- Traceless Release of Alcohols Using Thiol-Sensitive Oxanorbornadiene Linkers
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A class of ester-amide oxanorbornadiene (EA-OND) molecules was developed to release alcohol cargos by succinimide formation upon addition of a thiol reagent. The resulting ring-closed adducts undergo further fragmentation by retro-Diels-Alder reaction to release a furan moiety in a manner similar to oxanorbornadiene diesters. The rates of each of these fragmentation pathways in the same medium were found to be sensitive to the steric nature of the amide substituent. Alcohol release was much faster in protic solvents than in aprotic ones, suggesting that this system may be useful for rapid response to thiols in biological environments. Accordingly, the attachment and thiol-dependent release of cholesterol was characterized as an example of the manipulation of a drug-like cargo.
- Aioub, Allison G.,Higginson, Cody J.,Finn
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- A novel fragmentation of 7-azabicyclo[2.2.1]hepta-2,5-dienes: Synthesis of cis-5-amidino-pyrrolidine-2-acetic acid derivatives
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A new fragmentation reaction of 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene carboxylic esters with 2-amino or 2-aminomethyl anilines is described. It leads to cis-5-(benzimidazol-2-yl)- or cis-5-(3,4-dihydroquinazolin-2-yl)-pyrroline-2- acetic acid esters.
- Weber, Dirk,Heller, Eberhard,Hoenke, Christoph,Hoerer, Stefan,Baeuerle, Peter,Austel, Volkhard
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- Synthesis and characterization of a new two photon excitable acid sphingomyelinase FRET probe
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Recently, FRET probes for acid sphingomyelinase (ASM) have enabled the observation of enzyme activity in intact cells for the first time. Here we present an ASM FRET probe specifically optimized for 2-photon excitation. To facilitate probe characterization and comparison to the previous probe, we mixed the two intact probes with defined amounts of the probes' ceramide cleavage products and mounted them on lipid beads. Directly excited NBD FRET acceptor fluorescene proved to be a useful means of reference and showed that the new probe is brighter, albeit only moderately, than the previous one. The new probe was then used to detect inhibition by various ASM inhibitors microscopically for the first time. Also in cells, directly excited acceptor fluorescence proved to be a useful parameter in addition to FRET to visualize inhibition of ASM.
- Mohamed, Zain H.,Rhein, Cosima,Schmid, Benjamin,Tripal, Philipp,Kornhuber, Johannes,Arenz, Christoph
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Read Online
- Synthesis and evaluation of D-thioluciferin, a bioluminescent 6'-thio analog of Dluciferin
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All known light-emitting firefly-bioluminescent luciferin analogs are either derived from the 6'-hydroxy- and/or 6'-aminoluciferin. We report the synthesis of D-thioluciferin, a 6'-thio analog or isostere of D-luciferin, starting from p-aminothiophenol, using a unique thioacrylate-S-protecting-group strategy. Upon treatment of Dthioluciferin with purified Photinus pyralis (Ppy) luciferase (Luc), a bioluminescence emission with a red-shift λmax relative to D-luciferin was observed. It was also shown that disulphide and sulphide analogs of Dthioluciferin did not produce similar bioluminescences relative to D-thioluciferin when treated with Ppy Luc under standard conditions, thus, providing a foundation for the development of D-thioluciferin based probes based on disulphide reduction and S-dealkylation.
- Rylands, Marwaan,Jardine, Anwar
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p. 176 - 189
(2021/03/17)
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- Asymmetric synthesis of dihydrocarbazoles through a Friedel-Crafts alkylation/annulation sequential reaction of indoles
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An enantioselective tandem Friedel-Crafts alkylation/annulation of indoles with diazoacetoacetate enones is realized in one pot. A series of dihydrocarbazoles were obtained in moderate yields with good to excellent ee values by using a RhII/ScIII dual-metallic catalyst system. Control experiments revealed that ScIII is critical to both the alkylation and annulation.
- Hu, Linfeng,Cao, Weidi,Wang, Kaixuan,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 13138 - 13141
(2021/12/16)
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- Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n) and [1-14C]-CA (PEG)n via oxa-Michael addition of amino-polyethylene glycols to propiolates vs to acrylates
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Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n) via oxa-Michael addition of amino-polyethylene glycols to either acrylates or propiolates was investigated. Compared with the oxa-Michael addition to acrylates, the corresponding addition to propiolates was found to proceed under mild reaction conditions and afford the adducts in high yields from a broad scope of substrates. A two-step efficient and convenient synthesis of benzyl [1-14C]-propiolate from 14CO2 was therefore developed and utilized as a common synthon to afford practical and high yielding access to [1-14C]-CA (PEG)n.
- Song, Fengbin,Chen, Lu,Lin, Ronghui,Salter, Rhys
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- Solvent-free and montmorillonite K10-catalyzed domino reactions for the synthesis of pyrazoles with alkynylester as a dual synthon
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A highly regioselective, solvent-free and montmorillonite K10 clay-catalyzed domino process with an unprecedented ring-closing C-C bond-formation reaction is described for the synthesis of a new class of 1,3,4-trisubstituted and 1,4-disubstituted pyrazole
- Annes, Sesuraj Babiola,Ramesh, Subburethinam,Saritha, Rajendhiran,Shankar, Bhaskaran,Subramanian, Saravanan
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supporting information
p. 2388 - 2393
(2020/05/13)
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- Cyclopropanation of active methylene compounds with β-alkoxycarbonyl vinylsulfonium salts
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An efficient synthesis of β-alkoxycarbonyl vinylsulfonium salts had been developed. Their reaction with indene-1,3-diones and other active methylene compounds provided cyclopropane carboxylates in good yields. A tentative reaction mechanism was proposed.
- Guo, Shenquan,Zhang, Niuniu,Tang, Xiangzheng,Mao, Zhifeng,Zhang, Xuejing,Yan, Ming,Xuan, Yining
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supporting information
p. 406 - 408
(2018/09/25)
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- DERIVATIVES OF LUCIFERIN AND METHODS FOR THEIR SYNTHESIS
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6-Thio derivatives of D-luciferin, also referred to as D-thioluciferins, having the general structure of Formula (I) are provided. Methods for synthesising D-luciferin, its derivatives, and their related 2-cyanobenzothiazole precursors are also provided. These compounds are commercially valuable due to their application in optical imaging, particularly in bioluminescence imaging.
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Page/Page column 31
(2019/02/13)
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- Silica Gel as a Promoter of Sequential Aza-Michael/Michael Reactions of Amines and Propiolic Esters: Solvent- and Metal-Free Synthesis of Polyfunctionalized Conjugated Dienes
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We present an efficient, simple, metal- and solvent-free silica-gel-promoted synthesis of functionalized conjugated dienes by sequential aza-Michael/Michael reactions by starting from commercially available primary amines and propiolic esters. The scope a
- Aleksi?, Jovana,Stojanovi?, Milovan,Baranac-Stojanovi?, Marija
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p. 1811 - 1835
(2018/07/29)
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- Palladium-Catalyzed Regio- and Stereoselective Coupling-Addition of Propiolates with Arylsulfonyl Hydrazides: A Pattern for Difunctionalization of Alkynes
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A new pattern for difunctionalization of alkynes via a palladium-catalyzed regio- and stereoselective coupling-addition of propiolates with arylsulfonyl hydrazides is disclosed. The approach enables the synthesis of various highly functionalized (E)-vinylsulfones in satisfactory yields. Arylsulfonyl hydrazides act as both aryl and sulfonyl sources via selective cleavage of Ar(C)-S and S-N bonds, which are simultaneously incorporated onto the terminal carbon atom of an alkyne molecule.
- Liu, Lixin,Sun, Kang,Su, Lebin,Dong, Jianyu,Cheng, Lei,Zhu, Xiaodong,Au, Chak-Tong,Zhou, Yongbo,Yin, Shuang-Feng
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supporting information
p. 4023 - 4027
(2018/07/15)
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- Direct spirocyclization from keto-sulfonamides: An approach to azaspiro compounds
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Spontaneous spirocyclization of keto-sulfonamides via ynamides through a one-pot process is presented. Push-pull ynamides were obtained through Michael addition/elimination without Cu. The obtained azaspiro compounds are building blocks for indole alkaloids. Theoretical studies provide insights into the mechanism of the formal Conia-ene reaction.
- Beltran, Frédéric,Fabre, Indira,Ciofini, Ilaria,Miesch, Laurence
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supporting information
p. 5042 - 5045
(2017/11/06)
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- Copper-Catalyzed Enantioselective Synthesis of β-Boron β-Amino Esters
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In this report, the enantioselective, copper-catalyzed borylation of β-amidoacrylates is disclosed. A broad variety of biologically important α-aminoboronates has been prepared with consistently high levels of enantiocontrol using an inexpensive copper catalyst and a commercially available chiral ligand. The method can be applied to the synthesis of novel boron-containing dipeptides and hemiboronates.
- López, Aurora,Clark, Timothy B.,Parra, Alejandro,Tortosa, Mariola
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supporting information
p. 6272 - 6275
(2017/12/08)
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- New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology
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A series of new colchicinoids with a variable triazole unit at C-7 was synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (click-chemistry) of a colchicine-derived azide with various alkynes and the cytotoxicity against THP-1 and Jurkat cancer cell lines was used for structural optimization. Three particularly active compounds (IC50 ≤ 5 nM) were additionally investigated with respect to their efficacy against relevant solid tumor cell lines (HeLa, A549, and SK MES 1). Besides distorting the microtubule morphology by tubulin depolymerization, one compound also exhibited a pronounced centrosome declustering effect in triple negative breast cancer cells (MDA-MB-231) and nonsmall cell lung cancer cells (H1975).
- Thomopoulou, Persefoni,Sachs, Julia,Teusch, Nicole,Mariappan, Aruljothi,Gopalakrishnan, Jay,Schmalz, Hans-Günther
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supporting information
p. 188 - 191
(2016/03/01)
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- Palladium-catalyzed intermolecular [3 + 2] carbocyclization of alkynols and propiolates: An efficient entry to halo-cyclopentadienes
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A novel and efficient Pd-catalyzed intermolecular [3 + 2] carbocyclization of alkynols and electron-deficient alkynes for the synthesis of halo-cyclopentadienes (Cps) has been developed. The present protocol employs simple propargyl alcohols as the C3 group to participate in the cyclization reaction, providing a highly convenient and atom-economical entry to the halo-cyclopentadiene framework. The Royal Society of Chemistry.
- Gao, Yang,Wu, Wanqing,Huang, Huawen,Huang, Yubing,Jiang, Huanfeng
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supporting information
p. 846 - 848
(2014/01/06)
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- Investigation of the lipase-catalysed reaction of aliphatic amines with ethyl propiolate as a route to N-substituted propiolamides
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The lipase-catalysed reaction of aliphatic amine with ethyl propiolate was investigated using benzylamine as reference amine. The conditions were optimised to favour the 1,2-addition, i.e., formation of N-benzylprop-2-ynamide, versus the 1,4-addition. Immobilised Candida antarctica lipase (CALB) was found to be the most efficient enzyme, and the reactions were performed in solvents, such as tBME, dioxane or toluene. The methods were used to prepare propiolamides from aliphatic amines in good to excellent yields. The reactivity of O- and S-nucleophiles was compared in the same conditions.
- Bonte, Simon,Ghinea, Ioana Otilia,Baussanne, Isabelle,Xuereb, Jean-Paul,Dinica, Rodica,Demeunynck, Martine
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p. 5495 - 5500
(2013/07/05)
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- First- and second-generation practical syntheses of chroman-4-one derivative: A key intermediate for the preparation of SERT/5-HT1A dual inhibitors
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Two approaches to large-scale synthesis of the key intermediate 9, a precursor of novel dual inhibitors of SERT/5-HT1A receptor, are described. These two approaches each feature a mild and efficient method for construction of the chroman-4-one
- Nishida, Tomoaki,Yoshinaga, Hidefumi,Toyoda, Tomohiro,Toshima, Minoru
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experimental part
p. 625 - 634
(2012/07/03)
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- Phosphine/palladium-catalyzed syntheses of alkylidene phthalans, 3-deoxyisoochracinic acid, isoochracinic acid, and isoochracinol
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In this study we used sequential catalysis-PPh3-catalyzed nucleophilic addition followed by Pd(0)-catalyzed Heck cyclization-to construct complex functionalized alkylidene phthalans rapidly, in high yields, and with good stereoselectivities (E/Z ratios of up to 1:22). The scope of this Michael-Heck reaction includes substrates bearing various substituents around the alkylidene phthalan backbone. Applying this efficient sequential catalysis, we accomplished concise total syntheses of 3-deoxyisoochacinic acid, isoochracinic acid, and isoochracinol.
- Fan, Yi Chiao,Kwon, Ohyun
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supporting information; experimental part
p. 3264 - 3267
(2012/08/28)
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- Investigation of Synthetic Routes to a Key Benzopyran Intermediate of a 5HT4 Agonist
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The supply route to GlaxoSmithKline's 5HT4 receptor agonist 1 centred on the construction of key benzopyran fragment 2. Our attempts to define the final manufacturing route for this component are described through a series of disconnections. The systematic approach undertaken towards the construction of the benzopyran skeleton focused on cycli- sation strategies from appropriate precursors and evaluation of the performance of the key steps.
- Rassias, Geracimos,Stevenson, Neil G.,Curtis, Neil R.,Northall, John M.,Gray, Matthew,Prodger, Jeremy C.,Walker, Andrew J.
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scheme or table
p. 92 - 98
(2010/04/28)
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- Improved and scalable synthetic route to the synthon 17-β-(2- Carboxyethyl)-1,3,5(10)-estratriene: An important intermediate in the synthesis of bone-targeting estrogens
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An improved, highly scalable methodology for the multigram-scale preparation of an important synthon, 17-β-(2-carboxyethyl)-1,3,5(10)- estratriene, is described. Previous approaches have failed to provide useful quantities of the analytically pure product because of facile retro-Michael breakdown of the-alkoxy carbonyl precursors during workup and isolation operations. The synthetic approach described herein has been designed specifically to sidestep this problematic breakdown process. This new scalable method of preparation overcomes a major hurdle in the exploration of structure-activity relationships centered around novel estradiol derivatives with bone-targeting properties and also provides a scalable process for subsequent developmental work.
- Nasim, Shama,Vartak, Ashish P.,Pierce, William M.,Grant Taylor,Crooks, Peter A.
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scheme or table
p. 772 - 781
(2011/03/20)
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- HYDROXYMETHYL PYRROLIDINES AS BETA 3 ADRENERGIC RECEPTOR AGONISTS
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The present invention provides compounds of Formula I, pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.
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Page/Page column 59-60
(2009/10/30)
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- HYDROXYMETHYL PYRROLIDINES AS BETA 3 ADRENERGIC RECEPTOR AGONISTS
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The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.
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Page/Page column 48
(2009/10/17)
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- The reaction of 2-(tetrazol-5-yl)alkyl ketones and of 2-(tetrazol-5-yl)alkanoic acid derivatives with lead tetraacetate. A novel method of preparation of alk-2-ynyl ketones and alk-2-ynoic acid derivatives
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The majority of tetrazolylacetyl derivatives 2 and 7, when treated with lead tetraacetate in dry 1,4-dioxane at room or lower temperature, are oxidized with elimination of molecular nitrogen mainly to the corresponding alkynoyl derivatives 4 and 8, respectively. Vinylidenes (25) have been shown to be the intermediates of the reaction. The reaction does not take place when either the tetrazolyl group is N-substituted or the carbon atom separating the tetrazolyl and the carbonyl groups is disubstituted or these two groups are separated by two carbon atoms as in compound 17. The reaction offers a convenient method for the conversion of 2-cyanoacetyl derivatives into alk-2-ynoyl derivatives via intermediate tetrazolylacetyl derivatives. The 4-methoxyanilide 7o reacts differently, affording the fused heterocyclic compounds 19o and 20o.
- Fetter,Nagy,Giang,Kajtar-Peredy,Rockenbauer,Korecz,Czira
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p. 1131 - 1139
(2007/10/03)
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- Lithium bis-(diisopropylamino)boracetylide [LiC≡C-B(ni-Pr2)2]. A new reagent for the preparation of terminal alkynes
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Terminal alkynes RC≡CH [R = PhCO, PhCH2OCO, (CH3)2CHCH2OCO. Et2NCO. (EtO)2P(O), PhCH2, H2C=CH-CH2, and Ph-CH(OH)-] may be prepared in satisfactory yield in a one-pot process by reaction in THF at -78°C of the titled reagent with electrophiles followed by acidic workup with dilute HCl.
- Blanchard, Christiane,Vaultier, Michel,Mortier, Jacques
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p. 8863 - 8866
(2007/10/03)
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- CCK ANALOGS WITH APPETITE REGULATING ACTIVITY
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The invention is directed to novel CCK analogs wherein Tryptophan and/or Phenylalamine are substituted with a radical which provides enhanced appetite suppressant activity to the peptide.
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- IMPROVED PREPARATION OF ALIPHATIC PROPYNOIC ESTERS
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An improved procedure of esterification of propynoic acid, based on the N,N'-dicyclohexylcarbodiimide 4-dimethylaminopyridine condensation, is presented, which gives good results with primary, secondary, allylic and homoallylic alcohols.Reactions conditions are mild.Some limitations are given.
- Balas, L.,Jousseaume, B.,Langwost, B.
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p. 4525 - 4526
(2007/10/02)
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- Regioselectivity in cycloaddition reactions on solid phases
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A 1percent crosslinked divinylbenzene-styrene copolymer, incorporating benzyl acrylate groups, reacted in normal Diels-Alder reactions with E-1-phenyl-1,3-butadiene or methyl E-2,4-pentadienoate to give their respective polymer-bound benzyl cyclohexenecarboxylates.Polymer-bound benzyl propiolate and polymer-bound benzyl phenylpropiolate reacted with benzonitrile oxide in a typical 1,3-dipolar addition reaction to give their respective polymer-bound isoxazoles.Cleavage of the polymer-bound Diels-Alder adducts and the polymer-bound 1,3-dipolar addition adduct derived from polymer-bound benzyl propiolate gave mixtures of ortho and meta regiomers similar to those produced in analogous reactions in solution.Cleavage of the polymer-bound 1,3-dipolar addition adduct, derived from polymer-bound benzyl phenylpropiolate, followed by esterification, gave a solitary adduct, 4-carbomethoxy-3,5-diphenylisoxazole, but an analogous solution 1,3-dipolar addition yielded a 1:1 ratio of the two possible regiomers.
- Yedidia, Varda,Leznoff, Clifford C.
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p. 1144 - 1150
(2007/10/02)
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