- Enantioselective Palladium-Catalyzed Hydrophosphinylation of Allenes with Phosphine Oxides: Access to Chiral Allylic Phosphine Oxides
-
A Pd-catalyzed hydrophosphinylation of alkyl and aryl-oxyallenes with phosphine oxides has been developed for the efficient and rapid construction of a family of chiral allylic phosphine oxides with a diverse range of functional groups. This methodology was further applied in the facile construction of chiral 2H-chromene and later stage functionalization of cholesterol.
- Wang, Jun,Yang, Zhiping
-
supporting information
p. 27288 - 27292
(2021/11/17)
-
- Stereoselective Synthesis of Dysoxylactam A
-
The first report on the stereoselective synthesis of dysoxylactam A is disclosed. The five stereogenic centers of the fatty acid chain are created by utilizing Merck-Carreira and Marshall's propargylation reaction, Evans' alkylation methodology, and Noyor
- Chandankar, Somnath S.,Raghavan, Sadagopan
-
supporting information
p. 653 - 655
(2020/01/31)
-
- Enantioselective Addition of Alkynyl Esters and Ethers to Aldehydes Catalyzed by a Cyclopropyl Amino Alcohol Based Zinc Catalyst
-
A novel and highly enantioselective synthesis of hydroxyalkynyl esters and ethers through the asymmetric addition of alkynyl esters or ethers to aldehydes promoted by a cyclopropyl amino alcohol based zinc catalyst has been developed. The method afforded a library of new enantioenriched hydroxyalkynol esters and ethers (up to 93percent yield; 95percent ee), and it was compatible with a broad range of functional groups. Moreover, it could be used in the synthesis of carbon-chain-elongated enantioenriched hydroxyalkynol esters and (2 R,5 R)-musclide-A1, a cardiotonic potentiating principle from musk.
- Bian, Qinghua,Li, Fengqi,Li, Shuoning,Ma, Sijie,Walsh, Patrick J.,Wang, Lifeng,Wang, Min,Zhong, Jiangchun,Zhou, Yun
-
supporting information
p. 60 - 64
(2019/12/30)
-
- The synthesis of unnatural α-alkyl- And α-aryl-substituted serine derivatives
-
The synthesis of α-aryl- and α-alkyl-substituted serine derivatives via [3,3]-sigmatropic rearrangement of allyl carbamates as a key step is reported. Allyl carbamates were obtained from the corresponding allyl alcohols. The former were prepared through three approaches. Aryl-substituted ones were synthesized via the Stille coupling reaction of aryl iodides with enantiomerically enriched vinyl stannanes. Conversely, alkyl-substituted allyl alcohols were prepared by an analogous strategy involving the Negishi coupling reaction of enantiomerically enriched vinyl iodides or by enzymatic kineric resolution of the corresponding racemic alcohols.
- Narczyk, Aleksandra,Stecko, Sebastian
-
supporting information
p. 1204 - 1213
(2020/02/22)
-
- Streamlined Catalytic Enantioselective Synthesis of α-Substituted β,γ-Unsaturated Ketones and Either of the Corresponding Tertiary Homoallylic Alcohol Diastereomers
-
A widely applicable, practical, and scalable strategy for efficient and enantioselective synthesis of β,γ-unsaturated ketones that contain an α-stereogenic center is disclosed. Accordingly, aryl, heteroaryl, alkynyl, alkenyl, allyl, or alkyl ketones that contain an α-stereogenic carbon with an alkyl, an aryl, a benzyloxy, or a siloxy moiety can be generated from readily available starting materials and by the use of commercially available chiral ligands in 52-96% yield and 93:7 to >99:1 enantiomeric ratio. To develop the new method, conditions were identified so that high enantioselectivity would be attained and the resulting α-substituted NH-ketimines, wherein there is strong CN → B(pin) coordination, would not epimerize before conversion to the derived ketone by hydrolysis. It is demonstrated that the ketone products can be converted to an assortment of homoallylic tertiary alcohols in 70-96% yield and 92:8 to >98:2 dr - in either diastereomeric form - by reactions with alkyl-, aryl-, heteroaryl-, allyl-, vinyl-, alkynyl-, or propargyl-metal reagents. The utility of the approach is highlighted through transformations that furnish other desirable derivatives and a concise synthesis route affording more than a gram of a major fragment of anti-HIV agents rubriflordilactones A and B and a specific stereoisomeric analogue.
- Pozo, Juan Del,Zhang, Shaochen,Romiti, Filippo,Xu, Shibo,Conger, Ryan P.,Hoveyda, Amir H.
-
supporting information
p. 18200 - 18212
(2020/11/02)
-
- Inhibition of Mycobacterium tuberculosis InhA: Design, synthesis and evaluation of new di-triclosan derivatives
-
Multi-drug resistant tuberculosis (MDR-TB) represents a growing problem for global healthcare systems. In addition to 1.3 million deaths in 2018, the World Health Organisation reported 484,000 new cases of MDR-TB. Isoniazid is a key anti-TB drug that inhibits InhA, a crucial enzyme in the cell wall biosynthesis pathway and identical in Mycobacterium tuberculosis and M. bovis. Isoniazid is a pro-drug which requires activation by the enzyme KatG, mutations in KatG prevent activation and confer INH-resistance. ‘Direct inhibitors’ of InhA are attractive as they would circumvent the main clinically observed resistance mechanisms. A library of new 1,5-triazoles, designed to mimic the structures of both triclosan molecules uniquely bound to InhA have been synthesised. The inhibitory activity of these compounds was evaluated using isolated enzyme assays with 2 (5-chloro-2-(4-(5-(((4-(4-chloro-2-hydroxyphenoxy)benzyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenoxy)phenol) exhibiting an IC50 of 5.6 μM. Whole-cell evaluation was also performed, with 11 (5-chloro-2-(4-(5-(((4-(cyclopropylmethoxy)benzyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenoxy)phenol) showing the greatest potency, with an MIC99 of 12.9 μM against M. bovis.
- Alderwick, Luke J.,Armstrong, Tom,Lamont, Malcolm,Lanne, Alice,Thomas, Neil R.
-
supporting information
(2020/09/18)
-
- BTK Inhibitors and uses thereof
-
The invention discloses a bruton's tyrosine kinase (BTK) inhibitor and use thereof. Specifically, the invention provides heteroaromatic compounds or stereoisomers, geometrical isomers, tautomers, racemates, nitrogen oxides, hydrates, solvates, metabolites and pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the heteroaromatic compounds; the invention also discloses use of the heteroaromatic compounds or the pharmaceutical compositions containing the heteroaromatic compounds in preparation of medicines; the medicines can be used for treating autoimmune diseases, inflammatory diseases or proliferative diseases.
- -
-
Paragraph 1201-1205
(2020/05/02)
-
- Reductive Etherification of Aldehydes and Ketones with Alcohols and Triethylsilane Catalysed by Yb(OTf)3: an Efficient One-Pot Benzylation of Alcohols
-
The one-pot synthesis of symmetrical and unsymmetrical ethers from aldehydes and ketones can be conveniently performed using Yb(OTf)3 as catalyst and triethylsilane as reducing agent in presence of alcohols. This methodology leads to the synthesis of ether derivatives with good yields. Notably, this process resulted a useful tool to protect alcohols as benzyl ether derivatives using differently substituted benzaldehydes as protecting agents under mild conditions. A plausible mechanism was also proposed. (Figure presented.).
- Pelosi, Azzurra,Lanari, Daniela,Temperini, Andrea,Curini, Massimo,Rosati, Ornelio
-
supporting information
p. 4527 - 4539
(2019/08/26)
-
- Novel glucopyranoside C2-derived 1,2,3-triazoles displaying selective inhibition of O-GlcNAcase (OGA)
-
O-GlcNAcylation or O-GlcNAc modification is a post-translational modification of several proteins responsible for fundamental cellular processes. Dysregulation of the O-GlcNAc pathway has been linked to the etiology of several diseases such as neurodegenerative and cardiovascular diseases, type 2 diabetes and cancer. O-GlcNAcase (OGA) catalyzes the removal of O-GlcNAc from the modified proteins and several carbohydrate-based OGA inhibitors have been synthesized to understand the role of O-GlcNAc-modified proteins in physiological and pathological conditions. However, many of the inhibitors lack selectivity for OGA over lysosomal hexosaminidases A and B. Aiming the selectively inhibition of OGA, we propose herein the synthesis of twelve novel glucopyranoside derivatives exploring the bioisosteric replacement of the GlcNAc 2-acetamide group by 1,4-disubstituted 1,2,3-triazole ring, bearing a variety of central chains with different shapes. Compounds were readily prepared through “Copper(I) Catalyzed Azide/Alkyne Cycloaddition” (CuAAC) reaction between a sugar azide and different terminal alkynes. Initial Western Blot analyses and further inhibitory assays proved that compounds 6a (IC50 = 0.50 ± 0.02 μM, OGA), 6k (IC50 = 0.52 ± 0.01 μM, OGA) and 6l (IC50 = 0.72 ± 0.02 μM, OGA) were the most potent and selective compounds of the series. Structure-activity relationship analyses and molecular docking simulations demonstrated that the bridge of two-carbon atoms between the C-4 position of the triazole and the phenyl ring (6a), which may be replaced by heteroatoms such as N (6k) or O (6l), is fundamental for accommodation and inhibition within OGA catalytic pocket.
- Igual, Michelle O.,Nunes, Paulo S.G.,da Costa, Rafael M.,Mantoani, Susimaire P.,Tostes, Rita C.,Carvalho, Ivone
-
-
- An Atom-Economic and Stereospecific Access to Trisubstituted Olefins through Enyne Cross Metathesis Followed by 1,4-Hydrogenation
-
The combination of intermolecular enyne cross metathesis and subsequent 1,4-hydrogenation opens a stereocontrolled and atom-economic access to trisubstituted olefins. By investigating different combinations of functionalized alkyne and alkene substrates, we found that the outcome (yield, E / Z ratio) of the Grubbs II-catalyzed enyne cross-metathesis step depends on the substrate's structure, the amount of the alkene (used in excess), and the (optional) presence of ethylene. In any case, the 1,4-hydrogenation, catalyzed by 1,2-dimethoxybenzene-Cr(CO) 3, proceeds stereospecifically to yield exclusively the E -products from both the E- and Z- 1,3-diene intermediates obtained by metathesis. A rather broad scope and functional group compatibility of the method is demonstrated by means of 15 examples.
- Ratsch, Friederike,Schmalz, Hans-Günther
-
supporting information
p. 785 - 792
(2018/01/27)
-
- Process Optimization for the Large-Scale Preparation of (2 S,3 aR,7 aS)- tert-Butyl Hexahydro-2,5-methanopyrrolo[3,2- c]pyridine-1(4 H)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists
-
An optimized large-scale synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate (1A), an important intermediate for nicotinic acetylcholine receptor agonists, is described. The key feature of the synthesis involves three transformations in a one-pot process, including debenzylation and ring hydrogenation of two fused bicyclic rings. Multihundred gram quantities of 1A were prepared.
- Jarugu, Lokesh Babu,Reddy, China Anki,Chikkananjunda, Nanjundaswamy Kanikahalli,Krishnamoorthy, Suresh,Sarvanakumar, Pon,Sankar, Ulaganathan,Arunachalam, Pirama Nayagam,McDonald, Ivar M.,Olson, Richard E.,Rampulla, Richard,Mathur, Arvind,Gupta, Anuradha
-
supporting information
p. 1276 - 1281
(2018/09/25)
-
- Inhibitors against Fungal Cell Wall Remodeling Enzymes
-
Fungal β-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inh
- Delso, Ignacio,Valero-Gonzalez, Jessika,Gomollón-Bel, Fernando,Castro-López, Jorge,Fang, Wenxia,Navratilova, Iva,van Aalten, Daan M. F.,Tejero, Tomás,Merino, Pedro,Hurtado-Guerrero, Ramon
-
supporting information
p. 128 - 132
(2018/02/06)
-
- Synthesis of Functionalized 1,3-Butadienes via Pd-Catalyzed Cross-Couplings of Substituted Allenic Esters in Water at Room Temperature
-
An environmentally responsible, mild method for the synthesis of functionalized 1,3-butadienes is presented. It utilizes allenic esters of varying substitution patterns, as well as a wide range of boron-based nucleophiles under palladium catalysis, generating sp-sp2, sp2-sp2, and sp2-sp3 bonds. Functional group tolerance measured via robustness screening, along with room temperature and aqueous reaction conditions highlight the methodology's breadth and potential utility in synthesis.
- Lippincott, Daniel J.,Linstadt, Roscoe T. H.,Maser, Michael R.,Gallou, Fabrice,Lipshutz, Bruce H.
-
supporting information
p. 4719 - 4722
(2018/08/23)
-
- Cyclopropanation of Benzene Rings by Oxidatively Generated α-Oxo Gold Carbene: One-Pot Access to Tetrahydropyranone-Fused Cycloheptatrienes from Propargyl Benzyl Ethers
-
Cyclopropanations of benzene rings by oxidatively generated α-oxo gold carbenes are for the first time demonstrated in a Buchner reaction, in which readily available propargyl benzyl ethers are converted in one-pot to tetrahydropyranone-fused cycloheptatrienes via sequential oxidative gold catalysis and base-promoted isomerization. Additional examples of arene cyclopropanations without fragmentation of the cyclopropane ring are also realized. (Figure presented.).
- Ji, Kegong,Zhang, Liming
-
supporting information
p. 647 - 651
(2017/12/26)
-
- Regioselective Arene and Heteroarene Functionalization: N-Alkenoxypyridinium Salts as Electrophilic Alkylating Agents for the Synthesis of α-Aryl/α-Heteroaryl Ketones
-
A direct regioselective functionalization of arenes and heteroarenes using N-alkenoxypyridinium salts as electrophilic alkylating agents for the synthesis of α-aryl/heteroaryl ketones has been developed. The method generates alkylating agents from alkynes and N-pyridine oxide followed by site-selective electrophilic substitution with a broad range of arenes and heteroarenes including benzene derivates, phenols, ethers, indoles, pyrroles, furans, and thiophenes in one pot. Kinetic isotope effect measurements and DFT studies reveal that this reaction likely proceeds through a carbon-cation intermediate.
- Zhai, Rong L.,Xue, Yun S.,Liang, Ting,Mi, Jia J.,Xu, Zhou
-
supporting information
p. 10051 - 10059
(2018/07/30)
-
- First stereoselective total synthesis and reconfirmation of absolute structure of nonenolide (?)-stagonolide D
-
The first stereoselective total synthesis of nonenolide (?)-stagonolide D has been accomplished. Midland Alpine borane reduction to install hydroxyl group at C4, Henbest epoxidation to introduce epoxide stereoselectively between C7 and C8, Yamaguchi ester
- Sravanth Kumar,Praneeth,Srihari,Yadav
-
p. 509 - 511
(2017/01/16)
-
- AMINO COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and Γ" or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
- -
-
Paragraph 0474
(2017/03/14)
-
- ETHER COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I? or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
- -
-
Paragraph 0560
(2017/03/14)
-
- CARBAMATE, ESTER, AND KETONE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I'" or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduce the excessive activation of complement.
- -
-
Paragraph 0510
(2017/03/14)
-
- ALKYNE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I'" or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduce the excessive activation of complement.
- -
-
Paragraph 0566; 0598; 0599
(2017/03/14)
-
- AMIDE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I"' or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit o
- -
-
Paragraph 0485
(2017/03/14)
-
- PHOSPHONATE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I''' or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit
- -
-
Paragraph 0603
(2017/03/14)
-
- ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
-
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I'" or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
- -
-
Paragraph 0612
(2017/03/14)
-
- Synthesis of Functionalized [3], [4], [5] and [6]Dendralenes through Palladium-Catalyzed Cross-Couplings of Substituted Allenoates
-
A mild method for the synthesis of highly functionalized [3]–[6]dendralenes is reported, representing a general strategy to diversely substituted higher homologues of the dendralenes. The methodology utilizes allenoates bearing various substitution patter
- Lippincott, Daniel J.,Linstadt, Roscoe T. H.,Maser, Michael R.,Lipshutz, Bruce H.
-
supporting information
p. 847 - 850
(2017/01/14)
-
- Pd-Catalyzed Hydroamination of Alkoxyallenes with Azole Heterocycles: Examples and Mechanistic Proposal
-
Palladium-catalyzed regio- and enantioselective addition of azole heterocycles to alkoxyallenes was developed (up to 92% yields and up to 94% ee). DFT calculations suggest a new Pd(0)-driven mechanistic pathway proceeding through protonation of the Pd-coo
- Bernar, Ivan,Fiser, Béla,Blanco-Ania, Daniel,Gómez-Bengoa, Enrique,Rutjes, Floris P. J. T.
-
supporting information
p. 4211 - 4214
(2017/08/23)
-
- C-F bond cleavage enabled redox-neutral [4+1] annulation via C-H bond activation
-
Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
- Wang, Cheng-Qiang,Ye, Lu,Feng, Chao,Loh, Teck-Peng
-
supporting information
p. 1762 - 1765
(2017/02/15)
-
- n-Butyllithium-promoted regioselective elimination of vicinal bis-triflate having an adjacent ether oxygen
-
Regioselective elimination of a vicinal bis-triflate having an adjacent ether oxygen functional group has been developed. Considered in the context of our studies of the regioselective elimination of vicinal dibromide, the key to the mechanism involves the electron-withdrawing inductive effect of the neighboring oxygen functional group. Aliphatic vinyl triflate was shown to be effective in Suzuki–Miyaura cross coupling compared with corresponding aliphatic vinyl bromide.
- Kutsumura, Noriki,Shibuya, Kota,Yamaguchi, Hitoshi,Saito, Takao
-
p. 4099 - 4102
(2017/09/28)
-
- Transformation of Carbonyl Compounds into Homologous Alkynes under Neutral Conditions: Fragmentation of Tetrazoles Derived from Cyanophosphates
-
Cyanophosphates (CPs) can be easily prepared from either ketones or aldehydes, and their reaction with NaN3-Et3N·HCl results in the formation of azidotetrazoles. Under microwave irradiation, successive fragmentation of the azidotetrazoles generates alkylidene carbenes that undergo [1,2]-rearrangement and are transformed into homologous alkynes. Treatment of ketone-derived CPs with TMSN3 and Bu2SnO as catalyst in toluene at reflux directly yields the corresponding internal alkynes, whereas the reaction of aldehyde-derived CPs with NaN3-Et3N·HCl in THF at reflux or TMSN3-Bu2SnO (cat.) in toluene at reflux provides homologous terminal alkynes in good yields. These reactions take place under neutral conditions and can be successfully extended to obtain alkynes that are not usually accessible from the corresponding carbonyl compounds by the Ohira-Bestmann or Shioiri procedures, which require basic conditions.
- Yoneyama, Hiroki,Numata, Masahiro,Uemura, Kenji,Usami, Yoshihide,Harusawa, Shinya
-
p. 5538 - 5556
(2017/06/07)
-
- PREPARATION AND USE OF CYCLIC SULFONAMIDE DERIVATIVES AS PAR-1 RECEPTOR ANTAGONISTS
-
Cyclic sulfonamide derivatives of Formula (I) or a pharmaceutically acceptable salt thereof are disclosed.
- -
-
Page/Page column 33
(2016/11/07)
-
- Zinc Iodide-Mediated Direct Synthesis of 2,3-Dihydroisoxazoles from Alkynes and Nitrones
-
A zinc diiodide (ZnI2)-mediated direct synthesis of 2,3-dihydroisoxazoles via a [3+2] cycloaddition reaction of the nitrones and non-electron-deficient terminal alkynes has been developed. This method was applied in the formal synthesis of HPA-12 and aminoglucose.
- Xiao, Zu-Feng,Ding, Ting-Hui,Mao, Sheng-Wei,Ning, Xiao-Shan,Kang, Yan-Biao
-
supporting information
p. 1859 - 1863
(2016/06/09)
-
- Chemo-, regio-, and stereoselective hydroboration of conjugated enyne alcohol/amine: Facile synthesis of Z,Z-/Z,E-1,3-dien-1/2-ylboronic ester bearing hydroxyl/amino group
-
Hydroboration of conjugated enyne alcohol/amine is studied by using copper salts and bis(pinacolato)diboron as pre-catalysts and boron source respectively. It is suggested that the chemo-selectivity is derived from a combined electronic influence of the heteroatoms on the substrate and the ligand on the transition metal. The regioselectivity is probably dominated mainly by electronic effect of the alkyne substituent. This study resulted in a highly selective protocol to access Z,Z-/Z,E-1,3-dien-1/2-ylboronic ester bearing hydroxyl/amino group.
- Xu, Hua-Dong,Wu, Hao,Jiang, Chun,Chen, Peng,Shen, Mei-Hua
-
supporting information
p. 2915 - 2918
(2016/06/14)
-
- N-Tosyl-1,5,2,6-dithiadiazocane: A waste-free electrophilic sulfur reagent for the efficient synthesis of medium-ring S,N-heterocycles
-
We report on the application of an eight-membered C2-symmetric sulfenamide derivative as a new convenient and highly reactive electrophilic sulfur-nucleophilic nitrogen synthon for the concise synthesis of medium-ring S,N-heterocyclic systems.
- Javorskis, Tomas,Bagd?iunas, Gintautas,Orentas, Edvinas
-
supporting information
p. 4325 - 4328
(2016/03/22)
-
- One-pot synthesis of benzene-fused medium-ring ketones: Gold catalysis-enabled enolate umpolung reactivity
-
Enolate umpolung reactivities offer valuable and potentially unique alternatives over the enolate counterparts for the construction of ubiquitous carbonyl compounds. We disclose here that N-alkenoxypyridinium salts, generated readily upon gold-catalyzed additions of protonated pyridine N-oxide to C-C triple bonds of unactivated terminal alkynes, display versatile enolate umpolung chemistry upon heating and react with tethered arene nucleophiles in an SN2′ manner. In a synthetically efficient one-pot, two-step process, this chemistry enables expedient preparation of valuable benzo-fused seven-/eight-membered cyclic ketones, including those of O-/Nheterocycles, from easily accessible aryl-substituted linear alkyne substrates. The reaction yields can be up to 87%.
- Xu, Zhou,Chen, Hongyi,Wang, Zhixun,Ying, Anguo,Zhang, Liming
-
supporting information
p. 5515 - 5518
(2016/05/24)
-
- Alkene-directed N-attack chemoselectivity in the gold-catalyzed [2+2+1]-annulations of 1,6-enynes with N-hydroxyanilines
-
Kinetically unstable nitrones are generated from gold-catalyzed reactions of 1,6-enynes with N-hydroxyanilines, and subsequently trapped by tethered alkenes to furnish [2+2+1]-annulations. Our experimental data reveal that such nitrones arise from atypical N-attack chemoselectivity that is triggered by tethered alkenes to facilitate the key protodeauration reaction. Kinetically unstable nitrones are generated from gold-catalyzed reactions of 1,6-enynes with N-hydroxyanilines, and subsequently trapped by tethered alkenes to furnish [2+2+1]-annulations. These findings open the door to new ways to access ketone nitrones with good stereoselectivity.
- Huple, Deepak B.,Mokar, Bhanudas D.,Liu, Rai-Shung
-
supporting information
p. 14924 - 14928
(2016/02/05)
-
- Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids
-
MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has developed resistance against the currently available drugs. Interestingly, a series of 35 metronidazole-triazole hybrids on screening against MRSA were found to be active. Compound 22 was found to be effective at 4 μg/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced upto 1 μg/mL when this compound was used in combination with oxacillin in 1:1 ratio. All the compounds were found to be non-toxic in THP-1 cell line upto a concentration of 50 μM. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies show that these compounds interact with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a crystal structure from MRSA.
- Negi, Beena,Kumar, Deepak,Kumbukgolla, Widuranga,Jayaweera, Sampath,Ponnan, Prija,Singh, Ramandeep,Agarwal, Sakshi,Rawat, Diwan S.
-
p. e426 - e437
(2016/04/19)
-
- Nucleophile-selective cross-coupling reactions with vinyl and alkynyl bromides on a dinucleophilic aromatic substrate
-
A nucleophile-selective cross-coupling reaction on an aromatic compound bearing two metal groups, Bpin and SnMe3, has been developed. Previously, only aryl bromides and iodides could be used as electrophilic components, but in this work, the scope could be extended to vinyl and alkynyl bromides as electrophiles. This means that the roles typical in Sonogashira couplings or Heck reactions of the aromatic ring as the dielectrophile coupling to vinyl and alkynyl metal species are reversed, which presents a new tool for organic synthesis. The first nucleophilic site to react is the stannyl group, and subsequently, a Suzuki-Miyaura cross-coupling reaction can take place on the same molecule.
- He, Lu-Ying,Schulz-Senft, Mathias,Thiedemann, Birk,Linshoeft, Julian,Gates, Paul J.,Staubitz, Anne
-
supporting information
p. 2498 - 2502
(2015/04/22)
-
- Novel One-Pot Synthetic Method for Propargyl Alcohol Derivatives from Allyl Alcohol Derivatives
-
An efficient one-pot procedure for the synthesis of propargyl alcohol derivatives from allyl alcohol derivatives has been developed. The key to this transformation from a C-C double bond to a C-C triple bond is that hydrogen bromide elimination from 1,2-dibromoalkanes that contain a neighboring oxygen functional group is promoted by the inductive electron-withdrawing effect of the oxygen functional group. In the one-pot reaction, tetrabutylammonium hydroxide was the best base, and the addition of molecular sieves 13X also promoted the reaction.
- Kutsumura, Noriki,Inagaki, Mai,Kiriseko, Akito,Saito, Takao
-
p. 1844 - 1850
(2015/06/30)
-
- Synthesis of cyclic alkenylsiloxanes by semihydrogenation: A stereospecific route to (Z)-alkenyl polyenes
-
Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes - a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama-Denmark coupling to give (Z)-alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free conditions, whilst their six-membered homologues do not, enabling orthogonality within this structural motif.
- Elbert, Bryony L.,Lim, Diane S. W.,Gudmundsson, Haraldur G.,O'Hanlon, Jack A.,Anderson, Edward A.
-
supporting information
p. 8594 - 8598
(2014/07/21)
-
- Facile One-Pot Synthesis of 1,2,3-Triazoles Featuring Oxygen, Nitrogen, and Sulfur Functionalized Pendant Arms
-
A practical and efficient one-pot synthesis of novel 1,2,3-triazoles featuring nitrogen, oxygen, and sulfur functionalized pendant arms has been developed. The click reaction of mono-propargyl derivatives supported by aniline, thiophenol, and benzyl alcohol, with sodium azide and p-substituted benzyl halogenides, renders a series of N-substituted-1,2,3-triazoles in good yields under mild reaction conditions. The catalyst system was based in Cu(OAc)2·H2O, sodium L-ascorbate, and 1,10-phenanthroline monohydrate, and all reactions were performed in a mixture H2O-ethanol (4:1 v/v). Additionally, the preparation of bis-1,2,3-triazoles supported by di-propargylated aniline was carried out, demonstrating the versatility of the present methodology. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Mendoza-Espinosa, Daniel,Negron-Silva, Guillermo,Lomas-Romero, Leticia,Gutierrez-Carrillo, Atilano,Santillan, Rosa
-
p. 807 - 817
(2014/03/21)
-
- A mild CuI-catalyzed Glaser-type homo-coupling reaction using α,α-dibromo-β-dicarbonyl compounds as oxidants
-
Exploration of α,α-dibromo-β-dicarbonyl compounds as novel organic oxidants for the mild Cu(I)-catalyzed Glaser-type homo-coupling reaction has been achieved, which provides an alternatively efficient pathway for the construction of 1,3-conjugated structures. In addition, the mechanism of this reaction was investigated.
- Fan, Xiaohui,Li, Na,Shen, Tong,Cui, Xiao-Meng,Lv, Hao,Zhu, Hong-Bo,Guan, Yong-Hong
-
supporting information
p. 256 - 261
(2014/01/06)
-
- Palladium-catalyzed intermolecular aminoacetoxylation of alkenes and the influence of PhI(OAc)2 on aminopalladation stereoselectivity
-
A modified protocol has been identified for Pd-catalyzed intermolecular aminoacetoxylation of terminal and internal alkenes that enables the alkene to be used as the limiting reagent. The results prompt a reassessment of the stereochemical course of these reactions. X-ray crystallographic characterization of two of the products, together with isotopic labeling studies, show that the amidopalladation step switches from a cis-selective process under aerobic conditions to a trans-selective process in the presence of diacetoxyiodobenzene.
- Martinez, Claudio,Wu, Yichen,Weinstein, Adam B.,Stahl, Shannon S.,Liu, Guosheng,Muniz, Kilian
-
p. 6309 - 6315
(2013/07/26)
-
- Copper-catalysed multicomponent click synthesis of 5-alkynyl 1,2,3-triazoles under ambient conditions
-
Copper(I) oxide has been found to effectively catalyse the multicomponent click synthesis of fully substituted 5-alkynyl 1,2,3-triazoles from organic halides, sodium azide, and terminal alkynes in methanol under ambient conditions. Georg Thieme Verlag Stu
- Alonso, Francisco,Moglie, Yanina,Radivoy, Gabriel,Yus, Miguel
-
supporting information
p. 2179 - 2182
(2012/11/07)
-
- Structure based drug design, synthesis and evaluation of 4-(benzyloxy)-1-phenylbut-2-yn-1-ol derivatives as 5-lipoxygenase inhibitors
-
A group of 4-(benzyloxy)-1-phenylbut-2-yn-1-ol derivatives were designed using Site point connection method, synthesized and evaluated for their 5-Lipoxygenase (5-LOX) inhibitory activity. Hydrophobic site points in 5-LOX were considered for the study and substitutions were planned such that 4k will have strong hydrophobic group in the corresponding site point. Biological results supported the in silico prediction with compound 4k exhibiting good inhibition with IC50 value of 8 μM against 5-LOX. The compounds 4j and 4k showed potent cytotoxic effects against various cancer cell lines (COLO-205, MDA-MB-231 and HepG2) but with no effect on normal cell line (HaCaT). The overall trend showed 4k as the most potent compound. Further studies demonstrated the protective effect of 4k in mouse Acute Lung Injury (ALI) model induced by lipopolysaccharide (LPS).
- Reddy, Nimmanapalli P.,Chandramohan Reddy,Aparoy, Polamarasetty,Achari, Chandrani,Sridhar, P. Ramu,Reddanna, Pallu
-
experimental part
p. 351 - 359
(2012/02/15)
-
- Triflic acid catalyzed reductive coupling reactions of carbonyl compounds with O-, S-, and N-nucleophiles
-
Highly efficient metal-free reductive coupling reactions of aldehydes and ketones with a range of nucleophiles in the presence of triflic acid (1-5 mol %) as the catalyst are presented. The reactions can be performed at ambient temperature without exclusion of moisture or air. A range of symmetrical and unsymmetrical ethers were obtained by this method in high yields and short reaction times. For the first time, the influence of additional functionalization has been studied. Furthermore, the formation of thioethers from ketones (by addition of unmodified thiols) and of sulfonamides from either aldehydes or ketones has been achieved under catalytic conditions.
- Gellert, Beate A.,Kahlcke, Nils,Feurer, Markus,Roth, Stefanie
-
supporting information; experimental part
p. 12203 - 12209
(2011/11/07)
-
- A regio- and diastereoselective platinum-catalyzed tandem [2+1]/[3+2] cycloaddition sequence
-
Platinum complexes bearing phosphinous acids have efficiently promoted a tandem intermolecular sequence of [2+1]/[3+2] cycloaddition reactions. This process gave access to novel tricyclic systems and the cascade reactions were regio- and diastereoselective (see scheme; Cy=cyclohexyl). The [3+2] cycloaddition reaction was investigated further and two different alkyne partners were used. Copyright
- Achard, Thierry,Lepronier, Aymeric,Gimbert, Yves,Clavier, Herve,Giordano, Laurent,Tenaglia, Alphonse,Buono, Gerard
-
supporting information; experimental part
p. 3552 - 3556
(2011/06/09)
-
- Gold(i)-catalyzed rearrangement of aryl alkynylaziridines to spiro[isochroman-4,2′-pyrrolines]
-
Alkynylaziridines carrying an aryl group could be efficiently converted to spiro[isochroman-4,2′-pyrrolines] with gold salts as catalysts. This new rearrangement involved a Friedel-Crafts type intramolecular reaction followed by cyclization of the aminoallene intermediate, both initiated by the dual σ and π Lewis acidities of gold.
- Kern, Nicolas,Blanc, Aurelien,Weibel, Jean-Marc,Pale, Patrick
-
supporting information; experimental part
p. 6665 - 6667
(2011/06/25)
-
- NHC-catalyzed oxidative cyclization reactions of 2-alkynylbenzaldehydes under aerobic conditions: Synthesis of O-Heterocycles
-
Chemical equations presented. An NHC-catalyzed, regio- and stereoselective oxidative cyclization of o-alkynylbenzaldehydes bearing an unactivated alkyne moiety as an internal electrophile has been developed to afford phthalides and isocoumarins. A single organocatalytic system enabled two sequential C-O bond formations to take place in an atom economical manner via highly efficient dual activation. Molecular oxygen in air could be utilized as a source of an oxygen atom for the oxidation of aldehydes to the corresponding benzoic acids under our newly developed reagent system.
- Park, Jong Hyub,Bhilare, Sachin V.,Youn, So Won
-
supporting information; experimental part
p. 2228 - 2231
(2011/07/09)
-
- Improved synthesis of three methyl-branched pheromone components produced by the female lichen moth
-
Female moths of Lyclene dharma dharma (Arctiidae, Lithosiinae) produce a novel sex pheromone composed of three methyl-branched ketones: 6-methyl-2-octade-canone (I), 14-methyl-2-octadecanone (II), and 6,14-dimethyl-2-octadecanone (III). Their structures were confirmed by syntheses accomplished by a different route for each component. In order to obtain a sufficient amount of the synthetic pheromone, we developed new routes via methyl-branched 1-alkenes: 6-methyl-l-octa-decene (1), 14-methyl-l-octadecene (2), and 6,14-di-methyl-1-octadecene (3). Compound 1 was synthesized by coupling between a C10-chain bromide and a 3-methyl-branched C8 unit (A) prepared from 3-methyl-1,5-pentanediol, 2, by coupling between a C 11-chain bromide and a 3-methyl-branched C7 unit (B) prepared from 2-hexanone, and 3, by connecting A and B, using propargyl alcohol as a C3 linchpin. The use of 3-chloro-1-propanol and tert-butyl acetoacetate as the linchpin was also examined to connect the two synthetic blocks in the synthesis of 3. Components I-III were obtained by Wacker oxidation of the corresponding 1-alkenes 1-3 in good yields.
- Taguri, Tomonori,Yamakawa, Rei,Adachi, Yasushi,Mori, Kenji,Ando, Tetsu
-
experimental part
p. 119 - 124
(2010/04/26)
-
- A gallium-catalyzed cycloisomerization/Friedel-Crafts tandem
-
Under noble (Au, Pt, Ru) and group 13 (Ga, In) metals catalysis, 1,6-arenynes rearrange to give 1,2-dihydronaphthalenes in a high yielding, regiocontrolled fashion. When the reaction is carried out in the presence of electron-rich arenes (anisole, phenol, indole derivatives), Friedel-Crafts addition may follow the cycloisomerization step. Only GaX3 salts proved able to catalyze these two C-C bond formation events. This specificity of gallium has been exploited for the synthesis of valuable polycyclic compounds that would be very difficult to prepare otherwise. For instance, tetrahydroisoquinolines and tetrahydrobenzoazepines have been obtained by selective 6-exo-dig or 7-endo-dig cyclization of N-tethered 1,6-arenynes. DFT calculations were carried out to shed light on the mechanism and provide a rationale for this regiodivergency. Computations also reveal the fundamental role of the tether in the stabilization of carbocationic species. Differential reactivities of other types of substrates in gallium- and gold-catalyzed cascades are also exposed, showing that the two approaches are complementary. In particular, bimolecular Friedel-Crafts additions are facilitated under gallium catalysis.
- Li, Hui-Jing,Guillot, Regis,Gandon, Vincent
-
supporting information; experimental part
p. 8435 - 8449
(2011/03/19)
-
- Diastereoselective synthesis of 2,3,4,5,6-pentafluoroheptanes
-
(Chemical Equation Presented) A stereocontrolled synthesis of alkanes containing five contiguous fluorine atoms is presented. The compounds were prepared by sequential fluorination of diastereoisomeric alcohol-diepoxides. The chemistry involved epoxide ri
- Farran, Daniel,Slawin, Alexandra M. Z.,Kirsch, Peer,O'Hagan, David
-
supporting information; experimental part
p. 7168 - 7171
(2009/12/09)
-