- Asymmetric ammonium ylid rearrangements: the effect of nitrogen asymmetry
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[2,3]-Sigmatropic rearrangements of allylic ammonium ylids derived from glycinoylcamphorsultams are highly selective in terms of relative and absolute stereocontrol only when acyclic alkenes are present. When chiral esters of ylids derived from N-methyltetrahydropyridine ('NMTP') undergo rearrangement, the reactions show exclusive cis-stereoselectivity but the products are obtained with virtually no absolute stereocontrol. These observations support the notion that sigmatropic rearrangements of N-chiral ammonium ylids are controlled by nitrogen stereogenicity.
- Sweeney,Tavassoli, Ali,Workman, James A.
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Read Online
- Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
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α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
- Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
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supporting information
p. 15413 - 15419
(2021/09/30)
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- Stereoselective synthesis of oxazolidin-2-ones via an asymmetric aldol/curtius reaction: Concise total synthesis of (?)-cytoxazone
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Herein, we are reporting an efficient approach toward the synthesis of 4,5-disubstituted oxazolidin-2-one scaffolds. The developed approach is based on a combination of an asymmetric aldol and a modified Curtius protocol, which uses an effective intramolecular ring closure to rapidly access a range of oxazolidin-2-one building blocks. This strategy also permits a straightforward and concise asymmetric total synthesis of (?)-cytoxazone. Consisting of three steps, this is one of the shortest syntheses reported to date. Ultimately, this convenient platform would provide a promising method for the early phases of drug discovery.
- Choi, Hosam,Choi, Joohee,Jang, Hanho,Lee, Kiyoun
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- Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions
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Oxidative alkene difunctionalization reactions are important in synthetic organic chemistry because they can install polar functional groups onto simple non-polar alkene moieties. Many of the most common methods for these reactions rely upon the reactivity of pre-oxidized electrophilic heteroatom donors that can often be unstable, explosive, or difficult to handle. Herein, we describe a method for alkene oxyamination and diamination that utilizes simple carbamate and urea groups as nucleophilic heteroatom donors. This method uses a tandem copper–photoredox catalyst system that is operationally convenient. The identity of the terminal oxidant is critical in these studies. Ag(I) salts proved to be unique in their ability to turn over the copper cocatalyst without deleteriously impacting the reactivity of the organoradical intermediates.
- Reed, Nicholas L.,Herman, Madeline I.,Miltchev, Vladimir P.,Yoon, Tehshik P.
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supporting information
p. 351 - 356
(2019/02/20)
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- A new type of L-Tertiary leucine-derived ligand: Synthesis and application in Cu(II)-catalyzed asymmetric Henry reactions
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A new series of Schiff bases derived from amino acids were developed as chiral ligands for Cu(II)-catalyzed asymmetric Henry reactions. The optimum ligand 7d exhibited outstanding catalytic efficiency in the Cu(II)-catalyzed asymmetric Henry additions of four nitroalkanes to different kinds of aldehydes to produce 76 desired adducts in high yields (up to 96%) with excellent enantioselectivities, up to 99% enantiomeric excess (ee).
- Cai, Zedong,Lan, Ting,Ma, Pengfei,Zhang, Jingfang,Yang, Qingqing,He, Wei
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- Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions
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Secondary 1,3,2-diazaphospholenes have a polarized P?H bond and are emerging as molecular hydrides. Herein, a class of chiral, conformationally restricted methoxy-1,3,2-diazaphospholene catalysts is reported. We demonstrate their catalytic potential in asymmetric 1,4-reductions of α,β-unsaturated carbonyl derivatives, including enones, acyl pyrroles, and amides, which proceeded in enantioselectivities of up to 95.5:4.5 e.r.
- Miaskiewicz, Solène,Reed, John H.,Donets, Pavel A.,Oliveira, Caio C.,Cramer, Nicolai
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supporting information
p. 4039 - 4042
(2018/03/13)
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- Kinetic resolution of racemic amino alcohols through intermolecular acetalization catalyzed by a chiral Bronsted acid
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The kinetic resolution of racemic secondary alcohols is a fundamental method for obtaining enantiomerically enriched alcohols. Compared to esterification, which is a well-established method for this purpose, kinetic resolution through enantioselective intermolecular acetalization has not been reported to date despite the fact that the formation of acetals is widely adopted to protect hydroxy groups. By taking advantage of the thermodynamics of acetalization by the addition of alcohols to enol ethers, a highly efficient kinetic resolution of racemic amino alcohols was achieved for the first time and in a practical manner using a chiral phosphoric acid catalyst.
- Yamanaka, Takuto,Kondoh, Azusa,Terada, Masahiro
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p. 1048 - 1051
(2015/02/19)
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- Enantioselective synthesis of dihydro-1 H -benzindoles
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The first examples of dihydro-1H-benzindoles by enantioselective γ-lactamization reaction of naphthyl sulfilimines with trichloroacetyl chloride in the presence of ZnCu as catalyst (≥98:2 er and 65-80% yields) are described. Products are obtained by [3,3]-sigmatropic rearrangement of the azasulfonium enolate or followed by a second allylic rearrangement that transfers chirality. The absolute stereochemistry was confirmed by X-ray crystallography, which provides support for the mechanisms proposed.
- Silveira, Gustavo P.,Marino, Joseph P.
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p. 3379 - 3383
(2013/06/26)
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- Open tubular molecular imprinted polymer fabricated in silica capillary for the chiral recognition of neutral enantiomers in capillary electrochromatography
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In this study, we have expanded the applicability of the pre-established generalized preparation protocol to MIPs with a neutral template. The (4S,5R)-4-methyl-5-phenyl-2-oxazolidinone MIP layer was formed inside a pretreated and silanized fused silica capillary, and its chiral separation performance was examined. Optimization of chiral separation was also carried out. This is the very first report of somewhat successful application of the generalized preparation protocol to a MIP with a genuine neutral template. Copyright
- Yang, Song Hee,Zaidi, Shabi Abbas,Cheong, Won Jo,ALOthman, Zeid A.,ALMajid, Abdullah M.
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scheme or table
p. 1664 - 1668
(2012/07/13)
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- A ring-closing metathesis-based approach to the synthesis of (+)-tetrabenazine
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A modular stereoselective synthesis of the vesicular monoamine transport inhibitors (+)-tetrabenazine ((+)-1) and (+)-α-dihydrotetrabenazine ((+)-2) has been developed. The approach is based on amine 4 and acid 5 as the key building blocks, which were elaborated into macrolactam 3 by amide coupling and a subsequent highly E-selective RCM reaction. Macrolactam 3 could be converted into tetrabenazine in three known steps.
- Johannes, Manuel,Altmann, Karl-Heinz
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supporting information; experimental part
p. 3752 - 3755
(2012/09/07)
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- Synthesis of cyanoacetyl oxazolidinones
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Carefully controlled displacement of chiral chloroacetyl imides with cyanide afforded previously unreported cyanoacetimides in good overall yield. Knoevenagel condensation of the cyanoacetimides to furnish acrylonitriles was also demonstrated. Georg Thiem
- Weeber, Kaitlyn M.,Schwarz, Jacob B.
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experimental part
p. 1993 - 1996
(2012/09/07)
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- Chemical development of an α2δ ligand, (3 S,5 R)-3-(Aminomethyl)-5-methyloctanoic acid
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Three synthetic approaches, suitable for the large scale manufacture of the α2δ-ligand, (3S,5R)-3-(aminomethyl)-5-methyloctanoic acid 3, have been evaluated. The selected seven step manufacturing process has then been optimized and used to deliver over 20 kg of API; salient features of the synthesis include the use of 4,4,4-trimethoxybutyronitrile as an efficient four carbon amino acid equivalent. Highly selective kinetic resolution of the C3 stereocentre was accomplished via diastereoselective hydrolysis of a cyanoester intermediate using Amano Lipase PS-SD. Extensive process optimisation of the route starting from (R)-2-methylpentanol, led to significant improvements through telescoping, with less than 62 kg of solvent being needed to produce 1 kg of API.
- Murtagh, Lorraine,Dunne, Catherine,Gabellone, Gino,Panesar, Niamh J.,Field, Stuart,Reeder, Lisa M.,Saenz, James,Smith, George P.,Kissick, Kyle,Martinez, Carlos,Van Alsten, John G.,Evans, Margaret C.,Franklin, Lloyd C.,Nanninga, Thomas,Wong, John
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experimental part
p. 1315 - 1327
(2012/01/12)
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- Synthesis of 2-Arylethylamines by the Curtius Rearrangement
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2-Arylethylamine derivatives were synthesized using the Curtius reaction and with three different methods of preparing the acyl azide functional group. Carbamates derived from isocyanate were convenient protecting groups for alkylation of amines. Starting from benzaldehyde, amphetamine was prepared in three steps through an oxazolidin-2-one intermediate in 62% overall yield. Copyright Taylor & Francis Group, LLC.
- Schulze, Matthias
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experimental part
p. 1461 - 1476
(2010/07/08)
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- Carbon dioxide as a carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas: Scope and limitations
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Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl2, TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields. This methodology was successfully applied to the synthesis of cyclic ureas up to 7-membered rings from the corresponding diamines.
- Paz, Jairo,Perez-Balado, Carlos,Iglesias, Beatriz,Munoz, Luis
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supporting information; experimental part
p. 3037 - 3046
(2010/07/15)
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- Experimental and DEE study of the conversion of ephedrine derivatives into oxazolidinones. Double SN2 mechanism against SN1 mechanism
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Sulfonation of the N-Boc derivatives of 1,2-aminoalcohols, such as ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, thiomicamine, and chloramphenicol yields a mixture of the corresponding oxazolidinones with inversion (erythro derivatives) and!or retention of configuration (threo derivatives)at C5. We suggest a competition between two mechanisms: an intramolecular SN2 process initiated by attack of the carbonyl oxygen of the Boc group to the benzylic carbon and the other one through a double SN2 process. In the erythro derivatives the first mechanism is predominant, while in the threo derivatives both mechanisms have similar energy. This hypothesis is supported by theoretical calculations and additional experimental assays.
- El Moncef, Abdelkarim,El Hadrami, El Mestafa,González, Miguel A.,Zaballos, Elena,Zaragozá, Ramón J.
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experimental part
p. 5173 - 5184
(2010/08/22)
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- Stereoselective synthesis of a monocyclic peloruside A analogue
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Chemical Equation Presentation The stereoselective synthesis of the monocyclic peloruside A analogue 4 has been achieved, following a new efficient approach for the introduction of the side chain, involving a late-stage addition of vinyl lithium species 7a to aldehyde 8. Further key steps are a highly diastereoselective allyltitanation reaction and a RCM-based macrocyclization.
- Wulischleger, Christoph W.,Gertsch, Juerg,Altmann, Karl-Heinz
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supporting information; experimental part
p. 1120 - 1123
(2010/06/13)
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- Asymmetric synthesis of amlnocyclopropanes and N-cyclopropylamino alcohols through direct amidocyclopropanation of alkenes using chiral organozinc carbenoids
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Chiral N-(diethoxymethyl)oxazolidinones, prepared from the corresponding oxazolidinones by heating in trielhyl orthoformate, can be used as organozinc carbenoid precursors for the direct enantioselective amidocyclopropanation of alkenes. The reaction is successful with a wide range of oxazolidinones and alkenes and proceeds with moderate to excellent yield and stereoselectivity. In most cases the trans/exo amidocyclopropane product, is favoured, although certain cyclic alkenes such as indene favour the formation of the endo cyclopropane. The products can be readily elaborated to produce cyclopropylamino alcohols and amino acids. Wiley-VCH Verlag GmbH & Co. KGaA.
- Begis, Guillaume,Cladingboel, David E.,Jerome, Laure,Motherwell, William B.,Sheppard, Tom D.
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experimental part
p. 1532 - 1548
(2009/09/08)
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- Carbonylation with CO2 and phosphorus electrophiles: A convenient method for the synthesis of 2-oxazolidinones from 1,2-amino alcohols
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2-Oxazolidinones were prepared in good yields from 1,2-amino alcohols and CO2 in the presence of tetramethyl-phenylguanidine (PhTMG) as a base and a variety of phosphorus electrophiles under mild conditions. This procedure is advantageous over previous methodologies and relies on a novel carbonylation procedure that utilizes nontoxic CO2 and phosphorus electrophiles. Georg Thieme Verlag Stuttgart.
- Paz, Jairo,Pérez-Balado, Carlos,Iglesias, Beatriz,Mu?oz, Luis
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body text
p. 395 - 398
(2009/08/09)
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- Hydrogenation of N-acylcarbamates and N-acylsulfonamides catalyzed by a bifunctional [Cp*Ru(PN)] complex
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Awakening of the Cp one: the bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with gtood recovery of the chiral oxazolidinone auxiliary. EWG=electron- withdrawing group.
- Ito, Masato,Koo, Lee Wei,Himizu, Akio,Kobayashi, Chika,Sakaguchi, Ayaka,Ikariya, Takao
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scheme or table
p. 1324 - 1327
(2009/06/30)
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- METHOD OF PREPARING PSEUDONOREPHEDRINE
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A method of making high diastereoselective and enantiomerically pure pseudonorephedrine and the hitherto unknown compound (1R,2R) pseudonorephedrine.
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Page/Page column 4
(2008/06/13)
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- Expeditious, large scale preparation of ethyl (R)-5-methyl-3-oxo octanoate via a cross Claisen reaction between N-acyl oxazolidinone derivatives and the magnesium enolate of potassium ethyl malonate
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A new and efficient method for the direct conversion of N-acyl oxazolidinones to a β-keto ester is disclosed. The one-pot transformation is effected by the utilization of an excess of Lewis acid along with base and potassium ethyl malonate. This methodology has been applied to the large scale preparation of ethyl (R)-5-methyl-3-oxooctanoate.
- Magano, Javier,Nanninga, Thomas N.,Winkle, Derick D.
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p. 2956 - 2959
(2008/09/20)
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- Studies toward the synthesis of pinnatoxins: the spiroimine fragment
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An enantioselective approach to the spiroimine fragment of pinnatoxins is described. The strategy is based on a recently developed diastereoselective Ireland-Claisen rearrangement to establish the challenging congested quaternary and tertiary stereocenters within the cyclohexene ring.
- Stivala, Craig E.,Zakarian, Armen
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p. 6845 - 6848
(2008/02/13)
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- Total synthesis and antitumor activity of ZK-EPO: The first fully synthetic epothilone in clinical development
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Going to trial: From about 350 active epothilone analogues synthesized by a highly convergent synthesis, one (ZK-EPO, see picture) has been chosen for clinical development on the basis of its outstanding preclinical data. This compound exhibits higher activity and efficacy than taxanes (e.g. paclitaxel) and second-generation epothilones, a fast and efficient cellular uptake, no recognition by efflux mechanisms, and an improved therapeutic window. (Chemical Equation Presented)
- Klar, Ulrich,Buchmann, Bernd,Schwede, Wolfgang,Skuballa, Werner,Hoffmann, Jens,Lichtner, Rosemarie B.
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p. 7942 - 7948
(2007/10/03)
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- Asymmetric tandem Michael-Aldol reactions between 3-cinnamoyloxazolidine-2- thiones and aldehydes
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Reactions between chiral 3-cinnamoyl-4-methyl-5-phenyl-1,3-oxazolidine-2- thiones and aromatic aldehydes in the presence of BF3·Et 2O diastereoselectively produced tricyclic compounds incorporating a bridgehead carbon bound to four heteroatoms in high yields. Four stereocenters were induced during the reaction. The tricyclic products were transformed into propane-1,3-diols bearing three consecutive stereocenters by acid hydrolysis, S-methylation, and reductive removal of the chiral auxiliary.
- Kinoshita, Hironori,Osamura, Takashi,Mizuno, Kazumi,Kinoshita, Sayaka,Iwamura, Tatsunori,Watanabe, Shin-Ichi,Kataoka, Tadashi,Muraoka, Osamu,Tanabe, Genzoh
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p. 3896 - 3904
(2008/02/06)
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- Pd(OAc)2-catalyzed carbonylation of amines
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A phosphine-free catalytic system [Pd(OAc)2-Cu(OAc) 2-air] induced a substrate-specific carbonylation of amines in boiling toluene under CO gas (1 atm). Symmetrical N,N′-dialkylureas were obtained by the carbonylation of primary amines. N,N,N′-Trialkylureas were selectively formed by addition of a secondary amine to the above reaction vessel. Secondary amines did not give tetraalkylureas. However, dialkylamines with a phenyl group on their alkyl chains, such as N-monoalkylated benzylic amine or phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In contrast, carbonylation of ω- arylalkylamines with a hydroxyl group gave neither ureas nor benzolactams but instead produced 1,3-oxazolidinones smoothly. Hydrochlorides of amines also underwent carbonylation to afford the corresponding amides under the conditions used. This procedure made it possible to prepare ureas of amino acid esters and N-alkylcarbamates in practical yields.
- Orito, Kazuhiko,Miyazawa, Mamoru,Nakamura, Takatoshi,Horibata, Akiyoshi,Ushito, Harumi,Nagasaki, Hideo,Yuguchi, Motoki,Yamashita, Satoshi,Yamazaki, Tetsuro,Tokuda, Masao
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p. 5951 - 5958
(2007/10/03)
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- 1,3-Heterazolidines-2-heterounsaturated compounds derived from ephedrines
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Herein, a direct and easy method for preparing 2-oxo-, 2-thione- or 2-imine-1,3-heterazolidines derived from ephedrines and norephedrines are reported. The method is based on solvent free heating of ephedrines with oxocyanate or thiocyanate salts (180-200 °C). In the reactions with potassium oxocyanate in refluxing ethanol, it was possible to isolate ureidic derivatives. The structure and stereochemistry of the compounds were determined by 1H, 13C NMR, IR spectroscopies and mass spectrometry. Ureidic derivatives, cis-1,5-dimethyl-4-phenyl-imidazolidine-2-thione and trans-4-methyl-5-phenyl-thiazolidine-2-one are new compounds. Ephedrineurea, cis-1,5-dimethyl-4-phenyl-imidazolidine-2-thione and trans-4-methyl-5-phenyl-thiazolidine-2-one were also studied by X-ray diffraction.
- Cruz, Alejandro,Contreras, Rosalinda,Padilla-Martinez, Itzia I.,Juarez-Juarez, Minerva
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p. 1499 - 1505
(2007/10/03)
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- Remarkably efficient charcoal-promoted ring-closing carbonylations
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An efficient, versatile and practical gram-scale preparation of oxazolidinone, imidazolidinone and dioxolanone is achieved. Georg Thieme Verlag Stuttgart.
- Alouane, Nacira,Boutier, Audrey,Baron, Cyriella,Vrancken, Emmanuel,Mangeney, Pierre
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p. 885 - 889
(2007/10/03)
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- Reactivity difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols
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In reactions of (2,3-anti)-3-amino-1,2-diols with diphosgene and phosgene and their conversion into 1,3-oxazolidin-2-ones, some differences in the stereochemistry of the reactions have been found with these two reagents. The reactions with phosgene afforded the expected cis-oxazolidinones, and in the reaction with diphosgene under the same reaction conditions, the trans-oxazolidinones were also obtained.
- Hamdach,El Hadrami,Gil,Zaragozá,Zaballos-García,Sepúlveda-Arques
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p. 6392 - 6397
(2007/10/03)
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- The preparation and reaction of enolates within micro reactors
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Over the past 5 years, interest in the miniaturisation of chemical synthesis has grown rapidly, however in order to facilitate transfer of the technology from its current position as a research tool to industrial applications, a core understanding of the challenges associated with transferring reactions from the macro to the micro domain is required. This paper therefore aims to broach this problem by investigating the application of micro reactors to a range of commonly employed synthetic reactions including acylation, aldol, alkylation, 1,4-conjugate addition (Michael addition) and the Knoevenagel condensation. Comparison of the results obtained with traditional batch techniques enable us to highlight some of the advantages associated with micro reaction technology.
- Wiles, Charlotte,Watts, Paul,Haswell, Stephen J.,Pombo-Villar, Esteban
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p. 10757 - 10773
(2007/10/03)
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- Stereoselective conjugate radical additions: Application of a fluorous oxazolidinone chiral auxiliary for efficient tin removal
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(Chemical Equation Presented) A series of asymmetric free-radical-mediated intermolecular conjugate additions using a fluorous oxazolidinone chiral auxiliary has been completed. The fluorous auxiliary facilitated product isolation using fluorous solid phase extractions (FSPE), effectively removing excess organic and organometallic reagents. Parallel reactions carried out with a similar but nonfluorous norephedrine-derived oxazolidinone demonstrated the superior stereoselectivity and purification obtainable with the fluorous chiral auxiliary.
- Hein, Jason E.,Zimmerman, Jake,Sibi, Mukund P.,Hultin, Philip G.
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p. 2755 - 2758
(2007/10/03)
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- Compounds which mimic the chemical and biological properties of discodermolide
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Compounds which mimic the chemical and/or biological activity of discodermolide are provided and intermediates useful in their preparation.
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- Carboxylation and Mitsunobu reaction of amines to give carbamates: Retention vs inversion of configuration is substituent-dependent
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(Equation Presented) A mild method for the synthesis of carbamates from amino alcohols involves sequential carboxylation with carbon dioxide, followed by a Mitsunobu reaction. Unexpectedly, the stereochemical course of the Mitsunobu reaction is dependent on whether the carbamic acid intermediate is N-substituted with hydrogen (retention) or carbon (inversion).
- Dinsmore, Christopher J.,Mercer, Swati P.
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p. 2885 - 2888
(2007/10/03)
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- Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: Isolation, structure determination, synthesis, and biological activity
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The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide (1), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1. The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S 3 cells with an IC50 of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1. Graphical abstract.
- Suenaga, Kiyotake,Mutou, Tsuyoshi,Shibata, Takunobu,Itoh, Takashi,Fujita, Tatsuya,Takada, Noboru,Hayamizu, Kozue,Takagi, Masaki,Irifune, Taiji,Kigoshi, Hideo,Yamada, Kiyoyuki
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p. 8509 - 8527
(2007/10/03)
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- A novel nucleophilic attack to N-enoyl oxazolidinethiones
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The oxazolidinethione synthon can act as a chiral auxiliary and nucleophile (S-) carrier molecule simultaneously. Surprisingly, the thiolate attacks N-enoyl oxazolidinethiones producing a new heterocycle, as established by X-ray analysis.
- Ortiz, Aurelio,Quintero, Leticia,Mendoza, Guadalupe,Bernès, Sylvain
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p. 5053 - 5055
(2007/10/03)
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- EPOTHILONE DERIVATIVES, METHOD FOR PRODUCING SAME AND THEIR PHARMACEUTICAL USE
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This invention relates to the new epothilone derivatives of general formula I, 1in which substituents Y, Z R2a, R2b, R3, R4a, R4b, D—E, R5, R6, R7, R8 and X have the meanings that are indicated in more detail in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanomas, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (psoriasis, arthritis). To avoid uncontrolled proliferation of cells and for better compatibility of medical implants, they can be applied or introduced into polymer materials. The compounds according to the invention can be used alone or to achieve additive or synergistic actions in combination with other principles and classes of substances that can be used in tumor therapy.
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- Catalytic activity of MCM-41-TBD in the selective preparation of carbamates and unsymmetrical alkyl carbonates from diethyl carbonate
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The synthesis of carbamates 3 and unsymmetrical alkyl carbonates 5 by reaction of diethyl carbonate with aliphatic amines or alcohols has been realized by using as heterogeneous catalyst a hybrid organic-inorganic material prepared by anchoring TBD to MCM-41 silica. Products are obtained in high yield and very good selectivity and the solid catalyst can be recovered simply by filtration and reused for different cycles without apparent lowering of activity. A supported N -carbethoxyguanidinium active intermediate is proposed, and some spectroscopic data are shown to support the mechanistic hypothesis.
- Carloni, Silvia,De Vos, Dirk E.,Jacobs, Pierre A.,Maggi, Raimondo,Sartori, Giovanni,Sartorio, Raffaella
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p. 199 - 204
(2007/10/03)
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- Chemoselective debezylation of the N-1-phenylethyl group in 2-oxazolidinones by the anisole-methanesulfonic acid system
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The chemoselective removal of N-1-phenylethyl group in 2-oxazolidinones by the anisole-methanesulfonic acid system was investigated. Optically active 4,5-cis- and 4,5-trans-diphenyl-2-oxazolidinones (1a-d) were easily synthesized from dl-stilbene oxides (trans- and cis-7a) using this debenzylation.
- Sugiyama, Shigeo,Morishita, Kenji,Chiba, Mariko,Ishii, Keitaro
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p. 637 - 648
(2007/10/03)
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- Synthesis of chiral oxazolidin-2-ones by 1,2-amino alcohols, carbon dioxide and electrogenerated acetonitrile anion
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An improved electrochemical synthesis of chiral oxazolidin-2-ones from chiral 1,2-amino alcohols is obtained by direct electrolysis of solutions of MeCN-TEAP containing the amino alcohol, with subsequent CO2 bubbling and addition of TsCl. This
- Feroci, Marta,Gennaro, Armando,Inesi, Achille,Orsini, Monica,Palombi, Laura
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p. 5863 - 5865
(2007/10/03)
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- Stereoselective synthesis of pamamycin-607
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A macrodiolide antibiotic pamamycin-607 was synthesized by joining two hydroxy acid components. Three cis-2, 5-disubstituted tetrahydrofuran rings in the molecule were stereoselectively prepared by radical cyclization reactions of β-alkoxyvinyl ketone intermediates and a β-alkoxymethacrylate substrate. The key step of the synthesis is characterized by the predominant threo product formation in the radical cyclization reaction of a β-alkoxymethacrylate intermediate.
- Jeong, Eun Jeong,Kang, Eun Joo,Sung, Lee Taek,Hong, Sung Kil,Lee, Eun
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p. 14655 - 14662
(2007/10/03)
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- Compounds which mimic the chemical and biological properties of discodermolide
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Compounds which mimic the chemical and/or biological activity of discodermolide are provided and intermediates useful in their preparation.
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- Total synthesis and absolute configuration of minalemine A, a guanidine peptide from the marine tunicate Didemnum rodriguesi
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The total synthesis of the 3S,2S and 3R,2S diastereomers (1a and 1b) of minalemine A and the identification of the natural compound as the 3R,2S isomer is described. The key step in the synthesis is the preparation of the two enantiomers of the β-amino diacid 3-(N-carboxymethyl)-aminodecanoic acid (Ncma), which were obtained by stereoselective alkylation with allyl bromide of two nonanoic acid imides bearing chiral oxazolidinones as chiral auxiliaries. Natural minalemine A shows identical 1H NMR and very similar 13C NMR spectra compared to the two synthetic diastereomers. Sufficient differences in their chromatographic behavior to allow conclusive identification were not found. However, the corresponding N-2-naphthoyl amides presented quite distinct circular dichroism spectra (CD), and these confirmed the 3R,2S configuration for the natural minalemines and the R configuration for the constituent β-amino diacid, Ncma.
- Exposito,Fernandez-Suarez,Iglesias,Munoz,Riguera
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p. 4206 - 4213
(2007/10/03)
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- The reaction of β-amino alcohols with 1,1′ -carbonyldiimidazole - Influence of the nitrogen substituent on the reaction course
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The reaction of β-amino alcohols with 1,1′carbonyldiimidazole in dichloromethane is affected by the size of the nitrogen substituent. 1,3-Oxazolidin-2-ones are exclusively obtained from N-H, N-methyl and N-arylmethyl derivatives. O-(1-Imidazolyl)carbonyl derivatives are formed as intermediates from N-[1-(2-pyridyl)alkyl]-(S)-valinol and are mainly or exclusively converted into aziridines in the presence of water, although the cyclization is impeded by large N-substituents such as triphenylmethyl.
- Cutugno, Sara,Martelli, Gianluca,Negro, Lucia,Savoia, Diego
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p. 517 - 522
(2007/10/03)
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- Palladium-catalyzed electrochemical carbonylation of 2-amino-1-alkanols to oxazolidin-2-ones under very mild conditions
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A new procedure for an efficient synthesis of oxazolidin-2-ones was developed. 2-Amino-1-alkanols undergo oxidative carbonylation under atmospheric pressure of carbon monoxide at room temperature using Pd(II) catalyst in combination with its anodic recycling at a graphite electrode.
- Chiarotto, Isabella,Feroci, Marta
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p. 3451 - 3453
(2007/10/03)
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- Synthetic techniques and intermediates for polyhydroxy, dienyl lactone derivatives
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Synthetic methods for lactone-containing compounds such as the discodermolides are provided, as are compounds which mimic the chemical and/or biological activity thereof, and methods and intermediates useful in their preparation.
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- Evolution of a gram-scale synthesis of (+)-discodermolide
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An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σr-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphonium salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.
- Smith III, Amos B.,Beauchamp, Thomas J.,LaMarche, Matthew J.,Kaufman, Michael D.,Qiu, Yuping,Arimoto, Hirokazu,Jones, David R.,Kobayashi, Kaoru
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p. 8654 - 8664
(2007/10/03)
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- Asymmetric synthesis and Lewis acid mediated type II carbonyl ene cyclisations of (R)-2-isopropyl-5-methylhex-5-enal
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The asymmetric synthesis of (R)-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Evans chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O-alkylation, a phenomenon not previously reported. Type II carbonyl ene cyclisation of the aldehyde with a range of Lewis acids led to either the (R,R)- or (R,S)-5-methylidenecyclohexanols without concurrent racemisation of the alpha stereogenic centre of the aldehyde. Conditions for effecting the easy racemisation of a model enantiomerically pure aldehyde, (S)-2-methylbutanal, were developed. In an effort to secure a dynamic kinetic resolution procedure, these conditions were applied to (R)-2-isopropyl-5-methylhex-5-enal. However, a competing and dominant Prins cyclisation occurred instead leading to a mixture of all possible cycloadducts, all of which were obtained in 98% ee. Any unreacted aldehyde was found to be enantiomerically pure. Copyright (C) 2000 Elsevier Science Ltd.
- Braddock, D. Christopher,Brown, John M.
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p. 3591 - 3607
(2007/10/03)
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- Application of oxazolidinone α-fluoro amide chiral building blocks in the asymmetric synthesis of fluorinated carbohydrates: 2-Deoxy-2-fluoropentoses
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Deconjugative electrophilic fluorination of the lithium dienolate of Z-α,β-unsaturated imide (+)-9 with N-fluorobenzene-sulfonimide (NFSi) afforded the E-β,γ-unsaturated α-fluoro imide (+)-10 as a single diastereoisomer. Dihydroxylation resulted in the formation of 2-fluoro-2-deoxy-γ-xylonic and -lyxonic lactones, 12a and 12b, respectively. Reduction and deprotection of the lactones afforded 2-deoxy-2-fluoro-xylo-D-pyranose (15) and 2-deoxy-2-fluoro-lyxo-L-pyranose (17). (C) 2000 Elsevier Science Ltd.
- Davis, Franklin A.,Qi, Hongyan,Sundarababu, Gajendran
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p. 5303 - 5310
(2007/10/03)
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