01048nas a2200181 4500008004100000022001400041245008100055210006900136260000900205300001400214490000700228520042500235100002100660700001900681700002800700700002800728856011000756 2019 eng d a1144-054600aSynthesis of artemisinin derived glycoconjugates inspired by click chemistry0 aSynthesis of artemisinin derived glycoconjugates inspired by cli cMAR  a4017-40210 v433 a

Herein we describe the synthesis of artemisinin based glycoconjugates (9a-i) through employing a Cu(i)-catalysed reaction between -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.

1 aGoswami, Lakshmi1 aPaul, Sayantan1 aKotammagari, Tharun, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/synthesis-artemisinin-derived-glycoconjugates-inspired-click-chemistry01409nas a2200169 4500008004100000022001400041245013700055210006900192260000800261300001600269490000600285520074200291100002801033700001901061700002801080856013101108 2019 eng d a2470-134300aUnusual epimerization in styryllactones: synthesis of (-)-5-hydroxygoniothalamin, (-)-5-acetylgoniothalamin, and O-TBS-goniopypyrone0 aUnusual epimerization in styryllactones synthesis of 5hydroxygon cDEC a22549-225560 v43 a

(-)-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.

1 aKotammagari, Tharun, K.1 aPaul, Sayantan1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/unusual-epimerization-styryllactones-synthesis-5-hydroxygoniothalamin-5-acetylgoniothalamin01887nas a2200193 4500008004100000022001400041245008700055210006900142260000800211300001400219490000700233520121500240100002801455700001901483700002201502700002201524700002801546856011901574 2020 eng d a1477-052000aSynthesis of artemisinic acid derived glycoconjugates and their anticancer studies0 aSynthesis of artemisinic acid derived glycoconjugates and their  cMAR a2252-22630 v183 a

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.

1 aKotammagari, Tharun, K.1 aPaul, Sayantan1 aBarik, Ganesh, K.1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/synthesis-artemisinic-acid-derived-glycoconjugates-and-their-anticancer-studies02281nas a2200193 4500008004100000245013400041210006900175260000800244300001200252490000700264520155200271100002101823700001801844700001901862700002001881700002601901700002801927856013201955 2022 eng d00aDesign and synthesis of eugenol/isoeugenol glycoconjugates and other analogues as antifungal agents against Aspergillus fumigatus0 aDesign and synthesis of eugenolisoeugenol glycoconjugates and ot cAUG a955-9620 v133 a

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 mu M). 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 double bond of eugenol and subsequent azidation of a primary alcohol followed by intramolecular coupling reactions leading to various other analogues. All the synthesized compounds were assayed against an opportunistic pathogenic fungus, Aspergillus fumigatus. Among the synthesized compounds, two analogues have exhibited significant antifungal activities with IC50 values of 5.42 and 9.39 mu M, respectively. The study suggested that these two analogues inhibit cell wall-associated melanin hydrophobicity along with the number of conidia. The synthesized compounds were found to be non-cytotoxic to an untransformed cell line.

1 aGoswami, Lakshmi1 aGupta, Lovely1 aPaul, Sayantan1 aVermani, Maansi1 aVijayaraghavan, Pooja1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/design-and-synthesis-eugenolisoeugenol-glycoconjugates-and-other-analogues-antifungal-agents01599nas a2200277 4500008004100000022001400041245011400055210006900169260000800238300001200246490000700258520068200265653001700947653001800964653002000982653001601002653001901018100002801037700001701065700001901082700001801101700002401119700002201143700002801165856012801193 2023 eng d a1860-539700aAccelerated Rauhut-Currier dimerization enabled the synthesis of (+/-)-incarvilleatone and anticancer studies0 aAccelerated RauhutCurrier dimerization enabled the synthesis of  cFEB a204-2110 v193 a

The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut-Currier (RC) dimeriza-tion. The other key steps of the synthesis are oxa-Michael 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 X-ray analysis. In addition, a one-pot synthesis of (+/-)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells nonetheless, they exhibited very limited growth suppression activity.

10adimerization10aincarviditone10aincarvilleatone10aoxa-Michael10aRauhut-Currier1 aKotammagari, Tharun, K.1 aMisra, Sweta1 aPaul, Sayantan1 aKunte, Sunita1 aGonnade, Rajesh, G.1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/accelerated-rauhut-currier-dimerization-enabled-synthesis-incarvilleatone-and-anticancer02318nas a2200253 4500008004100000022001400041245009700055210006900152260000900221490000700230520148500237653000601722653001301728653002201741653002601763653002301789653001501812100002101827700001801848700001901866700002601885700002801911856012501939 2023 eng d a1860-717900aDesign and synthesis of 1,3-diynes as potent antifungal agents against aspergillus fumigatus0 aDesign and synthesis of 13diynes as potent antifungal agents aga cMAY 0 v183 a

Eugenol and isoeugenol, secondary metabolites isolated from the plant Myristica fragrans have displayed antifungal activities against Aspergillus fumigatus (IC50 1900 mu M). Compounds having conjugated unsaturation have been of great use as antifungals i. e. amphotericin B, nystatin and terbinafine etc. Hence, in the present study, we have designed and synthesised 1,3-diynes by utilizing Glaser-Hay and Cadiot-Chodkiewicz coupling reactions to furnish possible antifungal agents. Synthesis of 1,6-diphenoxyhexa-2,4-diyne derivatives was achieved by Cu(I) catalysed coupling of propargylated eugenol, isoeugenol, guaiacol, vanillin and dihydrogenated eugenol or eugenol in good to excellent yields. All the synthesized compounds were evaluated against pathogenic fungus A. fumigatus. Among all the synthesized compounds, one of the compounds was found to be exhibiting promising antifungal activity with IC50 value of 7.75 mu M thereby suggesting that this type of scaffold could pave the way for developing new antifungal agents. The most active compound was found to be low cytotoxic when assayed against L-132 cancer cell line. Effect of the most active compound on ergosterol biosynthesis has also been studied. Also, the most active compound exhibited significant anti-biofilm activity although the concentration was found to be higher than its anti-fungal activity. Morphological changes in the biofilm were remarkable under confocal laser scanning microscopy.

10a110a3-Diynes10aAntifungal agents10aAspergillus fumigatus10aCadiot-Chodkiewicz10aGlaser-Hay1 aGoswami, Lakshmi1 aGupta, Lovely1 aPaul, Sayantan1 aVijayaraghavan, Pooja1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/design-and-synthesis-13-diynes-potent-antifungal-agents-against-aspergillus-fumigatus02115nas a2200217 4500008004100000022001400041245016000055210006900215260000900284490000700293520129800300653001701598653002101615653001601636653002601652653001701678100001901695700002701714700003101741856012501772 2023 eng d a1861-472800aLate-stage C(sp(2))-H arylation of artemisinic acid and arteannuin B: effect of olefin migration towards synthesis of C-13 arylated artemisinin derivatives0 aLatestage Csp2H arylation of artemisinic acid and arteannuin B e cAPR 0 v183 a

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 ring-contracted rearranged product. Additionally, we have extended our developed protocol for C-13 arylation of arteannuin B, a sesquiterpene lactone epoxide considered to be the biogenetic precursor of artemisinic acid. Indeed, the synthesis of C-13 arylated arteannuin B renders our developed protocol to be effective in sesquiterpene lactone as well.

10aArteannuin B10aArtemisinic acid10aartemisinin10aC-H functionalization10aPd-catalysis1 aPaul, Sayantan1 aGhodake, Balaji, M. M.1 aBhattacharya, Asish, K. K. uhttps://library.ncl.res.in/content/late-stage-csp2-h-arylation-artemisinic-acid-and-arteannuin-b-effect-olefin-migration01254nas a2200181 4500008004100000022001400041245008300055210006900138260000800207300001400215490000700229520063600236100002100872700001900893700002400912700002800936856010800964 2024 eng d a1477-052000a1,6-Conjugate addition of in situ generated aryldiazenes to p-quinone methides0 a16Conjugate addition of in situ generated aryldiazenes to pquino cJUL a5636-56450 v223 a

Herein we report a transition-metal free, base-mediated 1,6-conjugate addition of aryldiazenes to para-quinone 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.

1 aMamale, Ajay, G.1 aPaul, Sayantan1 aGonnade, Rajesh, G.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/16-conjugate-addition-situ-generated-aryldiazenes-p-quinone-methides01936nas a2200241 4500008004100000022001400041245014800055210006900203260000800272490000700280520105400287653003201341653003001373653002501403653001201428653001501440100002101455700001901476700002101495700002401516700002801540856012601568 2024 eng d a2193-580700aMethanesulfonic acid-catalyzed friedel-crafts alkylation: towards sustainable synthesis of arylalkanes from donor-acceptor cyclopropane ketones0 aMethanesulfonic acidcatalyzed friedelcrafts alkylation towards s cJUL0 v133 a

We present herein Br & oslash;nsted 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. The presence of 1,4-diphenyl butan-1-one and 1,3-diphenyl propane-1-one motifs in various naturally occurring biologically significant molecules prompted us to develop a Br & oslash;nsted acid-catalyzed Friedel-Crafts alkylation of phenols with Donor-Acceptor cyclopropane. image

10adonor-acceptor cyclopropane10aFriedel-Crafts alkylation10amethanesulfonic acid10aPhenols10athiophenol1 aGoswami, Lakshmi1 aPaul, Sayantan1 aMamale, Ajay, G.1 aGonnade, Rajesh, G.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/methanesulfonic-acid-catalyzed-friedel-crafts-alkylation-towards-sustainable-synthesis01114nas a2200217 4500008004100000022001400041245008600055210006900141260000900210300001200219490000700231520042200238653002300660653001700683653001300700653001800713653001400731100001900745700002800764856010400792 2024 eng d a1083-616000aShort review on the synthetic routes for the antiepileptic drug (S)-levetiracetam0 aShort review on the synthetic routes for the antiepileptic drug  cMAR  a924-9360 v283 a

Epilepsy is a chronic disorder characterized by recurrent unpredictable seizures. Levetiracetam (Keppra) was introduced by UCB for the treatment of partial onset seizures in patients above 16 years of age diagnosed with epilepsy. This review reports synthetic strategies available for the synthesis of (S)-levetiracetam and will certainly aid the quest for the development of new routes for its synthesis.

10aantiepileptic drug10abutyrolactam10aepilepsy10alevetiracetam10asynthesis1 aPaul, Sayantan1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/short-review-synthetic-routes-antiepileptic-drug-s-levetiracetam01750nas a2200229 4500008004100000022001400041245009200055210006900147260000800216300001500224490000600239520100200245653001501247653001401262653001601276653001101292653002601303100002401329700001901353700002801372856012001400 2024 eng d a2365-654900aStrategies employing transition-metal free conditions for C-C bond formation in indoles0 aStrategies employing transitionmetal free conditions for CC bond cSEP ae2024032800 v93 a

Indole motifs are omnipresent in nature and can be found in many natural products as well as pharmaceuticals. It is for this reason synthetic transformations of indole have become a topic of interest for the organic and medicinal chemist community for decades. In this review, we have emphasized the functionalization of indoles via transition-metal-free approaches. This review touches on many aspects in different sub-sections, which gives a proposition of the tactics employed for the functionalization of indoles and an overview of the road ahead. 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. image

10aAlkylation10aArylation10aformylation10aIndole10atransition-metal free1 aGhodake, Balaji, M.1 aPaul, Sayantan1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/strategies-employing-transition-metal-free-conditions-c-c-bond-formation-indoles01407nas a2200241 4500008004100000022001400041245013600055210006900191260000800260300001500268490000700283520054400290653002300834653002900857653002900886653001700915653001800932100001900950700001900969700002200988700002801010856012701038 2025 eng d a2365-654900aCyclopropane containing triterpenoids, cycloartenone, and cycloartenol: isolation, chemical transformations, and anticancer studies0 aCyclopropane containing triterpenoids cycloartenone and cycloart cMAR ae2024036980 v103 a

Cycloartenone and cycloartenol, two plant-derived triterpenoids possessing cyclopropane ring were isolated from the latex of Artocarpus heterophyllus (jackfruit). Cycloartenol was chemically modified to synthesize dihydrocycloartenol via acetylation and deacetylation methodology followed by hydrogenation. Hydroxyl group present in the cycloartenol was also employed for the nitro benzoate formation. All the isolated and synthesized compounds were assayed against MCF7 breast cancer cell line for their anticancer properties.

10aAnticancer studies10aArtocarpus heterophyllus10aChemical transformations10aCycloartenol10aCycloartenone1 aPaul, Sayantan1 aMandal, Kartik1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/cyclopropane-containing-triterpenoids-cycloartenone-and-cycloartenol-isolation-chemical