| ORIGINAL ARTICLES |
|
|
|
|
|
Chemically engineered essential oils prepared through thiocyanation under solvent-free conditions: chemical and bioactivity alteration |
| Liz E. Lescano1, Mario O. Salazar1,2, Ricardo L. E. Furlan1,2 |
1. Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Suipacha 531, 2000, Rosario, Argentina;
2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Suipacha 531, 2000, Rosario, Argentina |
|
|
|
|
Abstract The generation of chemically engineered essential oils (CEEOs) prepared from bi-heteroatomic reactions using ammonium thiocyanate as a source of bioactive compounds is described. The impact of the reaction on the chemical composition of the mixtures was qualitatively demonstrated through GC-MS, utilizing univariate and multivariate analysis. The reaction transformed most of the components in the natural mixtures, thereby expanding the chemical diversity of the mixtures. Changes in inhibition properties between natural and CEEOs were demonstrated through acetylcholinesterase TLC autography, resulting in a threefold increase in the number of positive events due to the modification process. The chemically engineered Origanum vulgare L. essential oil was subjected to bioguided fractionation, leading to the discovery of four new active compounds with similar or higher potency than eserine against the enzyme. The results suggest that the directed chemical transformation of essential oils can be a valuable strategy for discovering new acetylcholinesterase (AChE) inhibitors.
|
| Keywords
Chemically modified essential oils
Ammonium thiocyanate
Iodine catalysis
Bioactive compounds
Acetylcholinesterase inhibitors
|
| Fund:Ricardo L. E. Furlan and Mario O. Salazar would like to acknowledge for provided financial support by Universidad Nacional de Rosario (80020180300114UR and 80020180100128UR), CONICET (PIP No 11220200102423) and FONCYT (PICT2015-3574 and PICT2018-01554) for the development of this work. |
|
Corresponding Authors:
Mario O. Salazar,E-mail:msalazar@fbioyf.unr.edu.ar
E-mail: msalazar@fbioyf.unr.edu.ar
|
|
Issue Date: 14 October 2024
|
|
|
[1] Karageorgis G, Warriner S, Nelson A. Efficient discovery of bioactive scaffolds by activity-directed synthesis. Nat Chem. 2014;6:872-6. https://doi.org/10.1038/nchem.2034.
[2] Young RJ, Flitsch SL, Grigalunas M, Leeson PD, Quinn RJ, Turner NJ, Waldmann H. The time and place for nature in drug discovery. JACS Au. 2022;2:2400-16. https://doi.org/10.1021/jacsau.2c00415.
[3] Jalota K, Sharma V, Agarwal C, Jindal S. Eco-friendly approaches to phytochemical production: elicitation and beyond. Nat Prod Bioprospect. 2024;14:5. https://doi.org/10.1007/s13659-023-00419-7.
[4] Raut JS, Karuppayil SM. A status review on the medicinal properties of essential oils. Ind Crops Prod. 2014;62:250-64. https://doi.org/10.1016/J.INDCROP.2014.05.055.
[5] Sell CS. The Chemistry of Fragrance. In Perfumer to Consumer. 2nd ed. The Royal Society of Chemistry; Cambridge, UK. 2006, p. 329.
[6] Liu Z, Wang M, Wu M, Li X, Liu H, Li S, Chen L. Volatile organic compounds (VOCs) from plants: from release to detection. Trends Anal Chem. 2023;158: 116872. https://doi.org/10.1016/j.trac.2022.116872.
[7] Maffei ME, Gertsch J, Appendino G. Plant volatiles: production, function and pharmacology. Nat Prod Rep. 2011;28:1359-80. https://doi.org/10.1039/C1NP00021G.
[8] Li G, Lou H-X. Strategies to diversify natural products for drug discovery. Med Res Rev. 2018;38:1255-94. https://doi.org/10.1002/med.21474.
[9] Yao H, Liu J, Xu S, Zhu Z, Xu J. The structural modification of natural products for novel drug discovery. Expert Opin Drug Discov. 2017;12:121-40. https://doi.org/10.1080/17460441.2016.1272757.
[10] Atanasov AG, Zotchev SB, Dirsch VM, the International Natural Product Sciences Taskforce, Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20:200-16. https://doi.org/10.1038/s41573-020-00114-z.
[11] Mahal A, Wu P, Jiang Z-H, Wei X. Synthesis and cytotoxic activity of novel tetrahydrocurcumin derivatives bearing pyrazole moiety. Nat Prod Bioprospect. 2017;7:461-9. https://doi.org/10.1007/s13659-017-0143-9.
[12] Bankeu JJK, Sattar H, Fongang YSF, Muhammadi SW, Simoben CV, Ntie-Kang F, Feuya GRT, Tchuenmogne MAT, Lateef M, Lenta BN, Ali MS, Ngouela AS. Synthesis, urease inhibition and molecular modelling studies of novel derivatives of the naturally occurring β-Amyrenone. Nat Prod Bioprospect. 2021;9:49-59. https://doi.org/10.1007/s13659-018-0193-7.
[13] Wang Y, Zhang M, Zhou X, Xu C, Zhu C, Yuan Y, Chen N, Yang Y, Guo Q, Shi J. Insight into medicinal chemistry behind traditional Chinese Medicines: p-Hydroxybenzyl alcohol-derived dimers and trimers from Gastrodia elata. Nat Prod Bioprospect. 2021;11:31-50. https://doi.org/10.1007/s13659-020-00258-w.
[14] Deng X, Huang S-L, Ren J, Pan Z-H, Shen Y, Zhou H-F, Zuo Z-L, Leng Y, Zhao Q-S. Development and structure-activity relationships of tanshinones as selective 11ß-hydroxysteroid dehydrogenase 1 inhibitors. Nat Prod Bioprospect. 2022;12:36. https://doi.org/10.1007/s13659-022-00358-9.
[15] Lopez SN, Ramallo IA, Gonzalez Sierra M, Zacchino SA, Furlan RLE. Chemically engineered extracts as an alternative source of bioactive natural product-like compounds. Proc Natl Acad Sci USA. 2007;104:441-4. https://doi.org/10.1073/pnas.0608438104.
[16] Ramallo IA, Salazar MO, García P, Furlan RLE. Chemical Diversification of Natural Product Extracts, In Studies in Natural Products Chemistry, Vol. 60; Atta-ur-Rahman, Ed. Elsevier: Amsterdam, 2018, Chapter 10.
[17] Ramallo IA, Salazar MO, Mendez L, Furlan RLE. Chemically engineered extracts: source of bioactive compounds. Acc Chem Res. 2011;44:241-50. https://doi.org/10.1021/ar100106n.
[18] Solís CM, Salazar MO, Ramallo IA, García P, Furlan RLE. A tyrosinase inhibitor from a nitrogen-enriched chemically engineered extract. ACS Comb Sci. 2019;21:622-7. https://doi.org/10.1021/acscombsci.9b00064.
[19] Salazar MO, Ramallo IA, Micheloni O, Gonzalez Sierra M, Furlan RLE. Chemically engineered extracts: bioactivity alteration through sulfonylation. Bioorg Med Chem Lett. 2009;19:5067-70. https://doi.org/10.1016/j.bmcl.2009.07.038.
[20] Salazar MO, Micheloni O, Escalante AM, Furlán RLE. Discovery of a β-glucosidase inhibitor from a chemically engineered extract prepared through sulfonylation. Mol Divers. 2011;15:713-9. https://doi.org/10.1007/s11030-010-9301-2.
[21] Salazar MO, Osella MI, Arcusin DEJ, Lescano LE, Furlán RLE. New α-glucosidase inhibitors from a chemically engineered essential oil of Origanum vulgare L. Ind Crops Prod. 2020;156: 112855. https://doi.org/10.1016/j.indcrop.2020.112855.
[22] Mendez L, Salazar MO, Ramallo IA, Furlan RLE. Brominated extracts as source of bioactive compounds. ACS Comb Sci. 2011;13:200-4. https://doi.org/10.1021/co100073k.
[23] García P, Ramallo IA, Salazar MO, Furlan RLE. Chemical diversification of essential oils, evaluation of complex mixtures and identification of a xanthine oxidase inhibitor. RSC Adv. 2016;6:57245-52. https://doi.org/10.1039/C6RA05373D.
[24] García P, Salazar MO, Ramallo IA, Furlan RLE. A new fluorinated tyrosinase inhibitor from a chemically engineered essential oil. ACS Comb Sci. 2016;18:283-6. https://doi.org/10.1021/acscombsci.6b00004.
[25] Adessi TG, Ana Y, Stempin CC, García MC, Bisogno FR, Nicotra VE, García ME. Psilostachyins as trypanocidal compounds: bioguided fractionation of Ambrosia tenuifolia chemically modified extract. Phytochem. 2022;194: 113014. https://doi.org/10.1016/j.phytochem.2021.113014.
[26] Du Y, Sun J, Gong Q, Wang Y, Fu P, Zhu W. New α-pyridones with quorum-sensing inhibitory activity from diversity-enhanced extracts of a Streptomyces sp. derived from marine algae. J Agric Food Chem. 2018;66:1807-12. https://doi.org/10.1021/acs.jafc.7b05330.
[27] Guo Q, Chen J, Ren Y, Yin Z, Zhang J, Yang B, Wang X, Yin W, Zhang W, Ding G, Chen L. Hydrazine-containing heterocycle cytochalasan derivatives from hydrazinolysis of extracts of a desert soil-derived fungus Chaetomium madrasense 375. Front Chem. 2021;9: 620589. https://doi.org/10.3389/fchem.2021.620589.
[28] He W, Xu Y, Wu D, Wang D, Gao H, Wang L, Zhu W. New alkaloids from the diversity-enhanced extracts of an endophytic fungus Aspergillus flavus GZWMJZ-288. Bioorg Chem. 2021;107: 104623. https://doi.org/10.1016/j.bioorg.2020.104623.
[29] Kamauchi H, Noji M, Kinoshita K, Takanami T, Koyama K. Coumarins with an unprecedented tetracyclic skeleton and coumarin dimers from chemically engineered extracts of a marine-derived fungus. Tetrahedron. 2018;74:2846-e2856. https://doi.org/10.1016/j.tet.2018.04.033.
[30] Kikuchi H, Kawai K, Nakashiro Y, Yonezawa T, Kawaji K, Kodama EN, Oshima Y. Construction of a meroterpenoid-like compounds library based on diversity-enhanced extracts. Chem Eur J. 2019;25:1106-12. https://doi.org/10.1002/chem.201805417.
[31] Lin Z, Ma X, Wei H, Li D, Gu Q, Zhu T. Spicarins A-D from acetylated extract of fungus Spicaria elegans KLA03. RSC Adv. 2015;5:35262-6. https://doi.org/10.1039/C5RA01923K.
[32] Nalli Y, Mir KB, Amin T, Gennedi V, Jameel E, Goswami A, Ali A. Divergent synthesis of fractionated Cannabis sativa extract led to multiple cannabinoids C-&O-glycosides with antiproliferative/anti-metastatic properties. Bioorg Chem. 2024;143: 107030. https://doi.org/10.1016/j.bioorg.2023.107030.
[33] Navarro Del Hierro J, Casado-Hidalgo G, Reglero G, Martin D. The hydrolysis of saponin-rich extracts from fenugreek and quinoa improves their pancreatic lipase inhibitory activity and hypocholesterolemic effect. Food Chem. 2021;338: 128113. https://doi.org/10.1016/j.foodchem.2020.128113.
[34] Ortega CA, Favier LS, Cifuente DA. Chemical derivatization of natural extracts obtained from Larrea divaricata Cav. increase in the antioxidant activity and protein precipitating capacity. AJSR. 2017;5:197-202. https://doi.org/10.15413/ajsr.2017.0412.
[35] Ramallo IA, Alonso VL, Rua F, Serra E, Furlan RLE. A bioactive Trypanosoma cruzi bromodomain inhibitor from chemically engineered extracts. ACS Comb Sci. 2018;20:220-8. https://doi.org/10.1021/acscombsci.7b00172.
[36] Ray B, Ali I, Jana S, Mukherjee M, Pal S, Ray S, Schütz M, Marschall M. Antiviral strategies using natural source-derived sulfated polysaccharides in the light of the COVID-19 pandemic and major human pathogenic viruses. Viruses. 2022;14:35. https://doi.org/10.3390/v14010035.
[37] Righi D, Marcourt L, Koval A, Ducret V, Pellissier L, Mainetti A, Katanaev VL, Perron K, Wolfender J-L, Ferreira QE. Chemo-diversification of plant extracts using a generic bromination reaction and monitoring by metabolite profiling. ACS Comb Sci. 2019;21:171-82. https://doi.org/10.1021/acscombsci.8b00132.
[38] Salazar MO, Osella MI, Ramallo IA, Furlan RLE. Nα-arylsulfonyl histamines as selective β-glucosidase inhibitors. RSC Adv. 2018;8:36209-18. https://doi.org/10.1039/C8RA06625F.
[39] Sulistyowaty MI, Uyen NH, Suganuma K, Chitama B-YA, Yahata K, Kaneko O, Sugimoto S, Yamano Y, Kawakami S, Otsuka H, Matsunami K. Six new phenylpropanoid derivatives from chemically converted extract of Alpinia galanga (L.) and their antiparasitic activities. Molecules. 2021;26:1756. https://doi.org/10.3390/molecules26061756.
[40] Tan Y, Sun X, Dong F, Tian H, Jiang R. Enhancing the structural diversity and bioactivity of natural products by combinatorial modification exemplified by total tanshinones. Chin J Chem. 2015;33:1084-8. https://doi.org/10.1002/cjoc.201500276.
[41] Tomohara K, Ohashi N, Uchida T, Nose T. Enhancing the structural diversity and bioactivity of natural products by combinatorial modification exemplified by total tanshinones. Sci Rep. 2022;12:15568. https://doi.org/10.1038/s41598-022-19579-6.
[42] Zhang J-L, Xu W, Zhou Z-R, Li J, Jiang L-L, Zhang X-X, Jiang R-W. Antineoplastic constituents from the chemical diversified extract of Radix puerariae. Chem Biodiversity. 2019;16: e1800408. https://doi.org/10.1002/cbdv.201800408.
[43] Suzuki Y, Ichinohe K, Sugawara A, Kida S, Zhang J, Yamada O, Hattori T, Oshima Y, Murase S, Kikuchi H. Development of indole alkaloid-type dual immune checkpoint inhibitors against CTLA-4 and PD-L1 based on diversity-enhanced extracts. Front Chem. 2021;9: 766107. https://doi.org/10.3389/fchem.2021.766107.
[44] Beato A, Haudecoeur R, Boucherle B, Peuchmaur M. Expanding chemical frontiers: approaches for generating diverse and bioactive natural product-like compounds libraries from extracts. Chem Eur J. 2024;30: e202304166. https://doi.org/10.1002/chem.202304166.
[45] Henkel T, Brune RM, Müller H, Reichel F. Statistical investigation into the structural complementarity of natural products in comparison with synthetic compounds. Angew Chem Int Ed Engl. 1999;38:643-7. https://doi.org/10.1002/(SICI)1521-3773(19990301)38:5%3c643::AID-ANIE643%3e3.0.CO;2-G.
[46] Ertl P, Schuhmann T. A systematic cheminformatics analysis of functional groups occurring in natural products. J Nat Prod. 2019;82:1258-63. https://doi.org/10.1021/acs.jnatprod.8b01022.
[47] Petkowski JJ, Bains W, Seager S. Natural products containing a nitrogen-sulfur bond. J Nat Prod. 2018;81:423-46. https://doi.org/10.1021/acs.jnatprod.7b00921.
[48] Karmaker PG, Alam MdA, Huo F. Recent advances in photochemical and electrochemically induced thiocyanation: a greener approach for SCN-containing compound formation. RSC Adv. 2022;12:6214-33. https://doi.org/10.1039/d1ra09060g.
[49] Vekariya RH, Patel HD. α-thiocyanation of carbonyl compounds: a review. Synth Commun. 2017;47:87-104. https://doi.org/10.1080/00397911.2016.1255973.
[50] Majedi S, Sreerama L, Vessally E, Behmagham F. Metal-free regioselective thiocyanation of (hetero) aromatic CH bonds using ammonium thiocyanate: an overview. J Chem Lett. 2020;1:25-31. https://doi.org/10.22034/JCHEMLETT.2020.107760.
[51] Castanheiro T, Suffert J, Donnard M, Gulea M. Recent advances in the chemistry of organic thiocyanates. Chem Soc Rev. 2016;45:494-505. https://doi.org/10.1039/c5cs00532a.
[52] Gulea M, Donnard M. Sustainable synthetic approaches involving thiocyanation and sulfur-cyanation: an update. Curr Green Chem. 2020;7:201-16. https://doi.org/10.2174/2213346107999200616105745.
[53] Sarkar A, Santra S, Kundu SK, Hajra A, Zyryanov GV, Chupakhin ON, Charushin VN, Majee A. A decade update on solvent and catalyst-free neat organic reactions: a step forward towards sustainability. Green Chem. 2016;18:4475-525. https://doi.org/10.1039/c6gc01279e.
[54] Zangade S, Patil P. A review on solvent-free methods in organic synthesis. Curr Org Chem. 2019;23:2295-318. https://doi.org/10.2174/1385272823666191016165532.
[55] Yadav JS, Subba Reddy BV, Shubashree S, Sadashiv K. Iodine/MeOH: a novel and efficient reagent system for thiocyanation of aromatics and heteroaromatics. Tetrahedron Lett. 2004;45:2951-4. https://doi.org/10.1016/j.tetlet.2004.02.073.
[56] Yadav JS, Subba Reddy BV, Subba Reddy UV, Krishna AD. Iodine/MeOH as a novel and versatile reagent system for the synthesis of a-ketothiocyanates. Tetrahedron Lett. 2007;48:5243-6. https://doi.org/10.1016/j.tetlet.2007.05.143.
[57] Kharbach M, Marmouzi I, El Jemli M, Bouklouze A, Heyden YV. Recent advances in untargeted and targeted approaches applied in herbal-extracts and essential-oils fingerprinting - a review. J Pharm Biomed Anal. 2020;177: 112849. https://doi.org/10.1016/j.jpba.2019.112849.
[58] Tan ECK, Johnell K, Garcia-Ptacek S, Haaksma ML, Fastbom J, Bell JS, Eriksdotter M. Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia. Alzheimer’s & Dementia. 2018;14:944-51. https://doi.org/10.1016/j.jalz.2018.02.0111552-5260.
[59] Karunakaran KB, Thiyagaraj A, Santhakumar K. Novel insights on acetylcholinesterase inhibition by Convolvulus pluricaulis, scopolamine and their combination in zebraish. Nat Prod Bioprospect. 2022;12:6. https://doi.org/10.1007/s13659-022-00332-5.
[60] dos Santos TC, Gomes TM, Serra Pinto BA, Camara AL, de Andrade Paes AM. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol. 2018;9:1192. https://doi.org/10.3389/fphar.2018.01192.
[61] Ramallo IA, Salazar MO, Furlan RLE. Thin layer chromatography-autography-high resolution mass spectrometry analysis: accelerating the identification of acetylcholinesterase inhibitors. Phytochem Anal. 2015;26:404-12. https://doi.org/10.1002/pca.2574.
[62] Cabezudo I, Salazar MO, Ramallo IA, Furlán RLE. Effect-directed analysis in food by thin-layer chromatography assays. Food Chem. 2022;390: 132937. https://doi.org/10.1016/j.foodchem.2022.132937.
[63] Pezzani R, Vitalini S, Iriti M. Bioactivities of Origanum vulgare L.: an update. Phytochem Rev. 2017;16:1253-68. https://doi.org/10.14500/aro.10085.
[64] Lin Q, Yang W, Yao Y, Chen S, Tan Y, Chen D, Yang D. Copper-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes leading to β-thiocyanato thioethers. Org Lett. 2019;21:7244-7. https://doi.org/10.1021/acs.orglett.9b02452.
[65] Chen H, Jiang W, Zeng Q. Recent advances in synthesis of chiral thioethers. J Chem Rec. 2020;20:1-29. https://doi.org/10.1002/tcr.202000084.
[66] Li P, Yang Y, Wang X, Wu X. Recent achievements on the agricultural applications of thioether derivatives: a 2010-2020 decade in review. J Heterocyclic Chem. 2021;58:1225-51. https://doi.org/10.1002/jhet.4234.
[67] Ellman GL, Courtney D, Andres V Jr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95.
[68] Kelly TR, Kim MH, Curtis ADM. Structure correction and synthesis of the naturally occurring benzothiazinone BMY 40662. J Org Chem. 1993;58:5855-7. https://doi.org/10.1021/jo00073a057.
[69] de Oliveira Lima Filho E, Malvestiti I. Mechanochemical thiocyanation of aryl compounds via C-H functionalization. ACS Omega. 2020;5:33329-39. https://doi.org/10.1021/acsomega.0c05131.
[70] Wang Z, Wang L, Chen Q, He M. Rapid and efficient thiocyanation of phenols, indoles, and anilines in 1,1,1,3,3,3-hexafluoro-2-propanol under ultrasound irradiation. Synth Commun. 2018;48:76-84. https://doi.org/10.1080/00397911.2017.1390139.
[71] Mete TB, Khopade TM, Bhat RG. Transition-metal-free regioselective thiocyanation of phenols, anilines and heterocycles. Tetrahedron Lett. 2017;58:415-8. https://doi.org/10.1016/j.tetlet.2016.12.043.
[72] Weng Z, Wang H, Wang L. Efficient thiocyanation of phenols and anilines in the CeBr 3 / H2O2 system. Mendeleev Commun. 2023;33:118-20. https://doi.org/10.1016/j.mencom.2023.01.037.
[73] Dey A, Hajra A. Metal-free synthesis of 2-arylbenzothiazoles from aldehydes, amines, and thiocyanate. Org Lett. 2019;21:1686-9. https://doi.org/10.1021/acs.orglett.9b0245.
[74] US5294724. 4-hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters and a process for their preparation. 03/15/1994.
[75] Dwivedi V, Rajesh M, Kumar R, Kant R, Sridhar RM. A stereoselective thiocyanate conjugate addition to electron deficient alkynes and concomitant cyclization to N, S-heterocycles. Chem Commun. 2017;53:11060-3. https://doi.org/10.1039/c7cc06081e.
[76] Wang C, Geng X, Zhao P, Zhou Y, Wu Y-D, Cui Y-F, Wu A-X. I2/CuCl2-promoted one-pot three-component synthesis of aliphatic or aromatic substituted 1,2,3-thiadiazoles. Chem Commun. 2019;55:8134-7. https://doi.org/10.1039/c9cc04254g.
[77] Kurzer F. 1,2,4-thiadiazoles. Adv Heterocycl Chem. 1982;32:285-398. https://doi.org/10.1016/S0065-2725(08)60656-X.
[78] Kihara Y, Kabashima S, Uno K, Okawara T, Yamasaki T, Furukawa M. Oxidative heterocyclization using diethyl azodicarboxylate. Synthesis. 1990;11:1020-3. https://doi.org/10.1055/s-1990-27081.
[79] Chen M, Lin S, Li L, Zhu C, Wang X, Wang Y, Jiang B, Li Y, Wang S, Yuhuan L, Jiaoliang J, Shi J. Enantiomers of an indole alkaloid containing unusual dihydrothiopyran and 1,2,4-thiadiazole rings from the root of Isatis indigotica. Org Lett. 2012;14:5668-71. https://doi.org/10.1021/ol302660t.
[80] Anstis DG, Davison EK, Sperry J. 1,2,4-Thiadiazole alkaloids-isolation, biological activity and synthesis. Tetrahedron. 2024;150: 133767. https://doi.org/10.1016/j.tet.2023.133767.
[81] Aki S, Fujioka T, Ishigami M, Minamikawa J. A practical synthesis of 3,4-diethoxybenzthioamide based on friedel-crafts reaction with potassium thiocyanate in methanesulfonic acid. Bioorg Med Chem Lett. 2002;12:2317-20. https://doi.org/10.1016/s0960-894x(02)00398-0.
[82] Solís CM, Salazar MO, Ramallo IA, García P, Furlan RLE. Cyclocondensation versus cyclocondensation plus dehydroxylation during the reaction of flavones and hydrazine. Eur J Org Chem. 2022. https://doi.org/10.1002/ejoc.202200455.
[83] Osella MI, Salazar MO, Gamarra MD, Moreno DM, Lambertucci F, Frances DE, Furlan RLE. Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors. RSC Med Chem. 2020;11:518-27. https://doi.org/10.1039/c9md00559e. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
