- One-Pot Reductive Allylation of Amides by Using a Combination of Titanium Hydride and an Allylzinc Reagent: Application to a Total Synthesis of (-)-Castoramine
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A one-pot direct reductive allylation protocol has been developed for the synthesis of secondary amines by using titanium hydride and an allylzinc reagent. This protocol is applicable to a broad range of substrates, including acyclic amides, benzamides, α,β-unsaturated amides, and lactams. The stereochemical outcome obtained from the reaction with crotylzinc reagent suggested that the allylation reaction proceeds through a six-membered cyclic transition state. A total synthesis of (-)-castoramine was accomplished by following this protocol for the highly stereoselective construction of contiguous stereocenters.
- Itabashi, Suguru,Shimomura, Masashi,Sato, Manabu,Azuma, Hiroki,Okano, Kentaro,Sakata, Juri,Tokuyama, Hidetoshi
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supporting information
p. 1786 - 1790
(2018/07/03)
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- Ring-chain tautomerism in 2,2-bis(2-thienyl)-tetrahydrofurans: Preparation of [butene-2H5]-tiagabine
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A concise preparation of [butene-2H5]-tiagabine hydrochloride starting from [2H6]-γ-butyrolactone is described. It was necessary to ring-open the labeled γ-butyrolactone precursor before the addition of 2-thienyllithium to avoid cyclisation of the intermediate to a 2,2-bis(2-thienyl)tetrahydrofuran. Copyright
- Herberta, John M.,Mathersa, Trevor W.
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experimental part
p. 598 - 600
(2011/05/12)
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- 4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: Design, synthesis and structure-activity relationships
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Single enantiomer [(aryloxy)(pyridinyl)methyl]piperidine and pyrrolidine derivatives 5-9 are inhibitors of monoamine reuptake. Structure-activity relationships established that monoamine reuptake inhibition are functions of amine, pyridine isomer, aryloxy ring substitution and stereochemistry. Consequently, selective NRIs, selective SRIs, dual SNRIs and triple SNDRIs were all identified. Dual SNRIs 5l-a and 9c were evaluated in additional pharmacology and pharmacokinetic studies as representative examples from this series.
- Fish, Paul V.,Andrews, Mark D.,Jonathan Fray,Stobie, Alan,Wakenhut, Florian,Whitlock, Gavin A.
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scheme or table
p. 2829 - 2834
(2010/03/03)
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- FARNESYL PROTEIN TRANSFERASE INHIBITORS
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Disclosed are compounds of formula (1.0), wherein R represents a cyclic moiety to which is bound an imodazolylalkyl group; R represents a carbamate, urea, amide or sulfonamide group; and the remaining substituents are as defined herein. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
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Page/Page column 33
(2010/02/11)
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- Preparation of β2-amino acid derivatives (β2hThr, β2hTrp, β2hMet, β2hPro, β2hLys, pyrrolidine-3-carboxylic acid) by using DIOZ as chiral auxiliary
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The title compounds were prepared from valine-derived N-acylated oxazolidin-2-ones, 1-3, 7, 9, by highly diastereoselective (≥ 90%) Mannich reaction (→ 4-6; Scheme 1) or aldol addition (→ 8 and 10; Scheme 2) of the corresponding Ti- or B-enolates as the key step. The superiority of the '5,5-diphenyl-4-isopropyl-1,3-oxazolidin-2-one' (DIOZ) was demonstrated, once more, in these reactions and in subsequent transformations leading to various t-Bu-, Boc-, Fmoc-, and Cbz-protected β2-homoamino acid derivatives 11-23 (Schemes 3-6). The use of ω-bromo-acyl-oxazolidinones 1-3 as starting materials turned out to open access to a variety of enantiomerically pure trifunctional and cyclic carboxylic-acid derivatives.
- Gessier, Francois,Schaeffer, Laurent,Kimmerlin, Thierry,Floegel, Oliver,Seebach, Dieter
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p. 2235 - 2249
(2007/10/03)
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- An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764
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An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764 was achieved. The key intermediate, an optically active ethynyl β-amino ester, was synthesized efficiently by utilizing a lipase catalyzed kinetic resolution step.
- Yamanaka, Toshio,Ohkubo, Mitsuru,Takahashi, Fumie,Kato, Masayuki
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p. 2843 - 2845
(2007/10/03)
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- Novel farnesyl protein transferase inhibitors as antitumor agents
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Disclosed are novel tricyclic compounds represented by the formula (1.0): and a pharmaceutically acceptable salt or solvate thereof. The compounds are useful for inhibiting farnesyl protein transferase. Also disclosed are pharmaceutical compositions comprising compounds of formula 1.0. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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- N-HETEROCYCLYL-SUBSTITUTED AMINO-THIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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Aminothiazole compounds with N-containing cycloalkyl at the 2-amino position which are represented by the Formula (I), or a pharmaceutically acceptable prodrug of said compound, or pharmaceutically acceptable salt of said compound, modulate and/or inhibit the cell proliferation and activity of protein kinases.
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- Novel farnesyl protein transferase inhibitors as antitumor agents
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Disclosed are novel tricyclic compounds represented by the formula (1.0): or a pharmaceutically acceptable salt or solvate thereof. The compounds are useful for inhibiting farnesyl protein transferase. Also disclosed are pharmaceutical compositions comprising compounds of formula 1.0. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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- Method for optical resolution of piperidine carboxylic acid derivative
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A method for producing an optically active piperidine carboxylic acid derivative, which comprises subjecting a piperidine carboxylic acid derivative of the formula (1): wherein Z is a protecting group for the carboxyl group, to optical resolution by means of an optical resolution agent of the formula (2): wherein symbol * indicates that the designated carbon atom is asymmetric.
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Page column 3
(2008/06/13)
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- Beta lactam compounds and their use as inhibitors of tryptase
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Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.
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Page column 248
(2010/11/29)
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- NOVEL AMIDE DERIVATIVES
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This invention relates to compounds which are represented by the general formula [I] ???[in which A stands for a group of the following formula [ao] or [b0] ???Ar1, Ar2 and Ar3 stand for optionally substituted phenyl; k stands for 0 or 1; m, n and s stand for 0, 1 or 2; R1 stands for hydrogen or optionally substituted lower alkyl; R2, R3, R4 and R5 either stand for hydrogen or optionally substituted lower alkyl, or R2 and R3, or R4 and R5 together stand for trimethylene and the like; R60 stands for hydrogen, alkyl, or the like; R61and R71 either stand for alkyl and the like, or together stand for trimethylene and the like; X stands for carbonyl or methylene; Y stands for nitrogen or methine; and Q- stands for anion], and the like. The compounds of the invention exhibit selective antagonism to muscarinic M3 receptors, and therefore are useful as safe and effective agents showing little side effect, for treating diseases of the respiratory, urinary and digestive systems.
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- Oligomers of β2- and of β3-homoproline: What are the secondary structures of β-peptides lacking H-bonds?
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To study the role of H-bonds in stabilizing β-peptidic secondary structures, we have synthesized β-oligopeptides (up to the octadecamer 12) consisting of β2- and β3-homoproline, i.e., β-peptides lacking amide protons. The enantiomer purity of the building block β2-homoproline (nipecotic acid, 4) was determined by HPLC analysis of the N-(2,4- dinitrophenyl) derivative 5 on a Chiralcel-OD column (cf. Fig. 2). The CD spectra of the all-(S)-β2- and all-(S)-β3-HPro-containing, β-peptides display novel and intensive CD patterns which may be indicative of a secondary structure (cf. Fig. 3). It is noteworthy that a distinct CD pattern was observed with the β3-HPro derivatives containing as few as three residues (7a). The crystal structure of a N-deprotected β3-HPro-tripeptide 7c is presented (cf. Figs. 4 and 5), and a model for the structure of β- peptides consisting of β3-HPro is discussed (cf. Figs. 6 and 7).
- Abele, Stefan,Voegtli, Kurt,Seebach, Dieter
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p. 1539 - 1558
(2007/10/03)
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- Enantioselective addition of diethylzinc to aldehydes catalyzed by ethyl nipecotate- derived new chiral ligand
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(R)-(-)-Diphenyl-(N-methylpiperidin-3-yl)methanol (3) derived from (±)- ethyl nipecotate catalyzed the enantioselective addition of diethylzinc to various aldehydes in good to moderate optical yield (40% - 81%).
- Lee, So Ha,Im, Dai Sig,Cheong, Chan Seong,Chung, Bong Young
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p. 1913 - 1919
(2007/10/03)
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