Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis

doi:10.1007/s13659-022-00331-6

摘要/Abstract

摘要： Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

关键词: Natural phenols, Structural derivatization, Common fragments, Total synthesis

Abstract: Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

Key words: Natural phenols, Structural derivatization, Common fragments, Total synthesis

Ding Lin, Senze Jiang, Ailian Zhang, Tong Wu, Yongchang Qian, Qingsong Shao. Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis[J]. 应用天然产物, 2022, 12(2): 8-8.

参考文献

1.Chen L, Teng H, Xie Z, Cao H, Cheang WS, Skalicka-Woniak K, Georgiev MI, Xiao J.Modifications of dietary flavonoids towards improved bioactivity:an update on structure-activity relationship.Crit Rev Food Sci Nutr.2018;58:513-27.
2.Zhou Y, Zheng J, Li Y, Xu DP, Li S, Chen YM, Li HB.Natural polyphenols for prevention and treatment of cancer.Nutrients.2016;8:515.
3.Mehmood A, Usman M, Patil P, Zhao L, Wang C.A review on management of cardiovascular diseases by olive polyphenols.Food Sci Nutr.2020;8:4639-55.
4.Caruana M, Vassallo N.Tea polyphenols in Parkinson's disease.Adv Exp Med Biol.2015;863:117-37.
5.Ho L, Pasinetti GM.Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding.Expert Rev Proteomics.2010;7:579-89.
6.Yu JS, Park M, Pang C, Rashan L, Jung WH, Kim KH.Antifungal phenols from Woodfordia uniflora collected in Oman.J Nat Prod.2020;83:2261-8.
7.Silva RFM, Pogacnik L.Polyphenols from food and natural products:neuroprotection and safety.Antioxidants.2020;9:61.
8.Mastinu A, Ribaudo G, Ongaro A, Bonini SA, Memo M, Gianoncelli A.Critical review on the chemical aspects of cannabidiol (cbd) and harmonization of computational bioactivity data.Curr Med Chem.2021;28:213-37.
9.Srinivasan K.Biological activities of red pepper (capsicum annuum) and its pungent principle capsaicin:a review.Crit Rev Food Sci Nutr.2016;56:1488-500.
10.Zhang Y, Qin L, Xie J, Li J, Wang C.Eupatilin prevents behavioral deficits and dopaminergic neuron degeneration in a Parkinson's disease mouse model.Life Sci.2020;253:117745.
11.Bi YL, Min M, Shen W, Liu Y.Genistein induced anticancer effects on pancreatic cancer cell lines involves mitochondrial apoptosis, G0/G1 cell cycle arrest and regulation of STAT3 signalling pathway.Phytomedicine.2018;39:10-6.
12.Wilson BAP, Thornburg CC, Henrich CJ, Grkovic T, O'Keefe BR.Creating and screening natural product libraries.Nat Prod Rep.2020;37:893-918.
13.Serrya MS, El-Sheakh AR, Makled MN.Evaluation of the therapeutic effects of mycophenolate mofetil targeting Nrf-2 and NLRP3 inflammasome in acetic acid induced ulcerative colitis in rats.Life Sci.2021;271:119154.
14.Gao F, Huang G, Xiao J.Chalcone hybrids as potential anticancer agents:current development, mechanism of action, and structureactivity relationship.Med Res Rev.2020;40:2049-84.
15.Piska K, Koczurkiewicz P, Bucki A, Wojcik-Pszczola K, Kolaczkowski M, Pekala E.Metabolic carbonyl reduction of anthracyclines-role in cardiotoxicity and cancer resistance.Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents.Invest New Drugs.2017;35:375-85.
16.Grisoni F, Merk D, Consonni V, Hiss JA, Tagliabue SG, Todeschini R, Schneider G.Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity.Commun Chem.2018;1:44.
17.Wang S, Dong G, Sheng C.Structural simplification of natural products.Chem Rev.2019;119:4180-220.
18.Guo Z.The modification of natural products for medical use.Acta Pharm Sin B.2017;7:119-36.
19.Liu R, Li X, Lam KS.Combinatorial chemistry in drug discovery.Curr Opin Chem Biol.2017;38:117-26.
20.Berthet J, Agouridas L, Chen S, Allouchi H, Melnyk P, Champagne B, Delbaere S.Synthesis and switching properties of new derivatives of azoresveratrol.Dyes Pigments.2019;171:107666.
21.Zacharias NM, Ornelas A, Lee J, Hu J, Davis JS, Uddin N, Pudakalakatti S, Menter DG, Karam JA, Wood CG, et al.Real-time interrogation of aspirin reactivity, biochemistry, and biodistribution by hyperpolarized magnetic resonance spectroscopy.Angew Chem Int Ed Engl.2019;58:4179-83.
22.Penalver P, Belmonte-Reche E, Adan N, Caro M, Mateos-Martin ML, Delgado M, Gonzalez-Rey E, Morales JC.Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases.Eur J Med Chem.2018;146:123-38.
23.Hassan F, Kawamoto M, Salikolimi K, Hashizume D, Hirose T, Ito Y.Onepot heterocyclic ring closure of 1,1'-bi-2-naphthol to 7H-dibenzo[c, g] carbazole.Tetrahedron Lett.2018;59:99-102.
24.Jaxel J, Amer H, Bacher M, Roller A, Guggenberger M, Zwirchmayr NS, Hansmann C, Liebner F.Facile synthesis of 1-butylamino-and 1,4-bis(butylamino)-2-alkyl-9,10-anthraquinone dyes for improved supercritical carbon dioxide dyeing.Dyes Pigments.2020;173:107991.
25.Labadie SS, Li J, Blake RA, Chang JH, Goodacre S, Hartman SJ, Liang W, Kiefer JR, Kleinheinz T, Lai T.Discovery of a C-8 hydroxychromene as a potent degrader of estrogen receptor alpha with improved rat oral exposure over GDC-0927.Bioorg Med Chem Lett.2019;29:2090-3.
26.Yu J, Zhang P, Wu J, Shang Z.Metal-free C-N bond-forming reaction:straightforward synthesis of anilines, through cleavage of aryl C-O bond and amide C-N bond.Tetrahedron Lett.2013;54:3167-70.
27.Crosby IT, Shin JK, Capuano B.The application of the schmidt reaction and beckmann rearrangement to the synthesis of bicyclic lactams:some mechanistic considerations.Aust J Chem.2010;63:211-26.
28.Beria I, Ballinari D, Bertrand JA, Borghi D, Bossi RT, Brasca MG, Cappella P, Caruso M, Ceccarelli W, Ciavolella A.Identification of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as a new class of orally and selective Polo-like kinase 1 inhibitors.J Med Chem.2010;53:3532-51.
29.Wu J, Yu J, Wang Y, Zhang P.Direct amination of phenols under metalfree conditions.Synlett.2013;24:1448-54.
30.Maguire CJ, Carlson GJ, Ford JW, Strecker TE, Hamel E, Trawick ML, Pinney KG.Synthesis and biological evaluation of structurally diverse alpha-conformationally restricted chalcones and related analogues.Medchemcomm.2019;10:1445-56.
31.Maltais R, Poirier D.Development of a gram-scale synthesis of pbrm, an irreversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1.Org Process Res Dev.2019;23:2323-35.
32.Boutard N, Bialas A, Sabiniarz A, Guzik P, Banaszak K, Biela A, Bien M, Buda A, Bugaj B, Cieluch E, et al.Discovery and structure-activity relationships of N-aryl 6-aminoquinoxalines as potent pfkfb3 kinase inhibitors.ChemMedChem.2019;14:169-81.
33.Liu Y, Liang Y, Jiang J, Qin Q, Wang L, Liu X.Design, synthesis and biological evaluation of 1,4-dihydroxyanthraquinone derivatives as anticancer agents.Bioorg Med Chem Lett.2019;29:1120-6.
34.Sagrera G, Bertucci A, Vazquez A, Seoane G.Synthesis and antifungal activities of natural and synthetic biflavonoids.Bioorg Med Chem.2011;19:3060-73.
35.Park J-Y, Kim S-W, Park H-J, Im W-B, Lee J-K, Yoon S-H.Synthesis and antioxidant effect of caffeic acid analogues bearing a carboxy and hydroxymethyl group.Bull Korean Chem Soc.2010;31:3860-3.
36.Tomanik M, Economou C, Frischling MC, Xue M, Marks VA, Mercado BQ, Herzon SB.Development of a convergent enantioselective synthetic route to (-)-myrocin g.J Org Chem.2020;85:8952-89.
37.Barontini M, Bernini R, Crisante F, Fabrizi G.Selective and efficient oxidative modifications of flavonoids with 2-iodoxybenzoic acid (IBX).Tetrahedron.2010;66:6047-53.
38.Koyani RD, Vazquez-Duhalt R.Enzymatic activation of the emerging drug resveratrol.Appl Biochem Biotechnol.2017;185:248-56.
39.Hong S, Liu S.Targeted acylation for all the hydroxyls of (+)-catechin and evaluation of their individual contribution to radical scavenging activity.Food Chem.2016;197:415-21.
40.Jiang Z-Y, Wang Y-G.A mild, efficient and selective deprotection of t-butyldimethylsilyl-protected phenols using cesium carbonate.Tetrahedron Lett.2003;44:3859-61.
41.Mashima K, Ohshima T, Iwasaki T, Maegawa Y, Hayashi Y.A simple, general, and highly chemoselective acetylation of alcohols using ethyl acetate as the acetyl donor catalyzed by a tetranuclear zinc cluster.Synlett.2009;2009:1659-63.
42.Miyazawa T, Yamamoto M, Danjo H.Selective acylation of the phenolic hydroxyl of (hydroxyalkyl)phenols by using vinyl carboxylates as acyl donors in the presence of rubidium fluoride.Monatsh Chem Chem Mon.2013;144:1351-4.
43.Liu HX, Dang YQ, Yuan YF, Xu ZF, Qiu SX, Tan HB.Diacyl disulfide:a reagent for chemoselective acylation of phenols enabled by 4-(N, N-dimethylamino)pyridine catalysis.Org Lett.2016;18:5584-7.
44.V R.K., A O.J.Partial methylation of quercetin:direct synthesis of tamarixetin, ombuin and ayanin.J Heterocycl Chem.1976; 13:1293-1295.
45.Jurd L.Plant polyphenols.V.Selective alkylation of the 7-hydroxyl group in polyhydroxyflavones.J Am Chem Soc.1958;80:5531-6.
46.Jurd L.The selective alkylation of polyphenols.II.Methylation of 7-, 4'-, and 3'-hydroxyl groups in flavonols.J Org Chem.1962;27:1294-7.
47.Li NG, Shi ZH, Tang YP, Yang JP, Duan JA.An efficient partial synthesis of 4'-O-methylquercetin via regioselective protection and alkylation of quercetin.Beilstein J Org Chem.2009;5:60.
48.Grynkiewicz G, Zegrocka-Stendel O, Pucko W, Ramza J, Kościelecka A, Kołodziejski W, Woźniak K.X-ray and 13C CP MAS investigations of structure of two genistein derivatives.J Mol Struct.2004;694:121-9.
49.Szeja W, Puchałka J, Świerk P, Hendrich AB, Grynkiewicz G.Selective alkylation of genistein and daidzein.Chem Biol Interface.2013;3:95-106.
50.Dai JL, Shao NQ, Zhang J, Jia RP, Wang DH.Cu(II)-catalyzed ortho-selective aminomethylation of phenols.J Am Chem Soc.2017;139:12390-3.
51.Shao NQ, Yao ZL, Wang DH.Cu(II)-catalyzed ortho-selective amination of simple phenols with o-benzoylhydroxylamines.Isr J Chem.2020;60:429-32.
52.Qian X, Han J, Wang L.Copper-catalyzed selective ortho-arylations of 2-naphthol and phenol derivatives with diaryliodonium salts.Tetrahedron Lett.2016;57:607-10.
53.Xiong X, Yeung Y-Y.Ammonium salt-catalyzed highly practical orthoselective monohalogenation and phenylselenation of phenols:scope and applications.ACS Catal.2018;8:4033-43.
54.Ackermann L.Carboxylate-assisted ruthenium-catalyzed alkyne annulations by C-H/Het-H bond functionalizations.Acc Chem Res.2014;47:281-95.
55.Reddy MC, Jeganmohan M.Ruthenium-catalyzed selective aerobic oxidativeortho-alkenylation of substituted phenols with alkenes through C-H bond activation.Eur J Org Chem.2013;2013:1150-7.
56.Kong ZL, Tzeng SC, Liu YC.Cytotoxic neolignans:an SAR study.Bioorg Med Chem Lett.2005;15:163-6.
57.Fang Y-T, Lin C-N, Wu H-T, Lee Y-J.Total synthesis of (±)-glyflavanone by a rigid quaternary ammonium salt.J Chin Chem Soc.2007;54:817-22.
58.Joshi BP, Sharma A, Sinha AK.Ultrasound-assisted convenient synthesis of hypolipidemic active natural methoxylated (E)-arylalkenes and arylalkanones.Tetrahedron.2005;61:3075-80.
59.Hassam M, Taher A, Arnott GE, Green IR, van Otterlo WA.Isomerization of allylbenzenes.Chem Rev.2015;115:5462-569.
60.Yadav Y, Owens EA, Sharma V, Aneja R, Henary M.Synthesis and evaluation of antiproliferative activity of a novel series of hydroxychavicol analogs.Eur J Med Chem.2014;75:1-10.
61.Freire RS, Morais SM, Catunda-Junior FE, Pinheiro DC.Synthesis and antioxidant, anti-inflammatory and gastroprotector activities of anethole and related compounds.Bioorg Med Chem.2005;13:4353-8.
62.Taferner B, Schuehly W, Huefner A, Baburin I, Wiesner K, Ecker GF, Hering S.Modulation of GABAA-receptors by honokiol and derivatives:subtype selectivity and structure-activity relationship.J Med Chem.2011;54:5349-61.
63.Saikia I, Borah AJ, Phukan P.Use of bromine and bromo-organic compounds in organic synthesis.Chem Rev.2016;116:6837-7042.
64.Das B, Venkateswarlu K, Damodar K, Suneel K.Ammonium acetate catalyzed improved method for the regioselective conversion of olefins into halohydrins and haloethers at room temperature.J Mol Catal A:Chem.2007;269:17-21.
65.Galli M, Fletcher CJ, Del Pozo M, Goldup SM.Scalable anti-Markovnikov hydrobromination of aliphatic and aromatic olefins.Org Biomol Chem.2016;14:5622-6.
66.Maxwell AC, Flanagan SP, Goddard R, Guiry PJ.Rhodium-catalysed hydroboration employing new Quinazolinap ligands:an investigation into electronic effects.Tetrahedron Asymmetry.2010;21:1458-73.
67.Connolly DJ, Lacey PM, McCarthy M, Saunders CP, Carroll A-M, Goddard R, Guiry PJ.Preparation and resolution of a modular class of axially chiral quinazoline-containing ligands and their application in asymmetric rhodium-catalyzed olefin hydroboration.J Org Chem.2004;69:6572-89.
68.McCarthy M, Guiry PJ, Hooper MW.Enantioselective hydroboration of olefins catalysed by cationic rhodium complexes of 2-phenylquinazolin-4-yl-2-(diphenylphosphino)naphthalene.Chem Commun.2000.https://doi.org/10.1039/b0040 14m.
69.Deng CM, Ma YF, Wen YM.Transition-metal-free borylation of alkynes and alkenes.ChemistrySelect.2018;3:1202-4.
70.Toribatake K, Nishiyama H.Asymmetric diboration of terminal alkenes with a rhodium catalyst and subsequent oxidation:enantioselective synthesis of optically active 1,2-diols.Angew Chem Int Ed Engl.2013;52:11011-5.
71.Coombs JR, Haeffner F, Kliman LT, Morken JP.Scope and mechanism of the Pt-catalyzed enantioselective diboration of monosubstituted alkenes.J Am Chem Soc.2013;135:11222-31.
72.Wang A, Jiang H.Palladium-catalyzed direct oxidation of alkenes with molecular oxygen:general and practical methods for the preparation of 1,2-diols, aldehydes, and ketones.J Org Chem.2010;75:2321-6.
73.Reddy CR, Rao NN, Srikanth B.Total synthesis of a diarylheptanoid, rhoiptelol b.Eur J Org Chem.2010;2010:345-51.
74.Lin D, Yi Y-J, Xiao M-W, Chen J, Ye J, Hu A-X, Lian W-W, Liu A-L, Du G-H.Design, synthesis and biological evaluation of honokiol derivatives as influenza neuraminidase inhibitors.J Asian Nat Prod Res.2019;21:1052-67.
75.Chen S, Zeng G, Li Y, He B, Liu R, Zhang S.Epoxide ring-opening reaction promoted by ionic liquid reactivity:interplay of experimental and theoretical studies.Catal Sci Technol.2019;9:5567-71.
76.Brunelli NA, Long W, Venkatasubbaiah K, Jones CW.Catalytic regioselective epoxide ring opening with phenol using homogeneous and supported analogues of dimethylaminopyridine.Top Catal.2012;55:432-8.
77.Telvekar VN, Patel DJ, Mishra SJ.Oxidative cleavage of epoxides using aqueous sodium paraperiodate.Synth Commun.2008;39:311-5.
78.Binder CM, Dixon DD, Almaraz E, Tius MA, Singaram B.A simple procedure for c-c bond cleavage of aromatic and aliphatic epoxides with aqueous sodium periodate under ambient conditions.Tetrahedron Lett.2008;49:2764-7.
79.Lin D, Wang L, Yan Z, Ye J, Hu A, Liao H, Liu J, Peng J.Semi-synthesis, structural modification and biological evaluation of 5-arylbenzofuran neolignans.RSC Adv.2018;8:34331-42.
80.Gieuw MH, Ke Z, Yeung YY.Lewis base-promoted ring-opening 1,3-dioxygenation of unactivated cyclopropanes using a hypervalent iodine reagent.Angew Chem Int Ed Engl.2018;57:3782-6.
81.Khan FA, Hussain MA.Total synthesis of (±)-cassumunins a-c and curcumin analogues.Synthesis.2020;52:1561-75.
82.Mitsudome T, Umetani T, Nosaka N, Mori K, Mizugaki T, Ebitani K, Kaneda K.Convenient and efficient Pd-catalyzed regioselective oxyfunctionalization of terminal olefins by using molecular oxygen as sole reoxidant.Angew Chem Int Ed Engl.2006;45:481-5.
83.Roshchin AI, Kel'chevski SM, Bumagin NA.Synthesis of benzofurans via Pd2+-catalyzed oxidative cyclization of 2-allylphenols.J Organomet Chem.1998;560:163-7.
84.Coulombel L, Duñach E.Triflic acid-catalysed cyclisation of unsaturated alcohols.Green Chem.2004;6:499-501.
85.Lin D, Yan Z, Chen A, Ye J, Hu A, Liu J, Peng J, Wu X.Anti-proliferative activity and structure-activity relationship of honokiol derivatives.Bioorg Med Chem.2019;27:3729-34.
86.Qunshan D, Yan Z, Zhenhua S, Chuanjun S, Junbiao C.Synthesis of a regioisomer of β-lapachone and analogs as potent antitumor agents.Helv Chim Acta.2015;98:128-34.
87.Yagunov SE, Khol′shin SV, Kandalintseva NV, Prosenko AE.Synthesis and antioxidant activity of 5-hydroxycoumarans, 6-hydroxychromanes and sulfur-containing derivatives on their base.Russ Chem Bull.2013;62:1395-400.
88.Vemula SR, Kumar D, Cook GR.Palladium-catalyzed allylic amidation with N-heterocycles via sp3 C-H oxidation.ACS Catal.2016;6:5295-301.
89.Pattillo CC, Strambeanu II, Calleja P, Vermeulen NA, Mizuno T, White MC.Aerobic linear allylic C-H amination:overcoming benzoquinone inhibition.J Am Chem Soc.2016;138:1265-72.
90.Ma R, White MC.C-H to C-N cross-coupling of sulfonamides with olefins.J Am Chem Soc.2018;140:3202-5.
91.Liu G, Yin G, Wu L.Palladium-catalyzed intermolecular aerobic oxidative amination of terminal alkenes:efficient synthesis of linear allylamine derivatives.Angew Chem.2008;120:4811-4.
92.Burman JS, Harris RJ, Farr CMB, Bacsa J, Blakey SB.Rh(III) and Ir(III)Cp* complexes provide complementary regioselectivity profiles in intermolecular allylic C-H amidation reactions.ACS Catal.2019;9:5474-9.
93.Knecht T, Mondal S, Ye JH, Das M, Glorius F.Intermolecular, branchselective, and redox-neutral Cp*Ir(III)-catalyzed allylic C-H amidation.Angew Chem Int Ed Engl.2019;58:7117-21.
94.Lei H, Rovis T.Ir-catalyzed intermolecular branch-selective allylic C-H amidation of unactivated terminal olefins.J Am Chem Soc.2019;141:2268-73.
95.Kazerouni AM, Nelson TAF, Chen SW, Sharp KR, Blakey SB.Regioselective Cp*Ir(III)-catalyzed allylic C-H sulfamidation of allylbenzene derivatives.J Org Chem.2019;84:13179-85.
96.Pandey G, Laha R.Visible-light-catalyzed direct benzylic C(sp(3))-H amination reaction by cross-dehydrogenative coupling.Angew Chem Int Ed Engl.2015;54:14875-9.
97.Sharma A, Hartwig JF.Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification.J Am Chem Soc.2013;135:17983-9.
98.Hussain N, Frensch G, Zhang J, Walsh PJ.Chemo-and regioselective C(sp(3))-H arylation of unactivated allylarenes by deprotonative crosscoupling.Angew Chem Int Ed Engl.2014;53:3693-7.
99.Lerchen A, Knecht T, Koy M, Ernst JB, Bergander K, Daniliuc CG, Glorius F.Non-directed cross-dehydrogenative (hetero)arylation of allylic C(sp3)-H bonds enabled by C-H Activation.Angew Chem Int Ed Engl.2018;57:15248-52.
100.Wang PS, Lin HC, Zhou XL, Gong LZ.Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination.Org Lett.2014;16:3332-5.
101.Brucelle F, Renaud P.Synthesis of a leucomitosane via a diastereoselective radical cascade.J Org Chem.2013;78:6245-52.
102.Li LL, Tao ZL, Han ZY, Gong LZ.Double chiral induction enables a stereoselective carbonyl allylation with simple alkenes under the sequential catalysis of palladium complex and chiral phosphoric acid.Org Lett.2017;19:102-5.
103.Tao ZL, Li XH, Han ZY, Gong LZ.Diastereoselective carbonyl allylation with simple olefins enabled by palladium complex-catalyzed C-H oxidative borylation.J Am Chem Soc.2015;137:4054-7.
104.Hemelaere R, Carreaux F, Carboni B.Cross-metathesis/isomerization/allylboration sequence for a diastereoselective synthesis of antihomoallylic alcohols from allylbenzene derivatives and aldehydes.Chemistry (Easton).2014;20:14518-23.
105.Schwarz JL, Schafers F, Tlahuext-Aca A, Luckemeier L, Glorius F.Diastereoselective allylation of aldehydes by dual photoredox and chromium catalysis.J Am Chem Soc.2018;140:12705-9.
106.Jalab M, Critchley ME, Taylor CM, Lawrence CL, Smith RB.1,8-Substituted anthraquinones, anthrones and bianthrones as potential nonazole leads against fungal infections.Bioorg Chem.2019;91:103151.
107.Goto H, Terao Y, Akai S.Synthesis of various kinds of isoflavones, isoflavanes, and biphenylketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities.Chem Pharm Bull (Tokyo).2009;54:346-60.
108.Abdo NYM, Samir EM, Mohareb RM.Synthesis and evaluation of novel 4H-pyrazole and thiophene derivatives derived from chalcone as potential anti-proliferative agents, Pim-1 kinase inhibitors, and PAINS.J Heterocycl Chem.2020;57:1993-2009.
109.Saito Y, Goto M, Nakagawa-Goto K.Total synthesis of antiproliferative parvifloron F.Org Lett.2018;20:628-31.
110.Gribble GW, Leese RM, Evans BE.Reactions of sodium borohydride in acidic media, iv.Reduction of diarylmethanols and triarylmethanols in trifluoroacetic acid.Cheminform.1977;8:172-6.
111.Fonovic UP, Knez D, Hrast M, Zidar N, Proj M, Gobec S, Kos J.Structureactivity relationships of triazole-benzodioxine inhibitors of cathepsin X.Eur J Med Chem.2020;193:112218.
112.Mikami S, Sasaki S, Asano Y, Ujikawa O, Fukumoto S, Nakashima K, Oki H, Kamiguchi N, Imada H, Iwashita H, et al.Discovery of an orally bioavailable, brain-penetrating, in vivo active phosphodiesterase 2a inhibitor lead series for the treatment of cognitive disorders.J Med Chem.2017;60:7658-76.
113.Jiang L, Yin R, Wang X, Dai J, Li J, Jiang T, Yu R.Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90.Eur J Med Chem.2017;135:24-33.
114.Zhu X, Zhou X, Zhang W.One-pot reductive amination of araldehydes by aniline using borohydride with CeCl₃·7H₂O as catalyst.J Chem Res.2015;39:390-3.
115.Monaldi D, Rotili D, Lancelot J, Marek M, Wossner N, Lucidi A, Tomaselli D, Ramos-Morales E, Romier C, Pierce RJ, et al.Structure-reactivity relationships on substrates and inhibitors of the lysine deacylase sirtuin 2 from schistosoma mansoni (smsirt2).J Med Chem.2019;62:8733-59.
116.Randino R, Cini E, D'Ursi AM, Novellino E, Rodriquez M.Facile Baeyer-Villiger oxidation of cyclic ketones:conventional versus microwaveassisted approach.Tetrahedron Lett.2015;56:5723-6.
117.Kumar N, Sharma CS, Ranawat MS, Singh HP, Chauhan LS, Dashora N.Synthesis, analgesic and anti-inflammatory activities of novel mannich bases of benzimidazoles.J Pharm Invest.2014;45:65-71.
118.Lu LP, Suo FZ, Feng YL, Song LL, Li Y, Li YJ, Wang KT.Synthesis and biological evaluation of vanadium complexes as novel anti-tumor agents.Eur J Med Chem.2019;176:1-10.
119.Hussain MK, Ansari MI, Yadav N, Gupta PK, Gupta AK, Saxena R, Fatima I, Manohar M, Kushwaha P, Khedgikar V, et al.Design and synthesis of ERα/ERβ selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents.RSC Adv.2014;4:8828-45.
120.Ducki S, Rennison D, Woo M, Kendall A, Chabert JF, McGown AT, Lawrence NJ.Combretastatin-like chalcones as inhibitors of microtubule polymerization.Part 1:synthesis and biological evaluation of antivascular activity.Bioorg Med Chem.2009;17:7698-710.
121.Huang JK, Shia KS.Development of a cross-conjugated vinylogous[4+2] anionic annulation and application to the total synthesis of natural antibiotic (+/-)-ABX.Angew Chem Int Ed Engl.2020;59:6540-5.
122.Pan G-F, Zhu X-Q, Guo R-L, Gao Y-R, Wang Y-Q.Synthesis of enones and enals via dehydrogenation of saturated ketones and aldehydes.Adv Synth Catal.2018;360:4774-83.
123.Ferreira JRM, Nunes da Silva R, Rocha J, Silva AMS, Guieu S.1,2,4-Triphenylpyrroles:synthesis, structure and luminescence properties.Synlett.2020;31:632-4.
124.Gupta RA, Kaskhedikar SG.Synthesis, antitubercular activity, and QSAR analysis of substituted nitroaryl analogs:chalcone, pyrazole, isoxazole, and pyrimidines.Med Chem Res.2012;22:3863-80.
125.Xu Z, Guo J, Yang Y, Zhang M, Ba M, Li Z, Cao Y, He R, Yu M, Zhou H, et al.2,4,5-Trisubstituted thiazole derivatives as HIV-1 NNRTIs effective on both wild-type and mutant HIV-1 reverse transcriptase:optimization of the substitution of positions 4 and 5.Eur J Med Chem.2016;123:309-16.
126.Evans RW, Zbieg JR, Zhu S, Li W, MacMillan DW.Simple catalytic mechanism for the direct coupling of alpha-carbonyls with functionalized amines:a one-step synthesis of Plavix.J Am Chem Soc.2013;135:16074-7.
127.Jiang Q, Xu B, Zhao A, Jia J, Liu T, Guo C.Transition-metal-free oxidative alpha-C-H amination of ketones via a radical mechanism:mild synthesis of alpha-amino ketones.J Org Chem.2014;79:8750-6.
128.Liang YF, Wu K, Song S, Li X, Huang X, Jiao N.I2-or NBS-catalyzed highly efficient alpha-hydroxylation of ketones with dimethyl sulfoxide.Org Lett.2015;17:876-9.
129.Li H-L, An X-L, Ge L-S, Luo X, Deng W-P.Catalytic α-hydroxylation of ketones under CuBr 2 or HBr/DMSO systems.Tetrahedron.2015;71:3247-52.
130.Hamed OA, El-Qisairi A, Qaseer H, Hamed EM, Henry PM, Becker DP.Asymmetric α-hydroxy ketone synthesis by direct ketone oxidation using a bimetallic palladium(II) complex.Tetrahedron Lett.2012;53:2699-701.
131.Huang X, Liang X, Yuan J, Ni Z, Zhou Y, Pan Y.Aerobic copper catalyzed α-oxyacylation of ketones with carboxylic acids.Org Chem Front.2017;4:163-9.
132.Guo S, Yu JT, Dai Q, Yang H, Cheng J.The Bu4NI-catalyzed alfa-acyloxylation of ketones with benzylic alcohols.Chem Commun (Camb).2014;50:6240-2.
133.Zhu C, Zhang Y, Zhao H, Huang S, Zhang M, Su W.Sodium iodidecatalyzed direct α-alkoxylation of ketones with alcoholsviaoxidation of α-iodo ketone intermediates.Adv Synth Catal.2015;357:331-8.
134.Wong T, Narayanan S, Brown DP, Chen ZS.Synthesis and cytotoxicity studies of stilbene long-chain fatty acid conjugates.J Nat Prod.2020;83:1563-70.
135.Lu C, Guo Y, Li J, Yao M, Liao Q, Xie Z, Li X.Design, synthesis, and evaluation of resveratrol derivatives as Ass((1)-(4)(2)) aggregation inhibitors, antioxidants, and neuroprotective agents.Bioorg Med Chem Lett.2012;22:7683-7.
136.Akcok I, Cagir A.Synthesis of stilbene-fused 2'-hydroxychalcones and flavanones.Bioorg Chem.2010;38:139-43.
137.Floresta G, Cilibrizzi A, Abbate V, Spampinato A, Zagni C, Rescifina A.3D-QSAR assisted identification of FABP4 inhibitors:an effective scaffold hopping analysis/QSAR evaluation.Bioorg Chem.2019;84:276-84.
138.Kindt S, Wicht K, Heinrich MR.Thermally induced carbohydroxylation of styrenes with aryldiazonium salts.Angew Chem Int Ed Engl.2016;55:8744-7.
139.Wang T, Hu Y, Zhang S.A novel and efficient method for the olefination of carbonyl compounds with Grignard reagents in the presence of diethyl phosphite.Org Biomol Chem.2010;8:2312-5.
140.Fang Y, Xia W, Cheng B, Hua P, Zhou H, Gu Q, Xu J.Design, synthesis, and biological evaluation of compounds with a new scaffold as anti-neuroinflammatory agents for the treatment of Alzheimer's disease.Eur J Med Chem.2018;149:129-38.
141.Thompson CM, Orellana MD, Lloyd SE, Wu W.Stereospecific synthesis of cis-stilbenes from benzaldehydes and phenylacetic acids via sequential Perkin condensation and decarboxylation.Tetrahedron Lett.2016;57:4866-8.
142.Li S-Y, Wang X-B, Kong L-Y.Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer's disease.Eur J Med Chem.2014;71:36-45.
143.Reinhardt CJ, Zhou EY, Jorgensen MD, Partipilo G, Chan J.A ratiometric acoustogenic probe for in vivo imaging of endogenous nitric oxide.J Am Chem Soc.2018;140:1011-8.
144.Zhao Y, Cao Y, Chen H, Zhuang F, Wu C, Yoon G, Zhu W, Su Y, Zheng S, Liu Z, et al.Synthesis, biological evaluation, and molecular docking study of novel allyl-retrochalcones as a new class of protein tyrosine phosphatase 1B inhibitors.Bioorg Med Chem.2019;27:963-77.
145.Liu J, Chen C, Wu F, Zhao L.Microwave-assisted synthesis and tyrosinase inhibitory activity of chalcone derivatives.Chem Biol Drug Des.2013;82:39-47.
146.Wen P, Tie W, Wang L, Lee M-H, Li X-D.Ultrasonic synthesis of 4,4'-dihydroxychalcone and its photochemical properties.Mater Chem Phys.2009;117:1-3.
147.Takao K, Yamashita M, Yashiro A, Sugita Y.Synthesis and biological evaluation of 3-benzylidene-4-chromanone derivatives as free radical scavengers and α-glucosidase inhibitors.Chem Pharm Bull (Tokyo).2016;64:1203-7.
148.Bin ZJIC.Synthesis of chalcone catalyzed by solid superbase.Ind Catal.2008;16:71-4.
149.Rakesh S, Sakthidharan CP, Sarojadevi M, Sundararajan PR.Monomer self assembly and organo-gelation as a route to fabricate cyanate ester resins and their nanocomposites with carbon nanotubes.Eur Polym J.2015;68:161-74.
150.Manickam M, Pichaimani P, Arumugam H, Muthukaruppan A.Synthesis of nontoxic pyrazolidine-based benzoxazine-coated cotton fabric for oil-water separation.Ind Eng Chem Res.2019;58:21419-30.
151.Karki R, Park C, Jun KY, Kadayat TM, Lee ES, Kwon Y.Synthesis and biological activity of 2,4-di-p-phenolyl-6-2-furanyl-pyridine as a potent topoisomerase II poison.Eur J Med Chem.2015;90:360-78.
152.Gaur R, Pathania AS, Malik FA, Bhakuni RS, Verma RK.Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.Eur J Med Chem.2016;122:232-46.
153.Liu C, Achtenhagen M, Szostak M.Chemoselective ketone synthesis by the addition of organometallics to N-acylazetidines.Org Lett.2016;18:2375-8.
154.Kumar A, Akula HK, Lakshman MK.Simple synthesis of amides and weinreb amides via use of pph3 or polymer-supported pph3 and iodine.Eur J Org Chem.2010.https://doi.org/10.1002/ejoc.200901420.
155.Crawford JJ, Henderson KW, Kerr WJ.Direct and efficient one-pot preparation of ketones from aldehydes using N-tert-butylphenylsulfinimidoyl chloride.Org Lett.2006;8:5073-6.
156.Cui Y, Li Y, Huang N, Xiong Y, Cao R, Meng L, Liu J, Feng Z.Structure based modification of chalcone analogue activates Nrf2 in the human retinal pigment epithelial cell line ARPE-19.Free Radic Biol Med.2020;148:52-9.
157.Firouzabadi H, Karimi B, Abbassi M.Efficient solvent-free oxidation of benzylic and aromatic allylic alcohols and biaryl acyloins by manganese dioxide and barium manganate.J Chem Res.1999.https://doi.org/10.1039/a806954i.
158.Salehi P, Firouzabadi H, Farrokhi A, Gholizadeh M.Solvent-free oxidations of alcohols, oximes, aldehydes and cyclic acetals by pyridinium chlorochromate.Synthesis.2001;15:2273-6.
159.Nishimura T, Onoue T, Ohe K, Uemura S.Palladium(II)-catalyzed oxidation of alcohols to aldehydes and ketones by molecular oxygen.J Org Chem.1999;64:6750-5.
160.Riemer D, Mandaviya B, Schilling W, Götz AC, Kühl T, Finger M, Das S.CO₂-catalyzed oxidation of benzylic and allylic alcohols with DMSO.ACS Catal.2018;8:3030-4.
161.Jagtap PR, Cisarova I, Jahn U.Bioinspired total synthesis of tetrahydrofuran lignans by tandem nucleophilic addition/redox isomerization/oxidative coupling and cycloetherification reactions as key steps.Org Biomol Chem.2018;16:750-5.
162.Shoola CO, DelMastro T, Wu R, Sowa JR.Asymmetric transfer hydrogenation of secondary allylic alcohols.Eur J Org Chem.2015;2015:1670-3.
163.Ibrahim JJ, Reddy CB, Zhang S, Yang Y.Ligand-free FeCl₂-catalyzed α-alkylation of ketones with alcohols.Asian J Org Chem.2019;8:1858-61.
164.Monserrat J-P, Tiwari KN, Quentin L, Pigeon P, Jaouen G, Vessières A, Chabot GG, Hillard EA.Ferrocenyl flavonoid-induced morphological modifications of endothelial cells and cytotoxicity against B16 murine melanoma cells.J Organomet Chem.2013;734:78-85.
165.Gutam M, Mokenapelli S, Yerrabelli JR, Banerjee S, Roy P, Chitneni PR.Synthesis and cytotoxicity of novel (E)-2-phenylchroman-4-one-O-((1-substituted-1H-1,2,3-triazol-4-yl)methyl) oxime derivatives.Synth Commun.2020;50:1883-91.
166.Imran S, Taha M, Ismail NH, Kashif SM, Rahim F, Jamil W, Wahab H, Khan KM.Synthesis, in vitro and docking studies of new flavone ethers as alpha-glucosidase inhibitors.Chem Biol Drug Des.2016;87:361-73.
167.Nayak BV, Ciftci-Yabanoglu S, Bhakat S, Timiri AK, Sinha BN, Ucar G, Soliman ME, Jayaprakash V.Monoamine oxidase inhibitory activity of 2-aryl-4H-chromen-4-ones.Bioorg Chem.2015;58:72-80.
168.Ramesh P, Reddy CS, Suresh BK, Reddy PM, Srinivasa RV, Parthasarathy T.Synthesis, characterization and molecular docking studies of novel 2-amino 3-cyano pyrano[2,3H]chrysin derivatives as potential antimicrobial agents.Med Chem Res.2015;24:3696-709.
169.Miyake H, Takizawa E, Sasaki M.Syntheses of flavones via the iodinemediated oxidative cyclization of 1,3-diphenylprop-2-en-1-ones.Bull Chem Soc Jpn.2003;76:835-6.
170.Patil AM, Kamble DA, Lokhande PD.Iodine-mediated direct synthesis of 3-iodoflavones.Synth Commun.2018;48:1299-307.
171.Lahyani A, Trabelsi M.Ultrasonic-assisted synthesis of flavones by oxidative cyclization of 2'-hydroxychalcones using iodine monochloride.Ultrason Sonochem.2016;31:626-30.
172.Kulkarni P, Kondhare D, Varala R, Zubaidha P.Cyclization of 2'-hydroxychalcones to flavones using ammonium iodide as an iodine source:an eco-friendly approach.J Serb Chem Soc.2013;78:909-16.
173.Vimal M, Pathak U, Halve AK.Water-mediated phosphorylative cyclodehydrogenation:an efficient preparation of flavones and flavanones.Synth Commun.2019;1-10.

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