparing the ultraviolet spectra of standard and sample track at Rf of 0.64 ± 0.02 and 0.36 ± 0.01, after derivatization with anisaldehyde sulfuric acid reagent. The linearity of both the analytes was obtained in the range of 300-1200 ng/spot with the regression coefficient (R2) of 0.991 and 0.986. Recovery of analyte (s) at three levels, namely, 100, 150, and 200 ng/spot was found to be 100.46% ± 0.29%, 99.64% ± 0.33%, 100.02% ± 0.76% and 99.76% ± 0.62%, 99.56% ± 0.35%, 100.02% ± 0.22%, respectively, for forskolin and iso-forskolin. The content of forskolin and iso-forskolin varies from 0.046% to 0.187% and 0.002% to 0.077%, respectively (dry weight basis), the maximum content of both the markers was found in NBC-31, from Thakurwada, Maharashtra. CONCLUSION: The developed HPTLC method was linear, accurate, and reliable as per the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The study aids in the identification of elite chemotype for commercial prospection of industrially viable medicinal crop. SUMMARY: 12 Samples are collected from different locations of the eastern ghat regionsQuantification of two major marker forskolin and iso forskolinThe maximum content of both the markers was found in NBC -31, from Thakurwada, MaharashtraIdentification of elite chemotype of collected samples may be useful for commercial prospection in industries.

High-performance Thin-layer Chromatographic-densitometric Quantification and Recovery of Bioactive Compounds for Identification of Elite Chemotypes of Gloriosa superba L. Collected from Sikkim Himalayas (India).

BACKGROUND: Gloriosa superba L. (Colchicaceae) is used as adjuvant therapy in gout for its potential antimitotic activity due to high colchicine(s) alkaloids. OBJECTIVE: This study aimed to develop an easy, cheap, precise, and accurate high-performance thin-layer chromatographic (HPTLC) validated method for simultaneous quantification of bioactive alkaloids (colchicine and gloriosine) in G. superba L. and to identify its elite chemotype(s) from Sikkim Himalayas (India). METHODS: The HPTLC chromatographic method was developed using mobile phase of chloroform: acetone: diethyl amine (5:4:1) at λmax of 350 nm. RESULTS: Five germplasms were collected from targeted region, and on morpho-anatomical inspection, no significant variation was observed among them. Quantification data reveal that content of colchicine (Rf: 0.72) and gloriosine (Rf: 0.61) varies from 0.035%-0.150% to 0.006%-0.032% (dry wt. basis). Linearity of method was obtained in the concentration range of 100-400 ng/spot of marker(s), exhibiting regression coefficient of 0.9987 (colchicine) and 0.9983 (gloriosine) with optimum recovery of 97.79 ± 3.86 and 100.023% ± 0.01%, respectively. Limit of detection and limit of quantification were analyzed, respectively, as 6.245, 18.926 and 8.024, 24.316 (ng). Two germplasms, namely NBG-27 and NBG-26, were found to be elite chemotype of both the markers. CONCLUSION: The developed method is validated in terms of accuracy, recovery, and precision studies as per the ICH guidelines (2005) and can be adopted for the simultaneous quantification of colchicine and gloriosine in phytopharmaceuticals. In addition, this study is relevant to explore the chemotypic variability in metabolite content for commercial and medicinal purposes. SUMMARY: An easy, cheap, precise, and accurate high performance thin layer chromatographic (HPTLC) validated method for simultaneous quantification of bioactive alkaloids (colchicine and gloriosine) in G. superba L.Five germplasms were collected from targeted region, and on morpho anatomical inspection, no significant variation was observed among themQuantification data reveal that content of colchicine (Rf: 0.72) and gloriosine (Rf: 0.61) varies from 0.035%-0.150% to 0.006%-0.032% (dry wt. basis)Two germplasms, namely NBG 27 and NBG 26, were found to be elite chemotype of both the markers.

Fe(OTf)3-catalysed Friedel-Crafts reaction of benzenoid arenes with α,ß-unsaturated carbonyl compounds: easy access to 1,1-diarylalkanes.

A simple and efficient method for the synthesis of 1,1-diarylalkanes via the Friedel-Crafts-type alkylation reaction of electron-rich arenes with cinnamic acid ester derivatives or chalcones is reported. Iron triflate has been found to be the best catalyst for the Friedel-Crafts-type alkylation reaction with α,ß-unsaturated carbonyl compounds. This reaction afforded ß,ß-diaryl carbonyl compounds in good yields (65-93%) and with excellent regioselectivities. Remarkably, this method is also compatible with a variety of indoles to provide 3-indolyl-aryl carbonyl compounds in excellent yields. Great efforts have been made to deduce a plausible reaction mechanism based on isotopic labelling experiments.

Reversed Phase High-Performance Liquid Chromatographic Ultra-violet (Photo Diode Array) Quantification of Oleanolic Acid and its Isomer Ursolic Acid for Phytochemical Comparison and Pharmacological Evaluation of Four Leucas Species Used in Ayurveda.

CONTENT: Different Leucas species are well known as "Dronpushpi," a well-known herb of Ayurveda, used in the treatment of various ailments. OBJECTIVE: Evaluation of four industrially important Leucas species for their in vitro antidiabetic potential and radical scavenging effect along with high-performance liquid chromatographic quantification of the bioactive triterpenes. MATERIALS AND METHODS: The quantification of triterpenes was carried out on C-18 column with acetonitrile and water (90:10) as the solvent system at a detection wavelength of 210 nm. In vitro antidiabetic activity was evaluated by α-amylase inhibition assay based on starch-iodine and 3,5 dinitrosalicylic acid (DNS) method. Antioxidant activity was calculated by five different models, namely total phenolic and total flavonoid content, free radical scavenging activity by 1-1-diphenyl-2-pic-rylhydrazyl (DPPH), ferric-reducing power assay, and the total antioxidant capacity. RESULTS: Maximum concentration of oleanolic acid was found in Leucas cristata, followed by Leucas mollissima, Leucas Aspera, and Leucas biflora. Ursolic acid was highest in L. mollissima and then in L. biflora, L. cristata, and L. aspera, respectively. In in vitro antidiabetic activity, IC50 of L. aspera (1.56 ± 0.01 mg/ml) and L. mollissima (0.75 ± 0.005 mg/ml) were found to be highest in DNS and iodine starch assay. IC50 in DPPH assay ranges from 0.6 ± 0.011 to 1.68 ± 0.011 mg/ml. Antioxidant capacity follows the order; L. aspera > L. mollissima > L. biflora > L. cristata. CONCLUSION: Promising activities were observed in targeted species, thus L. mollissima, L. biflora, and L. cristata can be used alternatively as a substitute to L. aspera. SUMMARY: Physicochemical parameters are within the limit as per the Ayurvedic Pharmacopoeia of IndiaMaximum concentration of oleanolic acid was found in Leucas cristata; however, ursolic acid was highest in Leucas mollissima In vitro antidiabetic activity of Leucas aspera and L. mollissima was found to be heighest as compared to other species. However, antioxidant capacity is almost similar in targeted species.Promising activities were observed in all the species, thus L. mollissima, Leucas biflora, and L. cristata can be used alternatively as a substitute to L. aspera.

Penile incarceration with encircling metallic objects: a study of successful removal.

OBJECTIVE: This article aimed to study the various treatment options according to the grading scale for penile incarceration. MATERIALS AND METHODS: A retrospective review, of all the case files of patients presented with penile incarceration with encircling metallic object was performed. The patients were analyzed for age, marital status, motive, object used, who applied it, trauma grade, duration of incarceration, removal technique, removal time, anesthesia used and recovery time. RESULT: A total of seven patients were identified. The average age was 46.71 years. Self-sexual gratification was the most common motive (five patients). Six patients presented within 24 hours. Grade II of injury was commonest type of injury seen in five patients.The technique of removal chosen was according to grade of penile injury, duration of incarceration and type of object used. Spinal anesthesia was used in most of the cases (five patients). CONCLUSION: Penile incarceration with encircling metallic objects is a rare presentation and requires urgent intervention according to trauma grade to prevent complications.