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1.  Enantioselective Synthesis of Spiro[cyclohexane-1,3′-indolin]-2′-ones Containing Multiple Stereocenters via Organocatalytic Michael/Aldol Cascade Reactions 
Tetrahedron letters  2013;54(19):2311-2314.
Organocatalytic reactions of 3-olefinic oxindoles and pentane-1,5-dial were investigated to provide access to substituted spirocyclohexane oxindoles via Michael/Aldol cascade reactions. Of particular interest, we have examined the stereochemical outcome of electron withdrawing and electron-donating groups on the oxindole ring nitrogen. Interestingly, we have observed that the N-protecting group on the oxindole has critical effect on aldol ring closure leading to ultimate stereochemical outcome of the hydroxyl center. The overall process is quite efficient and afforded products with multiple stereocenters in high yields and excellent enantioselectivities (>99% ee).
PMCID: PMC4335313
Organocatalyst; Spiroindole; Michael reaction; Aldol reaction; Asymmetric catalysis
2.  An exclusive fluoride receptor: Fluoride-induced proton transfer to a quinoline-based thiourea 
Tetrahedron letters  2014;55(8):1467-1470.
A new quinoline-based tripodal thiourea has been synthesized, which exclusively binds fluoride anion in DMSO, showing no affinity for other anions including, chloride, bromide, iodide, perchlorate, nitrate and hydrogen sulfate. As investigated by 1H NMR, the receptor forms both 1:1 and 1:2 complex yielding the binding constants of 2.32(3) (in log β1) and 4.39(4) (in log β2), respectively; where quinoline groups are protonated by the fluoride-induced proton transfer from the solution to the host molecule. The 1:2 binding is due to the interactions of one fluoride with NH binding sites of urea sites and another fluoride with secondary +NH binding sites within the tripodal pocket. The formation of both 1:1 and 1:2 complexes has been confirmed by the theoretical calculations based on density functional theory (DFT).
PMCID: PMC3991426  PMID: 24753636
Fluoride sensor; Thiourea; Anion complex; Molecular recognition; Acyclic receptor
3.  A facile synthesis of bispyrroloquinone and bispyrroloiminoquinone ring system of marine alkaloids 
Tetrahedron letters  2009;50(25):3074-3076.
Bispyrroloquinone and bispyrroloiminoquinone are two important polycyclic ring systems present in biologically active marine alkaloids such as Zyzzyanones, tsitsikammamines and wakayin. A facile synthesis of these two ring systems starting from a 6-benzylamino indole-4,7-quinone or 6-benzylamino pyrroloiminoquinone is described here. This chemistry involves the construction of a pyrrole ring in a single step by treatment of the starting reagents with ethyl acetoacetate or phenylbutane-1,3-dione in the presence of ceric ammonium nitrate in MeOH/CH2Cl2 solvent.
PMCID: PMC4331033
4.  Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity 
Tetrahedron letters  2014;55(6):1154-1158.
A novel class of 6-indolypyridine-3-carbonitrilile derivatives were synthesized and evaluated for antiproliferative activities to establish structure-activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C2 position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity cells with IC50 values of 4.1–13.4 μM.
PMCID: PMC3963174  PMID: 24678129
Antiproliferative agents; Indole; Indolyl carbonitriles; Microwave-assisted Synthesis; Multicomponent Reactions
5.  Boc-protected 1-(3-oxocycloalkyl)ureas via a one-step Curtius rearrangement: mechanism and scope 
Tetrahedron letters  2013;55(4):842-844.
1-(3-Oxocyclobutyl) carboxylic acid (4a) was converted into N-Boc-protected 1-(3-oxocyclobutyl) urea (5a), a key intermediates for the preparation of agonists of metabotropic glutamate receptor 5, in one-step when treated with diphenyl phosphoryl azide and triethylamine in tert-butanol. The mechanism of the reaction involves a nucleophilic addition of the in situ generated tert-butyl carbamate to the isocyanate intermediate. This reaction is applicable to other 1-(3-oxocycloalkyl) carboxylic acids but not to linear γ-keto carboxylic acids.
PMCID: PMC3928826  PMID: 24563555
1-(3-Oxo)ureas; Curtius rearrangement; Carbamoylcarbamate; γ-Keto carboxylic acid; 1-(3-Oxocyclobutyl) carboxylic acid
6.  Carbamidocyclophanes F and G with Anti-Mycobacterium tuberculosis Activity from the Cultured Freshwater Cyanobacterium Nostoc sp. 
Tetrahedron letters  2014;55(3):686-689.
Two new (1 and 2) and three known (3–5) carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium Nostoc sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS as well as CD spectroscopy. Carbamidocyclophane F (1) showed potent anti-Mycobacterium tuberculosis activity in the microplate Alamar blue assay and low-oxygen-recovery assay with MIC values of 0.8 and 5.4 µM, respectively. Carbamidocyclophane F (1) also displayed antimicrobial activities against the gram positive bacteria Staphylococcus aureus and Enterococcus faecalis with MIC values of 0.1 and 0.2 µM, respectively. Carbamidocyclophane F (1) and Carbamidocyclophane G (2) both showed antiproliferative activity against MDA-MB-435 and HT-29 human cancer cell lines with IC50 values in the range from 0.5 to 0.7 µM.
PMCID: PMC4161986  PMID: 25225453
Cyanobacteria; Nostoc sp.; [7.7]paracyclophane; Anti- Mycobacterium tuberculosis Activity
7.  Synthesis and evaluation of antiproliferative activity of substituted N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides 
Tetrahedron letters  2013;55(2):373-375.
Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDA-MB-468) cells. Structure-activity relationship studies revealed that xanthone benzenesulfonamide hybrid compounds can be used for development of new lead anticancer agents.
PMCID: PMC3895536  PMID: 24453382
Antiproliferative Activity; Benzenesulfonamides; Cancer; Xanthone
8.  Julia-Kocienski Approach to Trifluoromethyl-Substituted Alkenes1 
Tetrahedron letters  2013;54(45):6008-6011.
A Julia-Kocienski approach to trifluoromethyl-substituted alkenes was evaluated in the reactions of 1,3-benzothiazol-2-yl, 1-phenyl-1H-tetrazol-5-yl, and 1-tbutyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfones with aldehydes. Among the various conditions tested, the best yields were obtained with 1-phenyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfone, in CsF-mediated, room temperature olefinations in DMSO. Aromatic aldehydes gave (trifluoromethyl)vinyl derivatives in 23-86% yields, with generally moderate stereoselectivity. Straightforward synthesis of the Julia-Kocienski reagent, and conversion to trifluoromethyl-substituted alkenes under mild reaction conditions, are the advantages of this approach.
PMCID: PMC4283945  PMID: 25568501
9.  Microwave-assisted, one-pot reaction of 7-azaindoles and aldehydes: a facile route to novel di-7-azaindolylmethanes 
Tetrahedron letters  2014;55(1):10.1016/j.tetlet.2013.10.143.
A novel and highly efficient synthetic method leveraging microwave-assisted organic synthesis (MAOS) to yield di-7-azaindolylmethanes (DAIMs) is reported. Under MAOS conditions, reaction of 7-azaindole with aldehydes resulted predominantly in DAIMs, as opposed to the expected 7-azaindole addition products that form at ambient temperature. Based upon studies of different indoles and azaindoles with various aromatic and aliphatic aldehydes, we herein propose a mechanism where rapid and efficient microwave heating promotes nucleophilicity of 7-azaindoles towards the corresponding alkylidene-azaindolene intermediate to form the DAIM. This sequence provides a versatile approach to efficiently synthesize novel DAIMs that may be useful pharmaceuticals.
PMCID: PMC3880151  PMID: 24396154
Microwave; 7-Azaindoles; Di-7-azaindolylmethanes; One-pot; reactions; MAOS
10.  Vanadium-catalyzed oxidative Strecker reaction: α-C–H cyanation of para-methoxyphenyl (PMP)-protected primary amines 
Tetrahedron letters  2013;55(1):10.1016/j.tetlet.2013.11.012.
We describe an oxidative Strecker reaction that allows for direct cyanation of para-methoxyphenyl (PMP)-protected primary amines. A vanadium(V) complex was used as the catalyst and TBHP as the oxidant. The cyanation occurs at the α-C position bearing either an alkyl or an aromatic group. This method provides a direct access to α-aminonitrile from amines with one-carbon extension.
PMCID: PMC3885172  PMID: 24415804
Vanadium catalyst; C–H cyanation; Oxidative Strecker reaction; Primary amine; Schiff base ligand
11.  Formal and total synthesis of (±)-cycloclavine 
Tetrahedron letters  2013;56(1):197-199.
A ring fragmentation and intramolecular azomethine ylide 1,3-dipolar cycloaddition sequence of reactions was successfully used in the preparation of a known (±)-cycloclavine precursor in good overall yield. Results of efforts to incorporate the tetrasubstituted cyclopropane ring present in cycloclavine are also discussed.
PMCID: PMC3915717  PMID: 24511164
Cycloclavine; Ergot Alkaloid; Natural Product Synthesis; Ring Fragmentation; 1,3-Dipolar Cycloaddition
12.  Base mediated deprotection strategies for trifluoroethyl (TFE) ethers, a new alcohol protecting group 
Tetrahedron letters  2013;54(51):10.1016/j.tetlet.2013.10.097.
A trifluoroethyl (TFE) ether is specifically introduced as a protecting group in organic chemistry. Its first strategic application and removal in the total synthesis of vinigrol is discussed. Two lithium base mediated deprotection strategies for its removal are presented in this Letter. In one deprotection approach, the trifluoroethyl ether is converted to a difluorovinyl ether and then catalytically cleaved using osmium tetraoxide, while in the second approach a difluorovinyl anion is formed and trapped with an electrophilic oxygen reagent (MoOPH) to form a labile difluoroacetate. To further aid the reader, a summary of approaches for forming trifluoroethyl ethers is included as well as a discussion of alternate deprotection strategies.
PMCID: PMC3878608  PMID: 24391289
Trifluoroethyl ether; Difluorovinyl; Deprotection; Dihydroxylation; Electrophilic oxygen
13.  Preparation of C-arylglycals via Suzuki-Miyaura cross-coupling of dihydropyranylphosphates 
Tetrahedron letters  2013;54(50):6889-6891.
The preparation of C-arylglycals has been accomplished employing the Suzuki-Miyaura cross-coupling reaction of dihydropyranylphosphates with arylboronate esters. The reaction is tolerant of both electron-donating (EDG) and electron-withdrawing (EWG) groups on the aromatic ring and affords the corresponding C-arylglycals in good to excellent yields (68-97%). Additionally, the ketene acetal phosphate derived from 6-deoxy-3,4-di-O-benzyl-L-rhamnal also couples efficiently to yield C-arylglycals in excellent yields.
PMCID: PMC4080724  PMID: 24999287
carbohydrates; deoxysugars; glycosides; natural products; Suzuki-Miyaura
14.  A simple one-pot 2-step N-1-alkylation of indoles with α-iminoketones toward the expeditious 3-step synthesis of N-1-quinoxaline-indoles 
Tetrahedron letters  2013;54(49):10.1016/j.tetlet.2013.09.113.
A straightforward procedure for the preparation of N-quinoxaline-indoles is presented. A base-catalyzed one-pot addition of indoles to a preformed α-iminoketone proceeds on the N-1 indole and the subsequent adduct undergoes an acid-mediated deprotection of an internal amino nucleophile, intramolecular cyclization and final oxidation generating N-1-quinoxaline-indoles in good yield.
PMCID: PMC3855464  PMID: 24327792
Multicomponent reaction; Indole; Quinoxaline; α-iminoketone; Privileged scaffolds
15.  Three-step synthesis of an annulated β-carboline via palladium catalysis 
Tetrahedron letters  2013;54(48):10.1016/j.tetlet.2013.09.108.
The synthesis of β–carbolines is a mature field, yet new methods are desirable to introduce new functionality onto the core scaffold. We describe the incorporation of an additional fused ring onto the β–carboline via a novel palladium-catalyzed, one-pot Sonogashira coupling/intramolecular [2+2+2] cyclization. This method generates three rings in one flask and produces an annulated β–carboline in 80% yield. A preliminary mechanistic study into the sequence of events is described, which confirms an unprecedented catalytic role for palladium.
PMCID: PMC3861870  PMID: 24347695
β-carboline; cyclotrimerization; Sonogashira coupling; palladium catalysis; heteroannulation
16.  N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate as a highly active and selective esterification catalyst 
Tetrahedron letters  2013;54(48):10.1016/j.tetlet.2013.09.132.
N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate (1) was found to be a very active esterification catalyst that promotes condensation of equal mole amount of carboxylic acids and alcohols under mild conditions. This catalyst is also highly selective towards carboxylic acid and alcohol substrates at ambient temperature.
PMCID: PMC3864184  PMID: 24357885
esterification; catalyst; selectivity; anilinium p-toluenesulfonate
17.  Microwave-assisted Expeditious and Efficient Synthesis of Cyclopentene Ring-fused Tetrahydroquinoline Derivatives Using Three-component Povarov Reaction 
Tetrahedron letters  2013;54(48):10.1016/j.tetlet.2013.09.107.
We report here an efficient and expeditious microwave-assisted synthesis of cyclopentadiene ring-fused tetrahydroquinolines using the three-component Povarov reaction catalyzed by indium (III) chloride. This method has an advantage of shorter reaction time (10 – 15 min) with high and reproducible yields (up to 90%) and is suitable for parallel library synthesis. The optimization process is reported and the results from the microwave route are compared with those of the conventional synthetic route. In almost all cases, the microwave acceleration consistently provided improved yields favoring the cis-diastereomer.
PMCID: PMC3887467  PMID: 24421568
Tetrahydroquinolines; Cyclopentene ring-fused tetrahydroquinolines; Microwave-assisted synthesis; Parallel synthesis; Povarov reaction
18.  Karlotoxin synthetic studies: concise synthesis of a C(42–63) B-ring tetrahydropyran fragment 
Tetrahedron letters  2013;54(48):10.1016/j.tetlet.2013.09.104.
Starting from natural D-mannose, a C(42–63) B-ring tetrahydropyran fragment in karlotoxin 2 has been prepared via a common THP intermediate in a concise manner. E-selective Julia–Kocienski olefination efficiently assembled a C(51–63) chlorodiene subunit and a C(42–50) tetrahydropyran segment.
PMCID: PMC3873160  PMID: 24376284
Polyketide; Karlotoxin; Tetrahydropyran; D-Mannose; Julia-Kocienski olefination
19.  Selective trapping of SNO-BSA and GSNO by benzenesulfinic acid sodium salt: mechanistic study of thiosulphonate formation and feasibility as a protein S-nitrosothiol detection strategy 
Tetrahedron letters  2013;54(42):10.1016/j.tetlet.2013.08.011.
The conversion of S-nitrosothiols to thiosulphonates by reaction with the sodium salt of benzenesulfinic acid (PhSO2Na) has been examined in detail with the exemplary substrates S-nitrosoglutathione (GSNO) and S-nitrosylated bovine serum albumin (SNO-BSA). The reaction stoichiometry (2:1, PhSO2Na:RSNO) and the rate law (first order in both PhSO2Na and RSNO) have been determined under mild acidic conditions (pH 4.0). The products have been identified as the corresponding thiosulphonates (GSSO2Ph and BSA-SSO2Ph) along with PhSO2NHOH obtained in a 1:1 ratio. GSH, GSSG, and BSA were unreactive to PhSO2Na.
PMCID: PMC3811913  PMID: 24187391
S-nitrosothiols; Benzenesulfinic acid; S-phenylthiosulphonates; Protein labeling
20.  Organocatalyzed asymmetric Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes 
Tetrahedron letters  2013;54(42):10.1016/j.tetlet.2013.08.015.
The first enantioselective Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes has been brealized by using a new bifunctional Takemoto-type thiourea catalyst. The primary Michael adducts obtained were converted in situ to the corresponding amides through the aminolysis. High yields, excellent diastereoselectivities (>95:5 dr), and good enantioselectivities (up to 81% ee) have been achieved for the corresponding α ,β-disubstituted γ-nitroamides. This reaction againdemon strated that α-ketophosphonates are interesting pronucleophiles that can be used as amide surrogates in organocatalyzed reactions.
PMCID: PMC3810965  PMID: 24187390
Michael reaction; Organocatalysis; α-Ketophosphonate; Nitroalkene; Enantioselective; Amide surrogate
21.  Total Syntheses of Proposed (±)-Trichodermatides B and C 
Tetrahedron letters  2013;54(41):10.1016/j.tetlet.2013.07.137.
Total syntheses of putative (±)-trichodermatides B and C are described. These efficient syntheses feature the oxa-[3 + 3] annulation strategy, leading to B and C along with their respective C2-epimers. However, these synthetic samples are spectroscopically very different from the natural products. DFT calculations of C13 chemical shifts are conducted and the predicted values are in good agreement with those of synthetic samples, thereby questioning in the accuracy of structural assignments of trichodermatides B and C.
PMCID: PMC3818125  PMID: 24223440
Trichodermatides; oxa-[3 + 3] annulation; biosynthesis; Davis’ oxaziridine; electrocyclic ring-opening; DFT calculations
22.  A cytotoxic dimeric furanoheliangolide from Piptocoma rufescens 
Tetrahedron letters  2013;54(40):5457-5460.
A new sesquiterpene lactone, rufescenolide C (1), the first furanoheliangolide dimer, was isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. Its structure was determined by analysis of its spectroscopic data, with the absolute configuration being established by analysis of the CD spectrum. A plausible biogenesis of this dimer is proposed. This compound showed potent cytotoxicity with an IC50 value of 150 nM, when tested against HT-29 human colon cancer cells.
PMCID: PMC3804354  PMID: 24159245
Piptocoma rufescens; Furanoheliangolide dimer; Cytotoxicity
23.  Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling 
Tetrahedron letters  2013;54(8):913-917.
An efficient total synthesis of the annulated indole natural product (±)-cis-trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal-halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber-Batcho indole synthesis.
PMCID: PMC4179867  PMID: 25278636
Indole; aryne; benzofuran; trikentrin; herbindole; natural products; cycloaddition; total synthesis; Stille; cross-coupling
24.  Regioselectivity of Diels-Alder Reactions Between 6,7-Dehydrobenzofuran and 2-Substituted Furans 
Tetrahedron letters  2012;53(31):4022-4025.
We describe the first report of the generation of 6,7-dehydrobenzofuran (6,7-benzofuranyne) from 6,7-dihalobenzofurans via metal-halogen exchange and elimination, in a manner similar to our previous work with 6,7-indole arynes. This benzofuranyne undergoes highly regioselective Diels-Alder cycloadditions with 2-substituted furans.
PMCID: PMC4179875  PMID: 25278635
25.  Dicarboxylated ethynylarenes as buffer-dependent chemosensors for Cd(II), Pb(II) and Zn(II) 
Tetrahedron letters  2013;54(39):5366-5369.
Two dicarboxylated ethynylarenes were prepared efficiently from condensation of 1,3-bis(3-aminoph enylethynyl)benzene with two equivalents of either succinic anhydride or glutaric anhydride. These compounds behave as fluorescent chemosensors selective for Cd(II), Pb(II) and Zn(II) cations under buffered aqueous conditions, with analyte binding observed as bathochromically shifted, intensified fluorescence. It was noteworthy that the fluorescence responses varied significantly with buffer identity. A conformational restriction mechanism involving reversible interactions between the fluorophore, metal cation and buffer itself is proposed.
PMCID: PMC3805260  PMID: 24163484
Sensor; Fluorescent; Ratiometric; Cation detection; Ethynylarene

Results 1-25 (547)