- Capture-ROMP-release: Application to the synthesis of amines and alkyl hydrazines
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Application of a capture-ROMP-release strategy for the chromatography-free purification of Mitsunobu reaction products is described. Norbornenyl-tagged reagents are utilized for standard solution phase Mitsunobu chemistry. Post-reaction phase-switching is accomplished via in situ ring-opening metathesis polymerization (ROMP) followed by precipitation of the polymer with methanol. Release of the product from the polymer affords amines and alkyl hydrazine derivatives with good yields and purities.
- Mukherjee, Shubhasish,Poon, Kevin W. C.,Flynn, Daniel L.,Hanson, Paul R.
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Read Online
- Chiral tetraaryl-and tetraalkynylborates as chiral solvating agents for tetraalkylammonium salts
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The application of tetracarbon-substituted chiral borate sodium salts (NaBR*4) as NMR chiral solvating agents for various tetraalkylammonium salts (R4NX) has been successfully demonstrated. Ion exchange between R4NX and NaBR*4 proceeded in excellent yields and provided the corresponding dia-stereomeric salts (R4NBR*4). The ee values of the R4NX salts were determined by1H NMR analysis of R4NBR*4. Two types of chiral borates, tetraaryl-and tetraalkynylborates with optically active 1,1′-binaphthyl components were used. At the beginning of this research, we investigated the efficacy of a known chiral tetraar-ylborate developed by Pommerening et al. for R4NX. To expand the possibility of further structural design of the chiral borate, we designed chiral tetraalkynylborates as a new structure. Their synthesis and application are also described.
- Tayama, Eiji,Sugawara, Takeshi
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p. 803 - 811
(2019/01/18)
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- Recoverable Dendritic Phase-Transfer Catalysts that Contain (+)-Cinchonine-Derived Ammonium Salts
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Four new phosphorus dendrimeric phase-transfer catalysts are prepared that contain 12 (+)-cinchoninium salts on the surface obtained by the quaternisation of the quinuclidinic N atom. The asymmetric alkylation of a glycinate Schiff base with benzyl bromide is used as a benchmark reaction, and the dendrimeric catalyst that contains an allyl group on the O-9 hydroxy group of the cinchonine units is the most active. The recovery and reuse of the catalyst are possible for five consecutive runs without loss of activity and with only a slight decrease in enantioselectivity. If other electrophiles are used, substituted benzyl bromides give better results than other activated alkyl bromides to afford the corresponding R amino acid derivatives. A comparison of these results with those reported previously for similar cinchoninium salts shows that dendrimers could be a better support than other polymers for this type of organocatalysis.
- Rull, Jordi,Jara, José Juan,Sebastián, Rosa M.,Vallribera, Adelina,Nájera, Carmen,Majoral, Jean-Pierre,Caminade, Anne-Marie
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p. 2049 - 2056
(2016/07/07)
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- A practical aryl unit for azlactone dynamic kinetic resolution: Orthogonally protected products and a ligation-inspired coupling process
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The first strategy for bringing about enantioselective azlactone dynamic kinetic resolution to generate orthogonally protected amino acids has been developed. In the presence of a C2-symmetric squaramide-based catalyst, benzyl alcohol reacts with novel yet readily prepared tetrachloroisopropoxycarbonyl-substituted azlactones to generate trapped phthalimide products of significant synthetic interest with excellent enantiocontrol. These materials are masked amino acids which are demonstrably orthogonally protected: cleavage of the phthalimide can be achieved in the presence of the ester and vice versa. This process could be utilized to bring about a highly stereoselective ligation-type coupling of protected serines (at stoichiometric loadings) with racemic azlactones derived from both natural and abiotic amino acids. After deprotection, a subsequent base-mediated Oa??N acyl transfer occurs to form a dipeptide.
- Tallon, Sean,Manoni, Francesco,Connon, Stephen J.
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supporting information
p. 813 - 817
(2015/02/19)
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- Enantioselective synthesis of 1,2,4-triazolines by chiral iron(ii)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates
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Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by FeII-N,N′-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities.
- Wang, Min,Liu, Xiaohua,He, Peng,Lin, Lili,Feng, Xiaoming
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supporting information
p. 2572 - 2574
(2013/04/10)
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- An efficient asymmetric biomimetic transamination of α-keto esters to chiral α-amino esters
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An efficient asymmetric biomimetic transamination of α-keto esters with quinine derivatives as chiral bases was described. A wide variety of α-amino esters containing various functional groups can be synthesized in high yield and enantioselectivity.
- Xiao, Xiao,Liu, Mao,Rong, Chao,Xue, Fazhen,Li, Songlei,Xie, Ying,Shi, Yian
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supporting information
p. 5270 - 5273
(2013/01/15)
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- MODULATORS OF TLR3/DSRNA COMPLEX AND USES THEREOF
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The present invention provides compounds and compositions that can modulate formation of Toll-like receptor 3 (TLR3) and double-stranded RNA (dsRNA) complex, and methods for using the same. In particular, some aspects of the invention provide compounds of the formula (I) compositions comprising and methods for using the same, where n, Ar1, Ar2, X1, X2, X3, Z1, and Z2 are those defined herein.
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Page/Page column 23
(2012/08/07)
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- Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines
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Tert-Butyl cinnamates are aziridinated with high trans-selectivity by an N-N ylide generated in situ from N-methylmorpholine and O-diphenylphosphinyl hydroxylamine. The resulting N-unfunctionalised aziridines are shown to be versatile synthetic building b
- Armstrong, Alan,Ferguson, Alexandra
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p. 1747 - 1752,6
(2020/09/16)
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- Heterocycle synthesis via direct C-H/N-H coupling
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A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)2 oxidant, and toluene solvent at 80-120 °C. Cyclization is effective for sp2 as well as aliphatic and benzylic sp3 C-H bonds.
- Nadres, Enrico T.,Daugulis, Olafs
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supporting information; experimental part
p. 7 - 10
(2012/02/16)
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- C2-symmetric pyrrolidine-based chiral ammonium salts as a phase-transfer catalyst
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Chiral pyrrolidinium salts having substituents at the α, α' positions were synthesized to develop a chiral phase-transfer catalyst which have more simplified structure. The catalytic function of these synthesized catalysts was evaluated using asymmetric b
- Ishikawa, Tatsuya,Nagata, Kazuhiro,Kani, Sachiko,Matsuo, Mamoru,Sano, Daisuke,Kanemitsu, Takuya,Miyazaki, Michiko,Itoh, Takashi
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experimental part
p. 2577 - 2588
(2012/01/06)
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- A practical large-scale synthesis of cyclic RGD pentapeptides suitable for further functionalization through click' chemistry
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A multigram batch of the cyclo[Arg-Gly-Asp-d-Phe-Lys] and its N - azido derivative was accomplished via solution-phase synthesis using an epimerization-free fragment condensation. The C-terminus of d-Phe was protected as its tert-butyl ester. Fmoc (Arg, Gly, Asp, d-Phe) and Boc (Lys) groups were used to protect all N - termini. The Ts and NO2 groups, respectively were chosen to protect the guanidine group. The macrocyclization step (between d-Phe and l-Lys) was carried out under TBTU/HOBt or DPPA condensation conditions. Finally, the -amino group of the lysine residue was selectively converted into the azido group by a diazo-transfer reaction. Georg Thieme Verlag Stuttgart New York.
- Palecek, Jiri,Draeger, Gerald,Kirschning, Andreas
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experimental part
p. 653 - 661
(2011/04/15)
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- Small-molecule inhibitors of the TLR3/dsRNA complex
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The protein-RNA interface has been regarded as "undruggable" despite its importance in many biological processes. The toll-like receptor 3 (TLR3)/double-stranded RNA (dsRNA) complex provides an exciting target for a number of infectious diseases and cancers. We describe the development of a series of small-molecule probes that were shown to be competitive inhibitors of dsRNA binding to TLR3 with high affinity and specificity. In a multitude of assays, compound 4a was profiled as a potent antagonist to TLR3 signaling and also repressed the expression of downstream signaling pathways mediated by the TLR3/dsRNA complex, including TNF-α and IL-1β.
- Cheng, Kui,Wang, Xiaohui,Yin, Hang
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supporting information; experimental part
p. 3764 - 3767
(2011/06/18)
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- A bismuth(III)-catalyzed friedel-crafts cyclization and stereocontrolled organocatalytic approach to (-)-platensimycin
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A high yielding route to the (-)-platensimycin core is communicated. This entailed the discovery of Bi(OTf)3 to catalyze a Friedel-Crafts cyclization of a free lactol, supplemented by LiClO4 to suppress the Lewis basicity of the sulfonate group. After TBAF-promoted cyclodearomatization, a diastereoselective conjugate reduction of a dienone was achieved by adopting amine-based organocatalytic rationales to reverse the inherent steric control of the substrate.
- Eey, Stanley T.-C.,Lear, Martin J.
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supporting information; experimental part
p. 5510 - 5513
(2011/03/18)
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- Enzymatic synthesis of carnosine derivatives catalysed by Burkholderia cepacia lipase
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A new enzymatic synthesis of α,β-dipeptides has been developed with particular focus on the preparation of carnosine (β-alanyl-α-histidine) and analogues. The lipase PS-D from Burkholderia cepacia has been used as a catalyst for the formation of the pepti
- D'Arrigo, Paola,Kanerva, Liisa T.,Li, Xiang-Guo,Saraceno, Caterina,Servi, Stefano,Tessaro, Davide
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experimental part
p. 1641 - 1645
(2009/12/04)
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- PROCESS FOR PRODUCTION OF MONO-SUBSTITUTED ALKYLATED COMPOUND USING ALDIMINE OR DERIVATIVE THEREOF
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Disclosed is a process for producing an asymmetric mono-substituted alkylated compound of an α-amino acid which is represented by a specific formula by using an aldimine-type Schiff base. In the process, the alkylation of an aldimine-type Schiff base in a medium in the presence of an optically active quaternary ammonium salt phase transfer catalyst and an inorganic base is started, and subsequently the reaction is quenched at any time preceding the completion of the stoichimetrical reaction, thereby yielding a mono-substituted alkylated product having a high optical purity.
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Page/Page column 109
(2008/06/13)
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- Structure-selectivity studies on catalysts for the phase-transfer catalysed asymmetric alkylation of glycine imine esters
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In this paper, we describe the synthesis of a series of chiral quaternary ammonium salts with core structures that are closely related to the cinchona alkaloid, cinchonine. By employing these salts as asymmetric phase-transfer agents in the benzylation of a glycine imine, an optimal catalyst structure is identified.
- Lygo,Crosby,Lowdon,Wainwright
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p. 2391 - 2402
(2007/10/03)
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- Studies on the enantioselective synthesis of α-amino acids via asymmetric phase-transfer catalysis
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In this paper, we describe investigations into the use of cinchona alkaloid-derived quaternary ammonium phase-transfer catalysts for the asymmetric alkylation of a benzophenone-derived glycine-imine. Utility of this process is demonstrated by the enantioselective synthesis of a range of α-amino acid esters.
- Lygo,Crosby,Lowdon,Peterson,Wainwright
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p. 2403 - 2409
(2007/10/03)
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- Fatty acid analogs and prodrugs
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Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitrites thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which x is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5.
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- High molecular weight polymer-based prodrugs
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The present invention is directed compositions of the formula: STR1 wherein: D is a residue of biologically active moiety; X is an electron withdrawing group; Y and Y' are independently O or S; (n) is zero (0) or a positive integer, preferably from 1 to about 12; wherein: R1 and R2 are independently selected from the group consisting of H, C1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C1-6 alkyls; wherein: R3 is a substantially non-antigenic polymer, C1-12 straight or branched alkyl or substituted allyl, C5-8 cycloalkyl or substituted cycloalkyl, carboxyalkyl, carboalkoxy alkyl, dialkylaminoalkyl, phenylalkyl, phenylaryl or STR2 wherein: R4 and R5 are independently selected from the group consisting of H, C1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls, and substituted C1-6 alkyls or jointly form a cyclic C5 -C7 ring. In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.
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- High molecular weight polymer-based prodrugs
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The present invention is directed compositions of the formula: STR1 wherein: D is a biologically active moiety; X is an electron withdrawing group; Y and Y' are independently O or S; R1 is selected from the group consisting of H, C1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C1-6 alkyls; (n) is an integer from 1 to about 12; and R2 is a polyalkylene oxide. In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.
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- Enantioselective synthesis of α-amino acids from glycine t-butyl ester
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Enantioselective syntheses of optically active α-amino acids from glycine t-butyl ester through Schiff base employing (+)-N-alkyl-10-camphorsulfonamides as chiral auxiliaries were described. Methylation of Schiff base 5 gave high asymmetric inductions, whereas ethylation, allylation and benzylation gave fair asymmetric inductions. The stereochemistry of the major alkylation product was S configuration at the newly formed stereogenic center with the exception of the benzylation reaction in which the R configuration was generated.
- Yeh, Tsai-Lung,Liao, Chun-Chen,Uang, Biing-Jiun
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p. 11141 - 11152
(2007/10/03)
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- Fatty acid analogs and prodrugs
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Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L--Ala, L--Ile, L--Phe, L--Trp, L--Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5,
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- Chemoselective N-deprotection of tert-butyl 2-(trifluoroacetylamino) esters under PTC conditions: Synthesis of tert-butyl 2-aminocarboxylates
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Trifluoroacetamide 1 is alkylated in good yields (77-83%) by tert-butyl 2-bromocarboxylates 3 under solid-liquid phase transfer catalysis (PTC) conditions [anhydrous K2CO3, triethyl(benzyl)ammonium chloride (TEBA; 10%), MeCN, 80°C]. The resulting tert-butyl 2-(trifluoroacetylamino) carboxylates 5 are chemoselectively hydrolysed in 75-95% yields to the corresponding tert-butyl 2-amino carboxylates, isolated as hydrochlorides 8, under liquid-liquid PTC conditions [CH2Cl2 or Et2O, aqueous 20% KOH, TEBA (10%), 25-40°C].
- Albanese, Domenico,Corcella, Francesco,Landini, Dario,Maia, Angelamaria,Penso, Michele
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p. 247 - 249
(2007/10/03)
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- A new class of asymmetric phase-transfer catalysts derived from Cinchona alkaloids - Application in the enantioselective synthesis of α-amino acids
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A new class of Cinchona alkaloid-derived quaternary ammonium phase-transfer catalysts bearing a N-anthracenylmethyl function are presented. These catalysts show high stereocontrol in the asymmetric alkylation of a benzophenone-derived glycine-imine, and application of this process to the enantioselective synthesis of a range of α-amino acid esters (e.e. 67-94%) is investigated.
- Lygo, Barry,Wainwright, Philip G.
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p. 8595 - 8598
(2007/10/03)
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- An efficient preparation of the potent and selective pseudopeptide thrombin inhibitor, inogatran
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Inogatran is an effective and selective pseudopeptide inhibitor of thrombin that has been shown to be efficacious in a series of in vitro and in vivo models of thrombosis. Herein, we report an efficient and convergent chemical synthesis of Inogatran that is amenable to the preparation of multiple gram quantities.
- Preville, Patrice,He, John X.,Tarazi, Micheline,Siddiqui, M. Arshad,Cody, Wayne L.,Doherty, Annette M.
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p. 1563 - 1566
(2007/10/03)
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- Quinazoline antifolate thymidylate synthase inhibitors: γ-linked L-D, D- D, and D-L dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8- dideazafolic acid (ICI 198583)
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The syntheses of γ-linked L-D, D-D, and D-L dipeptide analogues of 2- desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) are described. The general methodology for the synthesis of these molecules involved the preparation of the dipeptide derivatives employing solution phase peptide synthesis followed by condensation of the dipeptide free bases with the appropriate pteroic acid analogue via diethyl cyanophosphoridate (DEPC) activation. In the final step, tert-butyl esters were removed by trifluoroacetic acid (TFA) hydrolysis. Z-L-Glu-OBu(t)-γ-D-Ala-OBu(t), for example, was prepared from α-tert-butyl N-(benzyloxycarbonyl)-L-glutamate and tert-butyl D-alaninate via isobutyl-mixed anhydride coupling. The Z- group was removed by catalytic hydrogenolysis and the resulting dipeptide free base condensed with 2-desamino-2-methyl-N10-propargyl-5,8- dideazapteroic acid via DEPC coupling. Finally, tert-butyl esters were removed by TFA hydrolysis to give ICI 198583-γ-D-Ala. The compounds were tested as inhibitors of thymidylate synthase and L1210 cell growth. Good enzyme and growth inhibitory activity were found with y-linked L-D dipeptides, the best examples being the Glu-γ-D-Glu derivative 35 (K(i) = 0.19 nM, L1210 IC50 = 0.20 ± 0.017 μM) and the Glu-γ-D-α-aminoadipate derivative 39 (K(i) = 0.12 nM, L1210 IC50 = 0.13 ± 0.063 μM). In addition, ICI 198583 L-γ-D-linked dipeptides were resistant to enzymatic degradation in mice.
- Bavetsias,Jackman,Kimbell,Gibson,Boyle,Bisset
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- ISOPROPENYL CHLOROCARBONATE (IPCC) IN AMINO ACID AND PEPTIDE CHEMISTRY: ESTERIFICATION OF N-PROTECTED AMINO ACIDS; APPLICATION TO THE SYNTHESIS OF THE DEPSIPEPTIDE VALINOMYCIN
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Esterification of N-protected α-amino acids was achieved via isopropenyl chlorocarbonate (IPCC) activation.In situ alcoholysis of the unstable mixed anhydride intermediate was catalised by 4-(dimethylamino)pyridine (DMAP).Competing isopropenyl ester formation was negligible when using methylene chloride as the solvent.A variety of esters from primary and secondary alcohols were obtained with good yields (60 to 90 percent), and even the more hindered tertiobutyl alcohol gave acceptable yields under more drastic conditions.The improvement in depsipeptide synthetic methodology is illustrated by preparation of the antibiotic valinomycin, using IPCC for ester bond formation, and BOP reagent for peptide coupling and the last-step cyclisation.
- Zeggaf, Choukri,Poncet, Joel,Jouin, Patrick,Dufour, Marie-Noelle,Castro, Bertrand
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p. 5039 - 5050
(2007/10/02)
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- Camphor-Derived Alcohols: An Anomalous Reaction of 3-Hydroxycamphor and the Influence of Internal Alkoxides on the Alkylation Stereochemistry of Glycinate Imines
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Attempted imine formation between 3-hydroxycamphor and tert. butyl glycinate led to 8, the substitution product at the 3-position.Zinc-acetic acid treatment of 8 afforded 3-acetoxycamphor.Alkylation of the imine from norcamphor and tert. butyl glycinate gave no stereoselection.Alkylation of the imine from 10-hydroxymethylcamphor and tert. butyl glycinate gave stereoselectivities inferior to those obtained from the imine of camphor itself (1), but aldol condensation with benzaldehyde, a reaction not possible with 1, was effected in 71percent yield.
- McIntosh, John M.,Cassidy, Kenneth C.,Matassa, Luca C.
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p. 5449 - 5458
(2007/10/02)
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- NEW SYNTHESIS OF DL-α-AMINOACIDS FROM t-BUTYL N(DIPHENYLMETHYLENE) OXAMATE
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The condensation of phosphorus ylids with t-butyl N(diphenylmethylene) oxamate gives 2-aza 1,3-dienes ; subsequent reduction with sodium cyanoborohydride provides protected α-aminoacids.
- Bazureau, J.P.,Person, D.,Corre, M. Le
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p. 3065 - 3068
(2007/10/02)
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- CONVENIENT ONE-POT ESTERIFICATION OF N-PROTECTED AMINOACIDS VIA ISOPROPENYL CHLOROFORMATE ACTIVATION.
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Activation of N-protected aminoacids by isopropenyl chloroformate leads to esters of primary, secondary and tertiary alcohols with 4-dimethylamino-pyridine as catalyst.
- Jouin, P.,Castro, B.,Zeggaf, C.,Pantaloni, A.,Senet, J.P.,et. al
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p. 1661 - 1664
(2007/10/02)
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- Alkylation of camphor imines of glycinates. Diastereoselectivity as a function of electronic factors in the alkylating agent
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Alkylation of the (R)-camphor imine of tert-butyl glycinate with a variety of alkylating agents gave diastereoselectivities ranging from 0-100percent.Simple alkyl halides larger than methyl give de's (diastereomeric excesses) of ca. 50percent whereas thos
- McIntosh, John M.,Mishra, Pratibha
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p. 726 - 731
(2007/10/02)
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