Co-reporter:Gao-Feng Zha, Jing Leng, N. Darshini, T. Shubhavathi, H.K. Vivek, Abdullah M. Asiri, Hadi M. Marwani, K.P. Rakesh, N. Mallesha, Hua-Li Qin
Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 14(Issue 14) pp:
Publication Date(Web):15 July 2017
DOI:10.1016/j.bmcl.2017.05.032
A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole.A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring. The electron donating (OH and OCH3) groups presented in the analogues, increase the antibacterial activity (except compound 12), interestingly, while the electron withdrawing (Cl, NO2, F and Br) groups increase the antifungal activity (except compound 19 and 20). In addition, analogues containing thiophene (28) and indole (30) showed good antimicrobial activities. Whereas, aliphatic analogues (24–26) shown no activities in both bacterial and fungal stains even in high concentrations (100 µg/mL). Molecular docking studies were performed for all the synthesized compounds of which compounds 11, 19 and 20 showed the highest glide G-score.Download high-res image (197KB)Download full-size image
Co-reporter:Gao-Feng Zha, Hua-Li Qin, Bahaa G.M. Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H. Abdelazeem, Syed Nasir Abbas Bukhari
European Journal of Medicinal Chemistry 2017 Volume 135(Volume 135) pp:
Publication Date(Web):28 July 2017
DOI:10.1016/j.ejmech.2017.04.025
•New 34 ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes were synthesized.•All new compounds were evaluated for their effects on different types of cancer cell lines.•For most active compounds detailed mechanistic anticancer studies were performed.•New derivatives 5 and 7 (b,e,f) exhibited a dual role as anticancer as well as MDR reversal agents.The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation. A strong SAR was provided by the antiproliferative activity. The mechanistic effects of most active antiproliferative compounds on tubulin polymerization, EGFR TK kinases, KAF and BRAFV600E were investigated, followed by in vitro investigation of reversal of efflux-based resistance developed by cancer cells. EGFR was strongly inhibited by two oximes 7e and 8o. Out of all linkers including positive control, 1-isopropyl-piperidin-4-one linker-bearing compounds showed best inhibition of FAK. The strongest inhibitory activity of BRAFV600E was showed by compound 5e with an IC50 of 0.7 μM. Analogs such as 5 and 7 (b,e,f) exhibited a dual role as anticancer as well as MDR reversal agents. For understanding the target protein integrations with new compounds, molecular docking studies were also carried out.Download high-res image (364KB)Download full-size image
Co-reporter:Gao-Feng Zha;Grant A. L. Bare;Jing Leng;Zhen-Peng Shang;Zhixiong Luo;Hua-Li Qin
Advanced Synthesis & Catalysis 2017 Volume 359(Issue 18) pp:3237-3242
Publication Date(Web):2017/09/18
DOI:10.1002/adsc.201700688
AbstractA practical oxidative Heck reaction between organoboronic acids and ethenesulfonyl fluoride (ESF) is developed. Aryl- and heteroaryl-boronic acids react efficiently and stereoselectively with ESF in the presence of a catalytic amount of Pd(OAc)2 and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) or AgNO3 in AcOH to afford the corresponding E-isomer of β-arylethenesulfonyl fluoride products. The utility of this reaction is exemplified by an expanded scope of 47 examples including N-, O-, and S-containing heteroaromatics, demonstrating chemoselectivity over aryliodides, and gram-scale operation without the requirement for strict anhydrous or oxygen-free conditions. Furthermore, this procedure discriminates against the formation of arylboronic acids homo-coupling byproducts. In addition, the preparation of the first aryl vinylsulfonate polymer, a material with functionalizable Michael acceptor sites, from a starting arylboronic acid is described.
Co-reporter:Xing Chen;Gao-Feng Zha;Grant A. L. Bare;Jing Leng;Shi-Meng Wang;Hua-Li Qin
Advanced Synthesis & Catalysis 2017 Volume 359(Issue 18) pp:3254-3260
Publication Date(Web):2017/09/18
DOI:10.1002/adsc.201700887
Abstract(E)-2-(hetero)arylethenesulfonyl fluorides and (E,E)-1,3-dienylsulfonyl fluorides are bis-electrophiles and rare members of the sulfonyl fluoride family with limited information being known of their reactivity and synthetic utility. The direct annulation reaction of these 2-substituted ethenesulfonyl fluorides with medicinally important enolizable pyrazolones and 1,3-dicarbonyl compounds utilizing catalytic DBU in DCM under mild conditions leads to over 50 structurally diverse δ-sultone fused heterocycles with a pyrazolone ring or a cyclic enone, respectively, in good to excellent yield. The double bond at the 1-position adjacent to the sulfonyl fluoride group in 1,3-dienylsulfonyl fluoride is the chemoselective site of reactivity but is less reactive than the double bond of arylethenesulfonyl fluoride. High turnover and robustness of construction for these fused heterocycles, including the novel fused pyrazolone δ-sultone heterocycle series, may make compounds like these attractive to drug discovery, development and material science.
Co-reporter:Xiao-Yan Wang, Jing Leng, Shi-Meng Wang, Abdullah M. Asiri, Hadi M. Marwani, Hua-Li Qin
Tetrahedron Letters 2017 Volume 58, Issue 24(Issue 24) pp:
Publication Date(Web):14 June 2017
DOI:10.1016/j.tetlet.2017.04.070
•A one-pot mild process for direct hydrodeoxygenation of phenols to arenes.•This method displays wide scope compatibility and functional groups tolerability.•This protocol is applicable for hydrodeoxygenation of complicated molecules and multi-phenolic compounds.A practical one-pot process for hydrodeoxygenation (HDO) of phenolic derivatives to their corresponding arenes was developed. This method provided a facile route to upgrading bio-oil. The substrate scope of this protocol was wide, complicated and multi-phenolic compounds were also smoothly hydrodeoxygenated to their corresponding arenes.A facile and mild process for direct converting phenols to arenes with a wide scope compatibility and functional groups tolerability.Download high-res image (85KB)Download full-size image
Co-reporter:K. P. Rakesh;C. S. Shantharam;M. B. Sridhara;H. M. Manukumar;Hua-Li Qin
MedChemComm (2010-Present) 2017 vol. 8(Issue 11) pp:2023-2039
Publication Date(Web):2017/11/16
DOI:10.1039/C7MD00449D
The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation agents and so on. This review examines the state of the art in medicinal chemistry as it relates to the comprehensive and general summary of the different benzisoxazole analogs, their use as starting building blocks of multifarious architectures on scales sufficient to drive human drug trials. The number of reports describing benzisoxazole-containing highly active compounds leads to the expectation that this scaffold will further emerge as a potential candidate in the field of drug discovery.
Co-reporter:Shi-Meng Wang;Gao-Feng Zha;K. P. Rakesh;N. Darshini;T. Shubhavathi;H. K. Vivek;N. Mallesha;Hua-Li Qin
MedChemComm (2010-Present) 2017 vol. 8(Issue 6) pp:1173-1189
Publication Date(Web):2017/06/21
DOI:10.1039/C7MD00111H
A series of new benzo[d]thiazole-hydrazones were synthesized and characterized by analytical and spectroscopic techniques. All the compounds were screened for their in vitro inhibition of H+/K+ ATPase and anti-inflammatory effects. The results revealed that compounds 6–8, 13–15, 18–20, 22, 23 and 27–30 displayed excellent inhibitory activity against H+/K+ ATPase, and their IC50 values were lower than those of the standard compound omeprazole. Compounds 2–5, 9–12, 28 and 30 exhibited better anti-inflammatory activity in comparison to the standard compound indomethacin. Studies of the structure–activity relationship (SAR) showed that electron-donating groups (OH and OCH3) favored inhibitory activity against H+/K+ ATPase, whereas electron-withdrawing groups (F, Cl, Br and NO2) favored anti-inflammatory activity, and derivatives with both electron-donating (OH and OCH3) and electron-withdrawing (Br) groups (16–18) displayed reasonable activity, whereas aliphatic analogues (24–26) exhibited less activity and heterocyclic analogues (27–30) displayed moderate activity in both biological studies. Molecular docking studies were performed for all the synthesized compounds, among which compounds 19 and 20 exhibited the highest docking scores for inhibitory activity against H+/K+ ATPase, whereas compounds 10 and 12 displayed the highest docking scores for anti-inflammatory activity.
Co-reporter:Xing Chen;Jing Leng;K. P. Rakesh;N. Darshini;T. Shubhavathi;H. K. Vivek;N. Mallesha;Hua-Li Qin
MedChemComm (2010-Present) 2017 vol. 8(Issue 8) pp:1706-1719
Publication Date(Web):2017/08/16
DOI:10.1039/C7MD00209B
A series of novel xanthone conjugated amino acids were synthesised and characterised by analytical and spectroscopic methods. All the synthesized analogues (2–23) were screened for their in vitro antimicrobial and anti-inflammatory activities. Compounds 7, 8, 9, 12, 18, 19, 20, 21 and 23 showed excellent antimicrobial activities compared to antibacterial and antifungal reference drugs gentamicin and bavistin, respectively. Compounds 7–12 and 18–23 showed good anti-inflammatory activity compared to a standard drug, indomethacin. The preliminary structure–activity relationship revealed that tryptophan, tyrosine, phenylalanine, proline and cysteine conjugated compounds showed excellent antimicrobial and anti-inflammatory activities. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Molecular docking studies were performed for all the synthesised compounds, among which compounds 20, 21 and 23 showed the highest docking scores for antimicrobial activity while compounds 9, 20 and 22 showed the highest docking scores for anti-inflammatory activity. Different amino acids conjugated xanthone derivatives were synthesized and evaluated for their in vitro biological activities. The conjugation was found to play a major role in improving the biological activities of those compounds.
Co-reporter:Gao-Feng Zha;Hua-Li Qin;Eric Assen B. Kantchev
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 10) pp:2226-2233
Publication Date(Web):2017/03/08
DOI:10.1039/C6OB02651F
Atropisomeric biaryl disulfoxides contain two independent chiral elements. Previously, the (M,S,S)-diastereomer showed very high catalytic activity and selectivity in the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-enones whereas the (M,R,R) counterpart – none. Herein, DFT computations on the key transmetallation (turnover-determining) and carborhodation (enantioselectivity-determining) steps of the catalytic cycle show that the (M,S,S)-ligand gives rise to lower reaction barriers for these elementary steps. However, the barriers for the (M,R,R)-ligand are not sufficiently high to explain the lack of reactivity. Hence, this phenomenon is most likely due to the failure of catalyst formation from the ligand and the dimeric Rh precatalyst complex. The hitherto unknown (M,S,R)-ligand shows predicted enantioselectivity similar to the (M,S,S)-ligand as a consequence of lower reaction barriers associated with those isomers whose key features resemble the (M,S,S)-ligand.
Co-reporter:Syed Nasir Abbas Bukhari, Gajjela Bharath Kumar, Hrishikesh Mohan Revankar, Hua-Li Qin
Bioorganic Chemistry 2017 Volume 72(Volume 72) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.bioorg.2017.04.007
The combretastatins are isolated from South African tree combretum caffrum kuntze. The lead compound combretastatin A-4 has displayed remarkable cytotoxic effect in a wide variety of preclinical tumor models and inhibits tubulin polymerization by interacting at colchicine binding site of microtubule. However, the structural simplicity of C A-4 is favorable for synthesis of various derivatives projected to induce rapid and selective vascular shutdown in tumors. Majority of the molecules have shown excellent antiproliferative activity and are able to inhibit tubulin polymerization as well as possible mechanisms of action have been investigated. In this review article, the synthesis and structure-activity relationships of C A-4 and immense number of its synthetic derivatives with various modifications on the A, B-rings, bridge carbons and their anti mitotic activities are discussed.Download high-res image (104KB)Download full-size image
Co-reporter:Hrishikesh Mohan Revankar, Syed Nasir Abbas Bukhari, Gajjela Bharath Kumar, Hua-Li Qin
Bioorganic Chemistry 2017 Volume 71(Volume 71) pp:
Publication Date(Web):1 April 2017
DOI:10.1016/j.bioorg.2017.02.001
The discovery of COX enzymes has led to a better understanding of inflammation and its related biological pathways. Apart from being related to inflammation and pain, it has also been associated with cancer and neuropsychiatric diseases such as schizophrenia. Proverbially speaking, study of these enzymes has been crucial as they happen to “have fingers in many pies”. Non-steroidal anti-inflammatory drugs (NSAID) that act specifically as COX-2 inhibitors have been known for a while; however these are also associated with severe side effects such as cardiac problems. Several heterocylic molecules have been tested for their anti-inflammatory activity specifically as COX-inhibitors. Coumarins also known as benzopyrans are widely found in nature, and are routinely employed as herbal remedies since early days. Over 1300 coumarins have been identified, principally as secondary metabolites in green plants, fungi and bacteria. Recently the use of natural and synthetic coumarins has garnered a lot of attention for their anti-inflammatory activities. In this review we delve further into the study of natural and synthetic coumarins as COX-inhibitors. Although the study is still in its nascent stage, we believe there is scope for a lot of development.Download high-res image (67KB)Download full-size image
Co-reporter:Gao-Feng Zha, Jia-Bin Han, Xiao-Qian Hu, Hua-Li Qin, Wan-Yin Fang and Cheng-Pan Zhang
Chemical Communications 2016 vol. 52(Issue 47) pp:7458-7461
Publication Date(Web):21 Apr 2016
DOI:10.1039/C6CC03040H
Silver-mediated direct trifluoromethoxylation of α-diazo esters and ketosteroid was disclosed. The reactions of alkyl α-diazo arylacetates with AgOCF3 or CF3SO2OCF3/AgF at −30 to 10 °C under a N2 atmosphere provided α-trifluoromethoxyl arylacetates in up to 90% yield, while alkyl α-diazo vinylacetates reacting with CF3SO2OCF3/AgF or AgOCF3 afforded γ-trifluoromethoxyl α,β-unsaturated esters in up to 94% yield. The α-diazo ketosteroid was also trifluoromethoxylated under the standard reaction conditions. This protocol allows for an effective and convenient access to a large number of synthetic building blocks, which are promising in the development of new functional OCF3-molecules.
Co-reporter:Hua-Li Qin; Jing Leng; Cheng-Pan Zhang; Ibrahim Jantan; Muhammad Wahab Amjad; Muhammad Sher; Muhammad Naeem-ul-Hassan; Muhammad Ajaz Hussain;Syed Nasir Abbas Bukhari
Journal of Medicinal Chemistry 2016 Volume 59(Issue 7) pp:3549-3561
Publication Date(Web):March 24, 2016
DOI:10.1021/acs.jmedchem.6b00276
Sixty-nine novel α,β-unsaturated carbonyl based compounds, including cyclohexanone, tetralone, oxime, and oxime ether analogs, were synthesized. The antiproliferative activity determined by using seven different human cancer cell lines provided a structure–activity relationship. Compound 8ag exhibited high antiproliferative activity against Panc-1, PaCa-2, A-549, and PC-3 cell lines, with IC50 value of 0.02 μM, comparable to the positive control Erlotinib. The ten most active antiproliferative compounds were assessed for mechanistic effects on BRAFV600E, EGFR TK kinases, and tubulin polymerization, and were investigated in vitro to reverse efflux-mediated resistance developed by cancer cells. Compound 8af exhibited the most potent BRAFV600E inhibitory activity with an IC50 value of 0.9 μM. Oxime analog 7o displayed the most potent EGFR TK inhibitory activity with an IC50 of 0.07 μM, which was analogous to the positive control. Some analogs including 7f, 8af, and 8ag showed a dual role as anticancer and MDR reversal agents.
Co-reporter:Gao-Feng Zha, Cheng-Pan Zhang, Hua-Li Qin, Ibrahim Jantan, Muhammad Sher, Muhammad Wahab Amjad, Muhammad Ajaz Hussain, Zahid Hussain, Syed Nasir Abbas Bukhari
Bioorganic & Medicinal Chemistry 2016 Volume 24(Issue 10) pp:2352-2359
Publication Date(Web):15 May 2016
DOI:10.1016/j.bmc.2016.04.015
A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1–42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1–42 aggregation. The compound 3o exhibited best AChE (IC50 = 0.037 μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.The pharmacological evaluation of compounds comprises BuChE and AChE inhibition, amyloid β-induced cytotoxicity in PC12 cells and effects on self-induced Aβ aggregation.
Co-reporter:Zhen-Peng Shang, Gao-Feng Zha, Xiao-Qing Chen, Hua-Li Qin
Tetrahedron Letters 2016 Volume 57(Issue 42) pp:4680-4683
Publication Date(Web):19 October 2016
DOI:10.1016/j.tetlet.2016.09.008
•A visible-light-mediated aerobic oxidative dimerizative annulation of β-carbonylketones was developed.•This method allows the facile assembly of highly functionalized furans under mild conditions.•This protocol has the potentiality for both laboratory synthesis and industrial production.A green and convenient method for the synthesis of highly functionalized furans is developed through visible-light-mediated aerobic oxidative dimerizative annulation of β-carbonylketones. This protocol represents a novel and efficient way to construction of highly functionalized furans from basic starting materials under mild conditions.
Co-reporter:Xiao-Yan Wang, Zhen-Peng Shang, Gao-Feng Zha, Xiao-Qing Chen, Syed Nasir Abbas Bukhari, Hua-Li Qin
Tetrahedron Letters 2016 Volume 57(Issue 50) pp:5628-5631
Publication Date(Web):14 December 2016
DOI:10.1016/j.tetlet.2016.11.002
•A process of visible light promoted aerobic oxidative cleavage β-diketones was developed.•This method provides a mild and green option for the assemble of carboxylic acids.•The reaction was proceeded in a broad scope with excellent yield.A mild and highly efficient method for the preparation of carboxylic acids is developed through a visible-light-mediated aerobic oxidative cleavage of β-diketones. This process provides a potential general, practical and scalable protocol for both laboratory synthesis and industrial production of carboxylic acids in a green manner.A mild and highly efficient method for the preparation of carboxylic acids is developed through a visible-light-mediated aerobic oxidative cleavage of β-diketones. This process provides a general and practical protocol for both laboratory synthesis and industrial production of carboxylic acids in a green manner.
Co-reporter:Mei Shao, Zahid Hussain, Hnin Ei Thu, Shahzeb Khan, Haliza Katas, Tarek A. Ahmed, Minaketan Tripathy, Jing Leng, Hua-Li Qin, Syed Nasir Abbas Bukhari
Colloids and Surfaces B: Biointerfaces 2016 Volume 147() pp:475-491
Publication Date(Web):1 November 2016
DOI:10.1016/j.colsurfb.2016.08.027
•Lack of versatile choice results in escalation of prevalence of atopic diseases.•Reduced efficiency of conventional modalities demands newer therapies.•Nanocarrier-based formulations produced desired anti-dermatitis effects.•Therapeutic superiority of the nanocarrier-based therapies is proposed.Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.
Co-reporter:Kaicheng Zhu, Jian-Hong Hao, Cheng-Pan Zhang, Jiajun Zhang, Yiqing Feng and Hua-Li Qin
RSC Advances 2015 vol. 5(Issue 15) pp:11132-11135
Publication Date(Web):06 Jan 2015
DOI:10.1039/C4RA15765F
A highly efficient diversified methodology for preparation of benzimidazole, quinazolin-4(3H)-ones and 1,4-benzodiazepine-2,5-diones is established using a palladium-catalyzed transfer hydrogenation (CTH)/condensation cascade of o-nitroaniline and o-nitrobenzamides in a triethylamine–formic acid azeotropic mixture (2:5) under microwave irradiation.
Co-reporter:Shi-Meng Wang, Jia-Bin Han, Cheng-Pan Zhang, Hua-Li Qin
Tetrahedron Letters 2015 Volume 56(Issue 45) pp:6219-6222
Publication Date(Web):4 November 2015
DOI:10.1016/j.tetlet.2015.09.092
(E)-Bis(phosphonium)ethylenes were synthesized from aryl-, alkyl-, and arylalkylphosphines under solvent-free conditions using TfOCH2CF2H as reagent. The reaction allows for a convenient access to vinylenebis(trialkylphosphonium) salts in good to high yields.(E)-Bis(phosphonium)ethylenes were synthesized from aryl-, alkyl-, and arylalkylphosphines under solvent-free conditions using TfOCH2CF2H as reagent. The reaction allows for a convenient access to vinylenebis(trialkylphosphonium) salts in good to high yields.
Co-reporter:Shi-Meng Wang, Jia-Bin Han, Cheng-Pan Zhang, Hua-Li Qin, Ji-Chang Xiao
Tetrahedron 2015 Volume 71(Issue 42) pp:7949-7976
Publication Date(Web):21 October 2015
DOI:10.1016/j.tet.2015.06.056
Co-reporter: Hua-Li Qin;Xiao-Qing Chen;Zhen-Peng Shang; Eric Assen B. Kantchev
Chemistry - A European Journal 2015 Volume 21( Issue 7) pp:3079-3086
Publication Date(Web):
DOI:10.1002/chem.201405189
Abstract
Why are linear (E)-enones such challenging substrates in the Rh-catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to RhI π-complexed with the CC bond within the enantioselectivity-determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s-cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation-only substrate “probes”, one of which is capable of double asymmetric induction, and a recent computationally designed 1,5-diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three-pronged approach: 1) thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2) including dispersion interaction and long-range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3) full substrate and ligand modeling. Based on the results, a theory-enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.
Co-reporter:Hua-Li Qin, Jia-Bin Han, Jian-Hong Hao and Eric Assen B. Kantchev
Green Chemistry 2014 vol. 16(Issue 6) pp:3224-3229
Publication Date(Web):16 Apr 2014
DOI:10.1039/C4GC00243A
The key C–C bond forming step of the Rh-catalysed carboxylation of organoboron compounds with CO2 was investigated by density functional theory (DFT) at the IEFPCM/PBE0/DGDZVP level of theory. With a bidentate phosphane (dppp) ligand, the reaction begins with a transformation from square-planar O-(η1)-bonded to distorted-tetrahedral, η2-bonded CO2 followed by migratory insertion (barrier 12.7 kcal mol−1). The calculations showed that incorporation of electron-donating substituents within either the aryl substrate or the phosphane leads to a slight decrease of the reaction barrier, in excellent agreement with the experimental trends. With a diene ligand (cod), the migratory insertion proceeds directly from the O-(η1)-bonded CO2 (barrier 17.1 kcal mol−1) as a consequence of the diminished σ-donor ability of the diene ligand. Therefore, the diene ligand is predicted to be an inferior choice compared to the diphosphane. Testing of [(cod)Rh(OH)]2 upon completion of the computations showed no conversion.
Co-reporter: Hua-Li Qin;Xiao-Qing Chen;Yi-Zhen Huang; Eric Assen B. Kantchev
Chemistry - A European Journal 2014 Volume 20( Issue 40) pp:12982-12987
Publication Date(Web):
DOI:10.1002/chem.201402451
Abstract
First-principles modelling of the diastereomeric transition states in the enantiodiscrimination stage of the catalytic cycle can reveal intimate details about the mechanism of enantioselection. This information can be invaluable for further improvement of the catalytic protocols by rational design. Herein, we present a density functional theory (IEFPCM/PBE0/DGDZVP level of theory) modelling of the carborhodation step for the asymmetric 1,4-arylation of cyclic α,β-unsaturated ketones mediated by a [(binap)RhI] catalyst. The calculations completely support the older, qualitative, pictorial model predicting the sense of the asymmetric induction for both the chelating diphosphane (binap) and the more recent chiral diene (Phbod) ligands, while also permitting quantification of the enantiomeric excess (ee). The effect of dispersion interaction correction and basis sets has been also investigated. Dispersion-corrected functionals and solvation models significantly improve the predicted ee values.
Co-reporter:Gao-Feng Zha, Jia-Bin Han, Xiao-Qian Hu, Hua-Li Qin, Wan-Yin Fang and Cheng-Pan Zhang
Chemical Communications 2016 - vol. 52(Issue 47) pp:NaN7461-7461
Publication Date(Web):2016/04/21
DOI:10.1039/C6CC03040H
Silver-mediated direct trifluoromethoxylation of α-diazo esters and ketosteroid was disclosed. The reactions of alkyl α-diazo arylacetates with AgOCF3 or CF3SO2OCF3/AgF at −30 to 10 °C under a N2 atmosphere provided α-trifluoromethoxyl arylacetates in up to 90% yield, while alkyl α-diazo vinylacetates reacting with CF3SO2OCF3/AgF or AgOCF3 afforded γ-trifluoromethoxyl α,β-unsaturated esters in up to 94% yield. The α-diazo ketosteroid was also trifluoromethoxylated under the standard reaction conditions. This protocol allows for an effective and convenient access to a large number of synthetic building blocks, which are promising in the development of new functional OCF3-molecules.
Co-reporter:Gao-Feng Zha, Hua-Li Qin and Eric Assen B. Kantchev
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 10) pp:NaN2233-2233
Publication Date(Web):2017/02/01
DOI:10.1039/C6OB02651F
Atropisomeric biaryl disulfoxides contain two independent chiral elements. Previously, the (M,S,S)-diastereomer showed very high catalytic activity and selectivity in the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-enones whereas the (M,R,R) counterpart – none. Herein, DFT computations on the key transmetallation (turnover-determining) and carborhodation (enantioselectivity-determining) steps of the catalytic cycle show that the (M,S,S)-ligand gives rise to lower reaction barriers for these elementary steps. However, the barriers for the (M,R,R)-ligand are not sufficiently high to explain the lack of reactivity. Hence, this phenomenon is most likely due to the failure of catalyst formation from the ligand and the dimeric Rh precatalyst complex. The hitherto unknown (M,S,R)-ligand shows predicted enantioselectivity similar to the (M,S,S)-ligand as a consequence of lower reaction barriers associated with those isomers whose key features resemble the (M,S,S)-ligand.
![L-ISOLEUCINE, N-[(6-BROMO-2,3-DIHYDRO-1-OXO-1H-INDEN-4-YL)CARBONYL]-](http://img.cochemist.com/ccimg/863500/863489-95-6.png)
![L-ISOLEUCINE, N-[(6-BROMO-2,3-DIHYDRO-1-OXO-1H-INDEN-4-YL)CARBONYL]-](http://img.cochemist.com/ccimg/863500/863489-95-6_b.png)