- Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters
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A new class of chiral C2-symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd-catalyzed asymmetric N-allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional SN2-coupling of a tartrate-derived ditosylate with 6-alkyl-2-bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd-catalyzed N-allylation of tert-butyl glycinate with racemic (E)-2,8-dimethylnona-5-en-4-yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert-butyl glycinate with methyl (E)-nona-5-en-4-yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline-derived dipeptide analogs ProM-17 and ProM-21.
- Albat, Dominik,Neud?rfl, J?rg-Martin,Reiher, Martin,Schmalz, Hans-Günther
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supporting information
p. 4237 - 4242
(2021/08/24)
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- Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization
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A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of ω-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including α,β-unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity.
- Ganss, Stephanie,Breit, Bernhard
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p. 9738 - 9742
(2016/08/10)
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- Optimization of an electrolyte system for the simultaneous separation of nelfinavir mesylate and two impurities by micellar electrokinetic chromatography
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A methodology for the simultaneous determination of nelfinavir mesylate and the impurities 3-hydroxy-2-methylbenzoic acid and (2R,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl) octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-(phenylthio)butan-2-aminium benzoate by micellar electrokinetic chromatography, with an analysis time of 25 min, was proposed. An electrolyte composed of sodium tetraborate buffer (pH 9.24; 25 mmol L-1), sodium dodecyl sulphate (9 mmol L-1) and methanol (10percent, v/v) was optimized using a mixed-level factorial design, with direct detection at 200 nm. After evaluating some figures of merit, such as selectivity, linearity, precision, limit of detection, limit of quantification, accuracy and robustness (using Youden's test), the method was successfully applied to the analysis of nelfinavir mesylate and its impurities in a pharmaceutical formulation. The optimized methodology is demonstrated to be useful in the determination of these analytes in a synthesis monitoring process, in raw materials and in pharmaceutical formulations, while offering low solvent consumption, requiring a small sample and using non-specific columns as advantages.
- Bastos, Carina A.,Gomes, Cláudia R. B.,De Souza, Marcus V. N.,De Oliveira, Marcone A. L.
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p. 887 - 898
(2015/05/20)
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- NEUROLOGICALLY-ACTIVE COMPOUNDS
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The invention provides a compound of the formula (I): wherein R is methyl, ethyl, propyl, isopropyl, butyl, pentyl, neo-pentyl or cyclohexyl, or a salt or solvate thereof. These compounds are selective GABAC receptor antagonists. The invention also provides pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The invention also provides methods of enhancing the cognitive activity of an animal and methods of stimulating memory capacity in an animal, comprising the step of administering to the animal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof.
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Page/Page column 11; 13
(2008/06/13)
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- A synthesis of the HIV-protease inhibitor nelfinavir from D-tartaric acid
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This letter describes a new synthesis of the HIV-protease inhibitor nelfinavir. The synthesis features a selective opening of a D-tartaric acid-derived cyclic sulfate with nitrogen nucleophiles.
- Albizati, Kim F.,Babu, Srinivasan,Birchler, Angela,Busse, Juliette K.,Fugett, Michelle,Grubbs, Alan,Haddach, Aubrey,Pagan, Miguel,Potts, Barbara,Remarchuk, Travis,Rieger, Dale,Rodriguez, Rick,Shanley, Jim,Szendroi, Robert,Tibbetts, Tony,Whitten, Kathleen,Borer, Bennett C.
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p. 6481 - 6485
(2007/10/03)
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- Radical cyclization of β-alkoxyacrylates: A formal synthesis of (-)-kumausallene
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Radical cyclization reaction of a bis(β-alkoxyacrylate) intermediate prepared from (-)-diethyl D-tartrate proceeded stereoselectively to give a 2,6-dioxabicyclo[3.3.0]octane product, which was converted into a known intermediate in the synthesis of kumausallene.
- Lee, Eun,Yoo, Sang-Ku,Choo, Hyunah,Song, Ho Young
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p. 317 - 318
(2007/10/03)
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- Synthesis of (3R)-3-Hydroxy-2-hexanone, (2R,3R)-2,3-Hexanediol and (2S,3R)-2,3-Hexanediol, the Male Sex Pheromone of Hylotrupes bajulus and Pyrrhidium sanguineum (Cerambycidae)
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The following compounds were identified as male pheromone components of the longhorn beetles Hylotrupes bajulus and Pyrrhidium sanguineum: (3R)-3-hydroxy-2-hexanone , (2S,3R)-2,3-hexanediol and (2R,3R)-2,3-hexanediol .The syntheses of enantiomerically pure samples, enantiomeric separation by chiral gas chromatography and unambiguous structure assignment of the target compounds are described. - Key Words: Cerambycidae / Longhorn beetle / Pheromones / Ketones, α-hydroxy- / Hylotrupes bajulus / Pyrrhidium sanguineum
- Schroeder, Frank,Fettkoether, Regina,Noldt, Uwe,Dettner, Konrad,Koenig, Wilfried A.,Francke, Wittko
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p. 1211 - 1218
(2007/10/02)
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- Efficient Asymmetric Syntheses of Naturally Occurring Lignan Lactones Using Catalytic Asymmetric Hydrogenation as a Key Reaction
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Optically pure (R)-arylmethylsuccinic acid mono-methyl esters were obtained efficiently by using the catalytic asymmetric hydrogenation of arylidenesuccinic acid monoesters with a rhodium(I) complex of a chiral bisphosphine, (4S,5S)-MOD-DIOP.Asymmetric total syntheses of some naturally occurring lignans, (+)-collinusin, (-)-deoxypodophyllotoxin, and (+)-neoisostegane, were achieved via several steps from (R)-γ-butyrolactones as key intermediates obtained by reduction of (R)-arylmethylsuccinic acid mono methyl-esters.
- Morimoto, Toshiaki,Chiba, Mitsuo,Achiwa, Kazuo
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p. 1793 - 1806
(2007/10/02)
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- Synthesis and the Absolute Configuration of Panaxacol
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Panaxacol, a polyacetylene isolated from the callus of Panax ginseng, was synthesized from D-(-)-diethyl tartrate.The absolute configuration of panaxacol was determined to be 9R,10R.
- Fujimoto, Yasuo,Satoh, Mitsuru,Takeuchi, Naoki,Kirisawa, Makoto
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p. 1619 - 1622
(2007/10/02)
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- STEREOSPECIFIC SYNTHESIS OF ISOMERIC 4-SUBSTITUTED 9-(2,3-DIHYDROXYBUTYL)ADENINES
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Reduction of ethyl 2,3-O-isopropylidene-D-tartrate with sodium borohydride afforded (4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (Va) which was benzoylated to give monobenzoyl derivative Vd and further transformed into p-toluenesulfonyl derivative Ve.Reaction of the compound Ve with sodium salt of adenine followed by methanolysis gave 2,3-O-isopropylidene derivative Vf which on acid hydrolysis afforded 9-(2S,3S)-(2,3,4-trihydroxybutyl)adenine (Ia).The enantiomer IIa was obtained from 3,4-O-isopropylidene-D-mannitol via (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (VIa) using the same procedure.Reaction of compounds Vf and VIf with p-toluenesulfonyl chloride afforded 4-O-p-toluenesulfonyl derivatives Vg and VIg.These compounds were also obtained from Va and VIa via di-p-toluenesulfonyl derivatives Vc and VIc by reaction with sodium salt of adenine.Treatment of compounds Vg and VIg with sodium iodide gave 4-iodo derivatives Vh and VIh which on reaction with tri-n-butyltin hydride, followed by acid hydrolysis, afforded enantiomeric threo-2,3-dihydroxybutyl derivatives Ib and IIb.Compounds Vg and VIg on treatment with sodium azide, subsequent catalytic hydrogenation of the intermediates Vj and VIj and acid hydrolysis afforded enantiomeric threo-9-(4-amino-2,3-dihydroxybutyl)adenines (Ic, IIc).Reaction of methyl threo-3-phenylglycerate (VIIb) with acetone, followed by reduction with lithium aluminum hydride, gave 2,2-dimethyl-4-phenyl-1,3-dioxolane-5-methanol (VIIIb) which was converted by reaction with p-toluenesulfonyl chloride, condensation with sodium salt of adenine and acid hydrolysis into 9-(RS)-threo-(3-phenyl-2,3-dihydroxypropyl)adenine (I, IId).Methyl ester of D-eritadenine (IXb) was transformed into 2,3-O-isopropylidene derivative XIa which on reduction with sodium borohydride afforded the alcohol XIb.Its acid hydrolysis gave 9-(2R,3S)-erythro-(2,3,4-trihydroxybutyl)adenine (IIIa); tosylation of compound XIb, successive treatment with sodium iodide and tri-n-butyltin hydride and acid hydrolysis afforded 9-(2R,3S)-erythro-(2,3-dihydroxybutyl)adenine (IIIb).The enantiomers IVa and IVb were obtained analogously from L-eritadenine.The racemic derivative Ib + IIb was prepared from (RS)-threo-2,3-dihydroxybutyric acid via p-toluenesulfonyl derivative of racemic 2,2,4-trimethyl-1,3-dioxolane-5-methanol (IIIc) by reaction of sodium salt of adenine followed by acid hydrolysis.
- HOLY, Antonin
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p. 173 - 189
(2007/10/02)
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