Publications
Balaji M Ghodake, Sayantan Paul and Asish K Bhattacharya*
ChemistrySelect 9 (36), e202403280
In this review, essentially transition-metal-free conditions for C−C bond formation reactions in indoles has been explored. This review describes various approaches of functionalization at the C-2, C-3, C-4 and C-7 position of indoles which comprises arylation, alkenylation, acylation, formylation, alkylation, bisindolyl and cyclization strategies. Also, strategies incorporating N-alkylation/arylation has also been covered.
A Short Review on the Synthetic Routes for the Antiepileptic Drug (S)‑Levetiracetam
Sayantan Paul and Asish K Bhattacharya*
Org. Process Res. Dev. 2024, 28, 4, 924–936
Epilepsy is a chronic disorder characterized by recurrent unpredictable seizures. Levetiracetam (Keppra) wasintroduced by UCB for the treatment of partial onset seizures in patients above 16 years of age diagnosed with epilepsy. This reviewreports synthetic strategies available for the synthesis of (S)-levetiracetam and will certainly aid the quest for the development of newroutes for its synthesis.
1,6-Conjugate addition of in situ generated aryldiazenes to
p-quinone methides
Ajay G. Mamale, Sayantan Paul, Rajesh G. Gonnade and Asish K. Bhattacharya*
Org. Biomol. Chem., 2024,22, 5636-5645
Herein we report a transition-metal free, base-mediated 1,6-conjugate addition of aryldiazenes to paraquinone methides (p-QMs). Arylhydrazines were used for the in situ generation of aryldiazenes using a base-mediated protocol in the presence of air as the oxidant. The 1,6-conjugate addition of aryldiazenes to para-quinone methides via a radical mechanism is followed by an oxidative rearrangement to furnish the desired product, arylhydrazones. Interestingly, our synthetic protocol results in the formation of an aryldiazene radical, which undergoes 1,6-conjugate addition with p-QMs to furnish the arylhydrazones
Methanesulfonic Acid-Catalyzed Friedel-Crafts Alkylation: Towards Sustainable Synthesis of Arylalkanes from Donor–Acceptor Cyclopropane Ketones
Lakshmi Goswami, Sayantan Paul, Ajay G. Mamale, Dr. Rajesh G. Gonnade
and Asish K. Bhattacharya*
Asian J. Org. Chem. 2024, 13, e202400116
We present herein Brønsted acid-catalyzed Friedel-Crafts alkylation of phenols with Donor–Acceptor cyclopropane ketones. The presence of the 1,4-diphenyl butan-1-one and 1,3-diphenyl propane-1-one motifs in various naturally occurring biologically significant molecules inspired us to pursue the direct synthesis of these structural frameworks. Utilizing methanesulfonic acid (MeSO3H) as a catalyst, we achieved a more environmentally friendly and high-yielding synthesis, owing to its cost-effectiveness, biodegradability, transition–metal and additives free conditions. Furthermore, we have successfully extended our developed methodology to thiophenols, resulting in the production of sulfur–based butan-1-one derivatives in good yields.
Lovely Gupta, Shalini Verma, Lakshmi Goswami, Himanshu Kamboj, Pooja Sen,
Asish K Bhattacharya* and Pooja Vijayaraghavan*
Journal of Applied Microbiology, 2024, 135, 1–14
This study’s significance lies in uncovering the antifungal mechanisms and safety profile of compound 6i against Aspergillus fumigatus, offering insights into cell wall integrity, gene expression, and potential therapeutic applications, thereby contributing to the advancement of antifungal research.
Design and Synthesis of 1,3-Diynes as Potent Antifungal Agents against Aspergillus fumigatus
1,3-Diynes were synthesized via Glaser-Hay and Cadiot-Chodkiewicz coupling reactions to furnish potent antifungal agents. All compounds were evaluated against the pathogenic fungus, A. fumigatus, and one compound in particular was found to exhibit promising antifungal activity, suggesting this type of scaffold to be suitable for developing new antifungal agents. The most active compound also exhibited significant anti-biofilm activity.Part of a joint special collection highlighting research from CSIR Institutes.
Late-Stage C(sp2)−H Arylation of Artemisinic Acid and Arteannuin B: Effect of Olefin Migration Towards Synthesis of
C-13 Arylated Artemisinin Derivatives
Sayantan Paul, Balaji M. Ghodake and Asish K. Bhattacharya*
Chemistry–An Asian Journal 18 (8), e202300162
In recent years, C−H bond functionalization has emerged as a pivotal tool for late‐stage functionalization of complex natural products for the synthesis of potent biologically active derivatives. Artemisinin and its C‐12 functionalized semi‐synthetic derivatives are well‐known clinically used anti‐malarial drugs due to the presence of the essential 1,2,4‐trioxane pharmacophore. However, in the wake of parasite developing resistance against artemisinin‐based drugs, we conceptualized the synthesis of C‐13 functionalized artemisinin derivatives as new antimalarials. In this regard, we envisaged that artemisinic acid could be a suitable precursor for the synthesis of C‐13 functionalized artemisinin derivatives. Herein, we report C‐13 arylation of artemisinic acid, a sesquiterpene acid and our attempts towards synthesis of C‐13 arylated artemisinin derivatives. However, all our efforts resulted in the formation of a novel …
An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies
Tharun K Kotammagari, Sweta Misra, Sayantan Paul, Sunita Kunte, Rajesh G Gonnade, Manas K Santra and Asish K Bhattacharya*
Beilstein J. Org. Chem. 2023, 19, 204–211
The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut-Currier (RC) dimerization. The other key steps of the synthesis are oxaMichael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the configuration of each enantiomer was determined by single-crystal Xray analysis. In addition, one-pot synthesis of (±)-incarviditone has been achieved from racrengyolone by using KHMDS as a base. We have also assessed the anti-cancer activity of all the synthesized compounds in breast cancer cells nonetheless, they exhibited very limited growth suppression activity.
Lovely Gupta, Pooja Sen, Asish K Bhattacharya* and Pooja Vijayaraghavan*
Archives of Microbiology (2022) 204:214
Aspergillus fumigatus is one of the major pathogenic fungal species, causing life-threatening infections. Due to a limited spectrum of available antifungals, exploration of new drug targets as well as potential antifungal molecules has become pertinent. Rodlet layer plays an important role in adherence of fungal conidia to hydrophobic cell surfaces in host, which also leads to A. fumigatus biofilm formation, contributing factor to fungal pathogenicity. From decades, natural sources have been known for the development of new active molecules. The present study investigates effect of isoeugenol on genes responsible for hydrophobins (RodA), adhesion as well as biofilm formation (MedA and SomA) of A. fumigatus. Minimum inhibitory concentrations (MIC and IC50) of isoeugenol against A. fumigatus were determined using broth microdilution assay. The IC50 results showed reduced hydrophobicity and biofilm formation …
Glycal mediated synthesis of piperidine alkaloids: fagomine, 4-epi-fagomine, 2-deoxynojirimycin, and an advanced intermediate, iminoglycal
Hemender R. Chand, Mritunjay K. Tiwari and Asish K. Bhattacharya*
RSC Adv., 2022, 12, 33021-33031
Glucal and galactal are transformed into 2-deoxyglycolactams, which are important building blocks in the synthesis of biologically active piperidine alkaloids, fagomine and 4-epi-fagomine. In one of the strategies, reduction of 2-deoxyglycolactam-N-Boc carbonyl by lithium triethylborohydride (Super-Hydride®) has been exploited to generate lactamol whereas reduction followed by dehydration was utilized as the other strategy to functionalize the C1–C2 bond in the iminosugar substrate. The strategies provide the formal synthesis of 2-deoxynojirimycin, nojirimycin and nojirimycin B......
Design and synthesis of eugenol/isoeugenol glycoconjugates and other analogues as antifungal agents against Aspergillus fumigatus
Lakshmi Goswami, Lovely Gupta, Sayantan Paul, Maansi Vermani, Pooja Vijayaraghavan and Asish K. Bhattacharya*
RSC Med. Chem., 2022, 13, 955-962
Glycoconjugates are biologically significant molecules as they tend to serve a wide range of intra- and extra-cellular processes depending on their size and complexity. The secondary metabolites of the plant Myristica fragrans, eugenol and isoeugenol, have shown antifungal activities (IC50 1900 μM). Therefore, we envisioned that glycoconjugates based on these two scaffolds could prove to be potent antifungal agents. Triazole-containing compounds have shown prominent activities as antifungal agents. Based on this, we opined that a Cu(I) catalyzed click reaction could serve as the bridging tool between a eugenol/isoeugenol moiety and sugars to synthesize eugenol/isoeugenol based glycoconjugates. In our present work, we have coupled propargylated eugenol/isoeugenol and azido sugar to furnish eugenol/isoeugenol based glycoconjugates. In another approach, we have carried out hydroxylation of the …
Combating multi-drug resistant malaria parasite by inhibiting falcipain-2 and heme-polymerization: Artemisinin-peptidyl vinyl phosphonate hybrid molecules as new antimalarials
Eswar K. Aratikatla, Md Kalamuddin, Kalpeshkumar C. Rana, Gaurav Datta, Mohd Asad, Srividhya Sundararaman, Pawan Malhotra, Asif Mohmmed and Asish K. Bhattacharya*
European Journal of Medicinal Chemistry 220 (2021) 113454
Artemisinin-based combination therapies (ACTs) have been able to reduce the clinical and pathological malaria cases in endemic areas around the globe. However, recent reports have shown a progressive decline in malaria parasite clearance in South-east Asia after ACT treatment, thus envisaging a need for new artemisinin (ART) derivatives and combinations. To address the emergence of drug resistance to current antimalarials, here we report the synthesis of artemisinin-peptidyl vinyl phosphonate hybrid molecules that show superior efficacy than artemisinin alone against chloroquine-resistant as well as multidrug-resistant Plasmodium falciparum strains with EC50 in pico-molar ranges. Further, the compounds effectively inhibited the survival of ring-stage parasite for laboratory-adapted artemisinin-resistant parasite lines as compared to artemisinin. These hybrid molecules showed complete parasite …
Eswar K. Aratikatla, Md Kalamuddin, Pawan Malhotra, Asif Mohmmed
and Asish K. Bhattacharya*
ACS Omega 2020, 5, 45, 29025–29037
Racemic and enantioselective syntheses of γ-phenyl-γ-amino vinyl phosphonates and sulfones have been achievedusing Horner−Wadsworth−Emmons olefination of trityl protected α-phenyl-α-amino aldehydes with tetraethyl methylenedi-phosphonate and diethyl ((phenylsulfonyl)methyl)phosphonate, respectively, without any racemization. The present strategy hasalso been successfully applied to the synthesis of peptidyl vinyl phosphonate and peptidyl vinyl sulfone derivatives as potentialcysteine protease inhibitors of Chagas disease, K11002, with 100% de. The developed synthetic protocol was further utilized tosynthesize hybrid molecules consisting of artemisinin as an inhibitor of major cysteine protease falcipain-2 present in the foodvacuole of the malarial parasite. The synthesized artemisinin−dipeptidyl vinyl sulfone hybrid compounds showed effective in vitroinhibition of falcipain-2 and potent parasiticidal efficacies against Plasmodium falciparum in nanomolar ranges. Overall, the developedsynthetic protocol could be effectively utilized to design cysteine protease inhibitors not only as novel antimalarial compounds butalso to be involved in other life-threatening diseases
Synthesis of artemisinic acid derived glycoconjugates
and their anticancer studies
Tharun K. Kotammagari, Sayantan Paul, Ganesh K. Barik, Manas K. Santra
and Asish K. Bhattacharya*
Org. Biomol. Chem., 2020, 18, 2252-2263
Glycoconjugates, due to their diverse functions, are widely regarded as biologically important molecules. Artemisinic acid 1 occurs naturally in the plant Artemisia annua and is considered to be the biogenetic precursor of the antimalarial drug, artemisinin 2. We report herein the design and synthesis of diverse artemisinic acid derived glycoconjugates. We have synthesized 12-O-artemisinic acid-glycoconjugates (7a–k) and 12-N-artemisinic acid-glycoconjugates (8a–k) by utilizing Cu(I)-catalyzed azide-alkyne cycloaddition reactions (Click chemistry) with various synthesized sugar azides (6a–k) in good to excellent yields along with two fluorescently labeled compounds, 12-O-artemisinic acid-glycoconjugate 11 and 12-N-artemisinic acid-glycoconjugate 12, to investigate the mode of action of these compounds in biological systems. All the synthesized artemisinic acid glycoconjugates were assayed for their efficacy against the MCF7 cell line. Our anticancer studies indicated that all the synthesized compounds inhibited the growth of MCF7 cells in a dose dependent manner, barring compounds 4 and 7d. However, these compounds exhibit moderate cytotoxicity, as is evident from their IC50 values.
A Short Review of Synthetic Routes for the Antiepileptic
Drug (R)-Lacosamide
Eswar K. Aratikatla and Asish K. Bhattacharya*
Org. Process Res. Dev. 2020, 24, 1, 17–24
The disease epilepsy affects people of all ages and is due to a chronic neurological disorder in the brain. According to a report by the World Health Organization, epilepsy is one of the most common global neurological diseases. (R)-Lacosamide (Vimpat) was introduced by UCB Pharma in 2008 for the treatment of partial-onset seizures in patients suffering from epilepsy. This review summarizes all of the available synthetic strategies reported for (R)-lacosamide, which will help medicinal chemists in the further development of its synthesis.
Unusual Epimerization in Styryllactones: Synthesis of (−)-5-Hydroxygoniothalamin, (−)-5-Acetylgoniothalamin,
and O-TBS-Goniopypyrone
Tharun K. Kotammagari, Sayantan Paul and Asish K. Bhattacharya*
ACS Omega 2019, 4, 27, 22549–22556
(−)-5-Hydroxygoniothalamin, (−)-5-acetylgoniothalamin, and (+)-5-hydroxygoniothalamin, isolated from the Goniothalamus genus, are synthesized from triacetyl-O-d-glucal by employing the Ferrier reaction, Mitsunobu reaction, and Jones oxidation as key steps. The synthetic procedure also yields the epimers of (−)-5-hydroxygoniothalamin and (+)-5-hydroxygoniothalamin employing acid-mediated transition-metal-free epimerization at C-5 of styryllactones. Further studies reveal that the epimerization is facilitated by the phenyl group present on the styryllactones. Also, depending on the dihydroxylation reaction conditions, various analogues of saturated styryllactones are synthesized utilizing oxa-Michael reaction conditions.
The reactions of 2-lithiothiazole on 3,4,6-tri-O-benzyl-2-deoxyglyconolactones have been studied, which resulted in the formation of two products, major (3,4,6-tri-O-benzyl-2-deoxy-1-(2-thiazolyl) glycal) and minor products 3,4,6-tri-O-benzyl-2-deoxy-1-(2-thiazolyl) glycal hemiketal. The hemiketal-keto tautomerism in solution was observed in the minor product. The tautomerism has been studied in various organic solvents and their ratios have been determined by 1H NMR spectroscopy. The major product from the reaction of 2-lithiothiazole with 2-deoxygluconolactone was utilized for the synthesis of 3-deoxy-D-arabino-2-heptulosonic acid DAH 4 a and 3-deoxy-D-arabino-2-heptulopyranose commonly known natural product kamusol 6 a via acid catalyzed hydration followed by stereoselective methyl glycoside bond formation. Similarly, major product from 2-deoxygalactonolactone furnished 5-epi-DAH 4 b (C-5 epimer of 4 a) and 5-epi-kamusol 6 b (C-5 epimer of 6 a). The minor product has also been utilized for the synthesis of DAH 4 a, 5-epi-DAH 4 b, kamusol 6 a and 5-epi-kamusol 6 b through a common intermediate, α-methyl glycosylated product.
Synthesis of artemisinin derived glycoconjugates
inspired by click chemistry
Lakshmi Goswami, Sayantan Paul, Tharun K. Kotammagari and Asish K. Bhattacharya*
New J. Chem., 2019, 43, 4017-4021
Herein we describe the synthesis of artemisinin based glycoconjugates (9a–i) through employing a Cu(I)-catalysed reaction between β-propargylated dihydroartemisinin (7a) and azido sugars (8a–i), with moderate to excellent yields. Our synthesized artemisinin based glycoconjugates (9a–i) could prove to be an interesting class of bioactive molecules, suitable for the study of their various biological activities.
Synthesis and anticancer studies of Michael adducts and Heck arylation products of sesquiterpene lactones, zaluzanin D and zaluzanin C from Vernonia arborea
Tushar R. Valkute, Eswar K. Aratikatla, Neha A. Gupta, S. Ganga,
Manas K. Santra and Asish K. Bhattacharya*
RSC Adv., 2018, 8, 38289–38304
Sesquiterpene lactones containing α-methylene-γ-lactones, zaluzanin D 1 and zaluzanin C 2 were isolated from the leaves of Vernonia arborea. Several diverse Michael adducts (3–22) and Heck arylation analogs (23–34) of 1 have been synthesized by reacting with various amines and aryl iodides, respectively and were assayed for their in vitro anticancer activities against human breast cancer cell lines MCF7 and MDA-MB-231. Among all the synthesized analogs, Michael adducts 9 and 10 showed better anticancer activities as compared to 1. However, among these compounds, only 10 has minimal cytotoxic effect on normal breast epithelial MCF10A cells. Our detailed mechanistic studies reveal that compounds 9 and 10 execute their antiproliferative activity through induction of apoptosis and thereby inhibit the cancer cells proliferation and compound 10 could be a lead compound for designing potential anti-cancer compound.
Hydroxyl directed C-arylation: synthesis of 3-hydroxyflavones and
2-phenyl-3-hydroxy pyran4-ones under transition-metal free conditions
Sayantan Paul and Asish K. Bhattacharya*
Org. Biomol. Chem., 2018, 16, 444–451
An efficient, transition-metal free and direct C-arylation of 3-hydroxychromone moieties in the presence of a base, air as an oxidant and arylhydrazines as arylating agents to furnish highly biologically active flavonols or 3-hydroxyflavones has been developed. We have further extended our methodology for the C-arylation of the 5-hydroxy pyran-4-one moiety. The role of the free hydroxyl group towards C-arylation has been delineated.
Eswar K Aratikatla, Tushar R Valkute, Sunil K Puri, Kumkum Srivastava and Asish K Bhattacharya*
European Journal of Medicinal Chemistry 138 (2017) 1089-1105
Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further …
Biomimetic Total Synthesis of Angiopterlactone B and Other Potential Natural Products
Tharun K. Kotammagari, Rajesh G. Gonnade and Asish K. Bhattacharya*
Org. Lett. 2017, 19, 13, 3564–3567
A one-pot biomimetic synthesis of (−)-angiopterlactone B and its enantiomer (+)-angiopterlactone B has been accomplished via TBAF-catalyzed tandem ring contraction followed by oxa-Michael/Michael addition sequence. Comparison of specific optical rotations, absolute configurations, and CD spectra of natural, synthesized (−)-angiopterlactone B and (+)-angiopterlactone B unequivocally proves that the isolated angiopterlactone B must be levorotatory. Synthesis of hitherto undiscovered natural products 18 and 20 and analogues of angiopterlactone B demonstrate the versatility of this method.
Efficient synthesis of functionalized olefins by Wittig reaction using Amberlite resin as a mild base
Tushar R. Valkute, Eswar K. Aratikatla and Asish K. Bhattacharya*
SYNTHETIC COMMUNICATIONS 2017, 6, 581–589
A convenient procedure for the synthesis of olefins by the reaction ofstabilized, semistabilized, and nonstabilized phosphorous ylides withvarious aldehydes or ketone using Amberlite resin as a mild base isdescribed. Our developed method offers facile and racemization-freesynthesis of α,β-unsaturated amino esters and chiral allylic amine. Thedeveloped methodology offers mild reaction conditions, high effi-ciency, and facile isolation of the final products, a practical alternativeto known procedures.
Naturally Occurring Anti-TB Agents: Isolation, Chemical Transformations and In Vitro Antitubercular Activities of Secondary Metabolites of Rhizomes of Alpinia galanga
Tushar R. Valkute , Manisha Arkile , Dhiman Sarkar and Asish K. Bhattacharya*
Planta Medica International Open 2016; 3(03): e55-e59
A bioactivity-guided chemical examination of the acetone extract of the rhizomes of Alpinia galanga led to the isolation of six secondary metabolites, eucalyptol derivative (1) and phenylpropanoids (2–6). The structures of all of the isolated compounds (1–6) were elucidated on the basis of their spectral data. The isolated compounds (1–6) were in vitro assayed against active and dormant phenotypes of Mycobacterium tuberculosis H37Ra, respectively. Interestingly, 1′S-1′-acetoxychavicol acetate (2) showed good antitubercular activities against both active and dormant phenotypes of M. tuberculosis with IC50 values of 1.04 µM and 2.69 µM, respectively. Tsuji-Trost and homodimerization reactions of the active compound (2) respectively resulted in the formation of two analogues, 7 and 8. Both of these synthesized analogues were also found to be active in vitro against active [IC50 s of 3.24 and 3.87 µM, respectively, for compounds 7 and 8] and dormant [IC50 s of 8.33 and 2.41 µM, respectively, for compounds 7 and 8] phenotypes of M. tuberculosis H37Ra, respectively.
Diastereoselective Synthesis of β-Ether Derivatives of Artemisinin, an Antimalarial Drug: The Effect of Nitrile on Stereoselectivity
Hemender R. Chand and Asish K. Bhattacharya*
Asian J. Org. Chem. 2016, 5, 201 – 206 (Cover Page Article)
Malaria is a life-threatening disease affecting a major portion of the world's population with considerable loss of human life. Artemisinin, isolated from Artemisia annua, its oil- and water-soluble derivatives, and other known antimalarials are recommended for artemisinin combination therapy by the World Health Organization. We have established a method for the stereoselective synthesis of β-ether derivatives of dihydroartemisinin in high yield and high diastereoselectivity. The reaction either in acetonitrile or dichloromethane/trichloroacetonitrile (6:1) mixtures at 0 °C or room temperature, respectively, furnished the antimalarial drugs artemether 3 or arteether 4 in high yield with a high diastereomeric ratio. The effect the nitrile has on the yield and stereoselectivity is mechanistically explained.
Synthesis of naturally occurring (+)-osmundalactone and
4-epi-(+)-osmundalactone from triacetyl-O-D-glucal
Tharun K. Kotammagari, Rajesh G. Gonnade and Asish K. Bhattacharya*
Tetrahedron Letters 56 (2015) 2783–2786
An efficient total synthesis of (+)-osmundalactone 1 has been achieved starting from readily available triacetyl-O-D-glucal 6 employing Ferrier rearrangement and Jones oxidation as key steps. Also, synthesis of 4-epi-(+)-osmundalactone 2 was accomplished from the common key intermediate 9. The absolute stereochemistry of (+)-osmundalactone 1 and a precursor of 4-epi-(+)-osmundalactone 2 have been established by single crystal X-ray analysis. The overall yield of compound 1 and 2 from triacetyl-O-Dglucal 6 is 13% and 8%, respectively.
Direct Glycosylation of Unprotected and Unactivated Sugars Using Bismuth Nitrate Pentahydrate
Innaiah K. Polanki, Siva H. Kurma and Asish K. Bhattacharya*
Journal of Carbohydrate Chemistry, 34:196–205, 2015
Bi(NO3)3 , a low-cost, mild, and environmentally green catalyst, has been successfully utilized for Fischer glycosylation for the synthesis of alkyl/aryl glucopyranosides by re-acting unprotected sugars, namely, D-glucose, L-rhamnose, D-galactose, D-arabinose, and N-acetyl-D-glucosamine with various alcohols in good to excellent yields. The glycosides were formed with high α-selectivity. Further, an expedient separation of α- and β-glycosides using silver nitrate–impregnated silica gel flash liquid chromatography has been developed.
Clerodane type diterpene as a novel antifungal agent from Polyalthia longifolia var. pendula
Asish K. Bhattacharya*, Hemender R. Chand, Jyothis John and Mukund V. Deshpande
European Journal of Medicinal Chemistry 94 (2015) 1-7
Bioactivity-guided chemical examination of methanolic extract of leaves of Polyalthia longifolia var. pendula led to the isolation of the active constituent, a diterpene 1 which was identified as 16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide on the basis of its spectral data. Among the tested strains, diterpene 1 was found to exhibit antifungal activities having MIC90 values of 50.3, 100.6 and 201.2 μM against Candida albicans NCIM3557, Cryptococcus neoformans NCIM3542 (human pathogens) and Neurospora crassa NCIM870 (saprophyte), respectively. Initial, structure–activity-relationship (SAR) data generated by synthesizing some derivatives revealed that the double bond between C3–C4 and the free hydroxyl group at C16 are crucial for the antifungal activity of the diterpene 1. The mode of action of 1 in C. albicans is due to compromised cell membrane permeability and also probably due to disruption of cell …
Efficient Bakers’ Yeast-Catalyzed Multicomponent Synthesis of α-Aminophosphonates in One Pot
Asish K. Bhattacharya* and Mohammad Mujahid
Synthetic Communications, 2013, 43, 2583–2589
Utilizing bakers’ yeast (Saccharomyces cerevisiae) as a biocatalyst, synthesis of a-aminophosphonates in one pot has been accomplished by the three-component reaction ofan aldehyde, an amine, and diethyl phosphite in moderate to good yields under solvent-free reaction conditions.
Diversity-oriented synthesis of a-aminophosphonates: A new class of potential anticancer agents
Asish K. Bhattacharya,* Dnyaneshwar S. Raut, Kalpeshkumar C. Rana, Innaiah K. Polanki, Mohd Sajid Khan and Sana Iram
European Journal of Medicinal Chemistry 66 (2013) 146-152
A small library of structurally diverse a-aminophosphonates has been synthesized by reacting alkyl/aryl aldehydes, alkyl/aryl amines and alkyl/aryl phosphites in one-pot catalyzed by Amberlite-IR 120 resin (acidic). All the synthesized a-aminophosphonates were assayed for their in vitro cytotoxic activities against a panel of five human cancer cell lines including A-549, NCI-H23 (Lung), Colo 320DM (Colon), MG-63 (Bone marrow) and Jurkat (Blood T lymphocytes). Compound 4n having (R)-1-phenylethanamine was found to be the most active amongst all the synthesized a-aminophosphonates against all the five cancer cell lines, most prominent being against Jurkat cell line with an IC50 value of 4 mM. Surprisingly, compound 4o having (S)-1-phenylethanamine was found to be devoid of any cytotoxicity. Our finding suggests that these chemical entities could further serve as interesting template for the design of potential anticancer agents.
An Efficient Synthesis of a Hydroxyethylamine (HEA) Isostere and Its α-Aminophosphonate and Phosphoramidate Derivatives as Potential Anti-HIV Agents
Asish K. Bhattacharya,* Kalpeshkumar C. Rana, Christophe Pannecouque and Eric De Clercq
ChemMedChem 2012, 7(9), 1601-1611
Efficient synthesis of a hydroxyethylamine (HEA) isostere was carried out with a one-pot reduction–transimination–reduction reaction sequence. α-Aminophosphonate and phosphoramidate derivatives of the HEA isostere were designed and synthesized. All of the synthesized α-aminophosphonate and phosphoramidate derivatives were assayed for their anti-HIV activities.
Design, synthesis and biological evaluation of peptidyl-vinylaminophosphonates as novel cysteine protease inhibitors
Asish K. Bhattacharya* and Kalpeshkumar C. Rana
Bioorg. Med. Chem. 19 (2011) 7129–7135
We report herein, design and synthesis of vinylaminophosphonates, a novel class of compounds as possible cysteine protease inhibitors. The synthesis of vinylaminophosphonates has been accomplished employing Tsuji–Trost reaction as a key step. The synthesized compounds were assayed against papain, a model cysteine protease and some of our synthesized compounds showed IC50 values in the range of 30–54 lM thereby suggesting that these chemical entities thus could constitute an interesting template for the design of potential novel protease inhibitors.
Asish K. Bhattacharya,* Kalpeshkumar C. Rana, Dnyaneshwar S. Raut, Vaibhav P. Mhaindarkar and Mohamad I. Khan
Org. Biomol. Chem., 2011, 9, 5407-5413 (Cover Page Article)
A novel one-pot route for the synthesis of benzodiazepinyl phosphonates (BDPs) has been achieved. FeCl3 efficiently catalyzed four-component condensation of diamines, acetone and phosphites in the presence of molecular sieves to furnish BDPs as novel chemical entities with good yield. The synthesized BDPs have shown significant protease inhibition activity against clostripain, a disease model for gas gangrene, suggesting that these novel chemical entities could be further explored as cysteine protease inhibitors.
Synthesis of the Antibacterial Benzoquinone Primin and its Water-Soluble Analogue, Primin Acid
Asish K. Bhattacharya*, Tanpreet Kaur and Krishna N. Ganesh
Synthesis 2010 (7): 1141-1144
The biologically active natural product, primin and its water-soluble acid analogue, primin acid are prepared in 34% and 25% overall yields, respectively, from a common intermediate using a Grignard reaction and a Johnson-Claisen rearrangement as the key steps.
Synthesis and in vitro study of 14-aryl-14H-dibenzo[a.j]xanthenes as cytotoxic agents
Asish K. Bhattacharya*, Kalpeshkumar C. Rana, Mohammad Mujahid, Irum Sehar and Ajit K. Saxena
Bioorg. Med. Chem. Lett. 19 (2009) 5590–5593
A simple and expedient method for the synthesis of a series of 14-aryl-14H-dibenzo[a.j]xanthenes is described through a one-pot condensation of b-naphthol with aryl aldehydes catalysed by TaCl5 under solvent-free conventional heating. The major advantages of the present method are: high yields, less reaction time, solvent-free condition and easy purification of the products. The synthesized 14-aryl14H-dibenzo[a.j]xanthenes were evaluated against a panel of six human cancer lines of different tissues. Synthesized compound 3o showed IC50 of 37.9 and 41.3 lM against Colo-205 and 502713, respectively, whereas 3g showed IC50 of 41.9 lM against Colo-205.
Amberlite-IR 120 catalyzed three-component synthesis of α-amino phosphonates in one-pot
Asish K. Bhattacharya* and Kalpeshkumar C. Rana
Tetrahedron Letters 49 (2008) 2598–2601
A simple, efficient, and environmentally benign method for a three-component reaction of an amine, an aldehyde or a ketone, and diethyl phosphite catalyzed by Amberlite-IR 120 resin has been developed to afford a-amino phosphonates in high yields and short reaction times under solvent-free reaction conditions. The major advantages of the present method are good yields, inexpensive, ecofriendly and reusable catalyst, mild and solvent-free reaction conditions and tolerance towards various functionalities present in the substrates.
Asish K. Bhattacharya,* Mamadou A. Diallo and Krishna N.Ganesh
Synthetic Communication, 38: 1518–1526, 2008
Antimony trichloride has been found to be an efficient and expedient catalyst for the acylation of alcohols, phenols, amines, and sugars with acetic anhydride in high yields and in a short reaction time under solvent-free conditions at room temperature. Also, racemization of chiral alcohols and epimerization of sugars were not observed in any of the substrates.
An Efficient Method for the Synthesis of Acylals from Aldehydes under Solvent‐Free Conditions Catalyzed by
Antimony Trichloride
Asish K. Bhattacharya,* Mohammad Mujahid and Arvind A. Natu
Synthetic Communicationsw, 38: 128–134, 2008
A mild and efficient method has been developed for the preparation ofacylals from aldehydes catalyzed by antimony trichloride under solvent-free conditionsin very good to excellent yields. The easy availability, low cost, and ease of handling ofthe catalyst make this procedure especially attractive for large-scale synthesis.
An Efficient One-Pot Synthesis of α-Amino Phosphonates Catalyzed by Bismuth Nitrate Pentahydrate
Asish K. Bhattacharya* and Tanpreet Kaur
SYNLETT 2007, 5, 0745–0748
A simple, efficient, and environmentally benign method has been developed for the synthesis of a-amino phosphonates through a one-pot reaction of aldehydes with amines and diethyl phosphite in the presence of bismuth nitrate pentahydrate as a catalyst. Some of the major advantages of this protocol are: good yields, the involvement of a less-expensive and non-toxic catalyst, mild and solvent-free reaction conditions and also tolerance towards other functional groups present in the substrates. Eighteen examples are described, highlighting the substrate scope of the reaction.
Asish K. Bhattacharya* and Kalpeshkumar C. Rana
Mendeleev Commun., 2007, 17, 247–248
The synthesis of 14-aryl-14H-dibenzo[a.j]xanthenes is described through a one-pot condensation of β-naphthol with aryl aldehydes in the presence of methanesulfonic acid as the catalyst under solvent-free conditions using microwave irradiation.
Synthesis of a novel plant growth promoter from gallic acid
Arvind Singh Negi, Mahinder P. Darokar, Sunil K. Chattopadhyay, Ankur Garg, Asish K. Bhattacharya, Vandana Srivastava and Suman P. S. Khanuja
Bioorganic & Medicinal Chemistry Letters 15 (2005) 1243–1247
Gallic acid has been modified to naphthophenone derivatives with esterified fatty acid side chain. Compound 12, an ethyl crotonate ester of naphthophenone derivative has shown potent auxin like growth promoter activity. This is the first example of naphthophenone derivatives with plant growth promoting activity. 2005 Elsevier Ltd. All rights reserved.
A Simple Regioselective Demethylation of p‐Aryl Methyl Ethers Using Aluminum Chloride‐Dichloromethane System
Arvind S. Negi, Sunil K. Chattopadhyay, Sachin Srivastava and Asish K. Bhattacharya
Synthetic Communicationsw, 35: 15–21, 2005
Several aryl methyl ethers of phenolic esters and diaryl ketones have beenselectively demethylated to their corresponding 4-hydroxy derivatives by usingaluminium chloride-dichloromethane system at room temperature in good yields(53–85%).
Betuligenol derivative with growth inhibition and antifeedant activity
Sunil K. Chattopadhyay, Sachin Srivastava, Koneni V. Sashidhara, Arun K. Tripathi, Asish K. Bhattacharya and Arvind S. Negi
Bioorg. Med. Chem. Lett. 14 (2004) 1729–1731
The title chiral amine, 3-(4-methoxyphenyl)-1-methylpropylamine 5 has been synthesized fromnaturally abundant betuligenol 1 in three steps and also in good yield. Furthermore, the versatile intermediate 3 could be manipulated for the preparation of chiral disulphide 7. The amine derivative 5 prepared from(-)-betuligenol showed significant growth inhibition and antifeedant activity.