- A new class of C2-symmetric diphosphine ligands derived from valine: Remarkably diverse behavior in catalytic asymmetric transformations
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A new C2-symmetric diphosphine ligand 8a was readily prepared in one step by treatment of the synthetic precursor of VALAP, 7, with phthaloyl chloride. Remarkably high levels of asymmetric induction, over 99% ee, were achieved using 8a in palladium-catalyzed asymmetric allylic transformations of sterically less demanding cyclohexenyl substrates 9. The ligand system was easily extended to the development of analogous chiral auxiliaries 8b,c by the identical procedure but using isophthaloyl chloride and succinyl chloride. However, the ligands 8b,c exhibited much lower catalytic activity. In contrast to the asymmetric allylic substitutions, 8c demonstrated significant improvement of enantioselectivity, up to 64% ee, in rhodium- catalyzed asymmetric hydrosilylations of acetophenone 11a compared to 35% ee using 8a. In this way, the versatility of the present ligand system played an important role in variations of substrates and reaction types. (C) 1999 Elsevier Science Ltd.
- Saitoh, Akihito,Uda, Takashi,Morimoto, Toshiaki
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- Design, synthesis, and structure-activity relationship studies of L-amino alcohol derivatives as broad-spectrum antifungal agents
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To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of L-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1–2 μg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent.
- Zhao, Liyu,Tian, Linfeng,Sun, Nannan,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
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p. 374 - 385
(2019/06/05)
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- A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
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An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
- Bera, Saurav,Panda, Gautam
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p. 3976 - 3985
(2014/06/09)
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- Synthesis of iron P-N-P' and P-NH-P asymmetric hydrogenation catalysts
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Complexes of the type mer,trans-[Fe(P-N-P)(CO)2Br]BF4 are known to be precatalysts for the asymmetric direct hydrogenation of ketones and imines. Employing related ligand scaffolds, we successfully generated and tested the series of three new precatalysts [Fe(PCy2CH2CH-NCH(R)CH2PPh2)(CO)2Br]BF4 with chirality derived from (S)-amino alcohols with phenyl, benzyl, and isopropyl substituents (R), yielding fairly active and selective systems. For the reduction of acetophenone to (S)-1-phenylethanol turnover frequencies up to 920 h-1 and up to 74% enantiomeric excess at 50 °C and 5-25 atm of H2 were obtained. We found, however, that placing these large groups R next to nitrogen was found to be deleterious to catalytic activity. Extending the scope of the ligand structure, we then developed a series of six P-N-P and five P-NH-P systems starting with o-diphenylphosphinobenzaldehyde and the phosphine-amines PPh2CHR1CHR2NH2 (R1 = H, Ph, CH2Ph, iPr with R2 = H or R1 = Me, Ph with R2 = Ph) as well as their corresponding [Fe(P-N-P)(NCMe)3][BF4]2 and [Fe(P-NH-P)(NCMe)3][BF4]2 complexes, which were not catalytically active. Finally, we made the new achiral iron complex mer,cis-Fe(PPh2(o-C6H4)CHNCH2CH2PPh2)(CO)Br2, which was active for the direct hydrogenation of acetophenone, achieving turnover frequencies of 800 h-1 at 50°C and 25 atm of H2.
- Sonnenberg, Jessica F.,Lough, Alan J.,Morris, Robert H.
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supporting information
p. 6452 - 6465
(2015/02/19)
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- Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
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An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
- Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
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scheme or table
p. 865 - 872
(2010/09/16)
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- Synthesis of new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines from α-amino acid derivatives under mild conditions
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A practical and efficient regioselective synthesis of several new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines is described from α-amino acid derivatives following intramolecular 'click' reaction as the key step. The method obviates product pu
- Mohapatra, Debendra K.,Maity, Pradip K.,Gonnade, Rajesh G.,Chorghade, Mukund S.,Gurjar, Mukund K.
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p. 1893 - 1896
(2008/03/13)
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- Radical addition approach to asymmetric amine synthesis: Design, implementation, and comparison of chiral N-acylhydrazones
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Intermolecular radical addition to C=N bonds with acyclic stereocontrol offers excellent potential as a mild, nonbasic carbon-carbon bond construction approach to chiral amines. Here, complete details of the first radical additions to chiral N-acylhydrazones as an approach to asymmetric amine synthesis are disclosed. Novel N-acylhydrazones were designed as chiral C=N radical acceptors with Lewis acid activation, restriction of conformational mobility, and commercial availability of precursors. Amination of 4-alkyl-2-oxazolidinones with O-(mesitylenesulfonyl)hydroxylamine or O-(p-nitrobenzoyl)hydroxylamine afforded N-aminooxazolidinones which were condensed with aldehydes to afford N-acylhydrazones 3-8. Three synthetic methods were developed, implementing these N-acylhydrazones in Lewis acid-promoted intermolecular radical additions to C=N bonds. First, additions of various secondary and tertiary alkyl iodides to propionaldehyde and benzaldehyde hydrazones (3 and 7) under tin hydride radical chain conditions in the presence of ZnCl2 gave N-acylhydrazine adducts with diastereomeric ratios ranging from 93:7 to 99:1. Radical additions to a series of N-acylhydrazones with different substituents on the oxazolidinone revealed that benzyl and diphenylmethyl were more effective stereocontrol elements than those with the aromatic ring directly attached to the oxazolidinone. Second, a tin-free method, exploiting dual functions of triethylborane for both initiation and chain propagation, enabled improved yields in addition of secondary alkyl iodides. Third, under photolytic conditions with hexamethylditin, primary radical addition could be achieved with ethyl iodide in the presence of diethyl ether as cosolvent; the 1-ethoxyethyl adduct was observed as a minor product. Chloromethyl addition was achieved under both the tin-free and photolytic conditions; in this case, the adduct bears alkyl chloride functionality with potential for further elaboration.
- Friestad, Gregory K.,Draghici, Cristian,Soukri, Mustapha,Qin, Jun
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p. 6330 - 6338
(2007/10/03)
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- Synthesis and reactivities of enantiomerically pure β hydroxyalkyl and β-aminoalkyl ferrocenyl sulfides
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Enantiomerically pure β-hydroxyalkyl and β-aminoalkyl ferrocenyl sulfides have been synthesized in good yields from mercaptoferrocene and amino alcohol derivatives. Primary β-aminoalkyl sulfides allowed the synthesis of tetrahydro-1,4-thiazepines containing the ferrocene moiety with good diastereoselectivity and β-iminoalkyl sulfides. Some of these derivatives have successfully been employed as ligands for palladium-catalyzed allylic substitution, with asymmetric induction of up to 99% ee. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Bernardi, Luca,Bonini, Bianca F.,Comes-Franchini, Mauro,Fochi, Mariafrancesca,Mazzanti, Germana,Ricci, Alfredo,Varchi, Greta
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p. 2776 - 2784
(2007/10/03)
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- Stereoselective synthesis of 2-alkenylaziridines and 2-alkenylazetidines by palladium-catalyzed intramolecular amination of α- and β-amino allenes
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Whereas palladium-catalyzed reaction of N-arylsulfonyl-α-amino allenes with an aryl iodide (4 equiv) in the presence of potassium carbonate (4 equiv) in DMF at around 70 °C affords the corresponding 3-pyrroline derivatives, the reaction in refluxing 1,4-dioxane under otherwise identical conditions yields exclusively or most predominantly the corresponding 2-alkenylaziridines bearing an aryl group on the double bond. Similarly, N-arylsulfonyl-β-amino allenes can be also cyclized into the corresponding alkenylazetidines bearing a 2,4-cis-configuration under palladium-catalyzed cyclization conditions in DMF.
- Ohno,Anzai,Toda,Ohishi,Fujii,Tanaka,Takemoto,Ibuka
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p. 4904 - 4914
(2007/10/03)
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- Synthesis of heterofunctionalized multidentate diphosphines
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The synthesis of new chiral multidentate amino- and amidophosphine ligands bearing up to six potential coordination sites were synthesized starting from L-valine. Based on these compounds chiral Ru(II) complexes were prepared, characterized and tested in the asymmetric transfer hydrogenation of aryl-alkyl ketones. In all cases investigated the catalyst bearing additional hydroxy groups gave lower conversions than the complex without hydroxy groups. Highest enantioselectivity was achieved with isobutyrophenone as substrate (69%ee). (C) 2000 Elsevier Science Ltd.
- Quirmbach, Michael,Holz, Jens,Tararov, Vitali I.,B?rner, Armin
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p. 775 - 780
(2007/10/03)
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- Chemoenzymatic synthesis of 4-amino-2-hydroxy acids: A comparison of mutant and wild-type oxidoreductases
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We describe a new chemoenzymatic synthesis of enantiopure 4-amino-2-hydroxy acids using two biotransformations in a single-pot process in aqueous medium. These compounds are valuable as γ-turn mimics for investigations into the secondary structure of peptides. The enzyme substrates are a series of carbobenzyloxy (CBZ)-protected 4-amino-2-keto esters, prepared efficiently from the L-amino acids, alanine, leucine, phenylalanine, and valine. First, the α-amino acids were converted to the corresponding β-amino acids in a simple five-step procedure. A further one-carbon homologation via ozonolysis of the corresponding β-keto cyanophosphoranes gave the required α-keto esters in good yield. The enzyme catalyzed hydrolyses of all the α-keto esters to the corresponding α-keto acids proceeded smoothly with the lipase from Candida rugosa. Using the same reaction pot, it was found that wild-type lactate dehydrogenases from either Bacillus stearothermophilus CBS-LDH) or Staphylococcus epidermidis (SE-LDH) could be used to specifically reduce the ketone of the alanine-derived α-keto acid 2, giving the (S)- and CR)-2-hydroxy acids, respectively, in good yields. However, the more bulky α-keto acids 3, 4, and 5 (derived from valine, leucine, and phenylalanine) were not substrates for these enzymes. In contrast, the genetically engineered H205Q mutant of D-hydroxyisocaproate dehydrogenase proved to be an ideal catalyst for the reduction of all the α-keto acids 2-5, giving excellent yields of the CBZ-protected (2R,4S)-4-amino2-hydroxy acids as single diastereomers. This genetically engineered oxidoreductase has great potential value in synthesis due to its broad substrate specificity and high catalytic activity. For example, reduction of 1 mmol of N-protected (S)-4-amino-2-oxopentanoic acid 2 took just 4 h with the H205Q mutant giving, after esterification, the CR)-2-alcohol 25 in 85% yield, whereas with SE-LDH the reaction required 4 days to give a 67% yield of 25.
- Sutherland, Andrew,Willis, Christine L.
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p. 7764 - 7769
(2007/10/03)
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- A phosphorus-containing chiral amidine ligand for asymmetric reactions: Enantioselective Pd-catalyzed allylic alkylation
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Phosphorus-containing amidine 7 was prepared through several steps from L-valine 1. The new ligand for asymmetric reactions was evaluated in the palladium-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate and pivalate 8a,b with the nucleophile derived from dimethyl malonate as a preliminary study. Excellent levels of asymmetric induction up to 95% e.e. were achieved along with an efficient conversion.
- Saitoh, Akihito,Morimoto, Toshiaki,Achiwa, Kazuo
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p. 3567 - 3570
(2007/10/03)
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- Synthesis of (β-N-sulfonylaminoalkyl)phosphines and their use in palladium-mediated asymmetric synthesis
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A series of (β-N-sulfonylaminoalkyl)phosphine ligands has been developed and employed for asymmetric palladium-catalyzed hydrosilylation and Heck-type hydroarylation, affording up to 72% ee and 90% yield.
- Sakuraba,Okada,Morimoto,Achiwa
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p. 927 - 934
(2007/10/02)
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- The Palladium-catalyzed Asymmetric Allylations of Chiral Hydrazones Bearing Phosphine Groups. Stereoelectronic Effects of Allylating Reagents on Asymmetric Induction
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The palladium-catalyzed allylations of chiral hydrazones bearing phosphine groups were executed successfully under neutral reaction conditions with various allylating reagents, affording optically active α-allyl carbonyl compounds.The systematic and stere
- Hiroi, Kunio,Haraguchi, Mitsuhiro,Masuda, Yoko,Abe, Jun
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p. 2409 - 2412
(2007/10/02)
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- The role of hydroxymethyl function on the biological activity of the antitumor antibiotic sparsomycin
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The synthesis is described of the sparsomycin analogues 11-14 from the L-amino acids valine, isoleucine, phenylalanine and proline, respectively. The sparsomycin derivative 21 was not prepared in a similar way from glycine, but from cystamine following a different reaction route. These analogues, as well as the O-methylated and O-acetylated derivatives 15 and 16, respectively, were tested in vitro for their protein synthesis inhibitory activity and for their inhibition of colony formation of murine leukemia L1210 cells. The results of these assays indicate that the hydroxymethyl function of 1 is not essential for its biological activity, and that increase of lipophilicity in this 'northern' region of 1 does not noticeably affect the activity of the drug.
- Van den Broek,Fennis,Arevalo,Lazaro,Ballesta,Lelieveld,Ottenheijm
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p. 503 - 510
(2007/10/02)
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- Sparsomicin (Sc-Rs) compounds having antitumor activity, a process for their preparation and pharmaceutical compositions containing sparsomycin (Sc-Rs) compounds
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The invention relates to novel sparsomycin (Sc-Rs) compounds having valuable antitumor activity, and to a process for their preparation and pharmaceutical compositions containing such novel compounds. The novel compounds satisfy the general formula
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- Sparsomycin (SC-RS) compounds having antitumor activity, a process for their preparation and pharmaceutical compositions containing sparsomycin (SC-RS) compounds
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The invention relates to novel sparsomycin (Sc -Rs) compounds having valuable antitumor activity, and to a process for their preparation and pharmaceutical compositions containing such novel compounds. The novel compounds satisfy the general formula STR1
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