- C(sp3)?C(sp3) Bond Formation via Electrochemical Alkoxylation and Subsequent Lewis Acid Promoted Reactions
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A two-step transition metal-free methodology for the C(sp3)?C(sp3) functionalisation of saturated N-heterocyclic systems is disclosed. First, aminal derivatives are generated through the anodic oxidation of readily accessible carboxylic acids. Then, in the presence of BF3 ? OEt2, iminium ions are unmasked and rapidly alkylated by organozinc reagents under flow conditions. Secondary, tertiary and quaternary carbon centers have been successfully assembled using this methodology. Such an approach is especially relevant to drug discovery since it increases C(sp3)-functionalities rapidly within a molecular framework. As proof of concept, our methodology was applied to derivatization of peptides and an API. (Figure presented.).
- López, Enol,van Melis, Carlo,Martín, Raúl,Petti, Alessia,de la Hoz, Antonio,Díaz-Ortíz, ángel,Dobbs, Adrian P.,Lam, Kevin,Alcázar, Jesús
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supporting information
p. 4521 - 4525
(2021/08/06)
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- Electrochemical Scaled-up Synthesis of Cyclic Enecarbamates as Starting Materials for Medicinal Chemistry Relevant Building Bocks
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The electrochemical Shono oxidation of Boc-protected cyclic amines was revised. The conditions for scalable electrochemical synthesis of cyclic enecarbamates were found. The developed protocol included recycling of the full range of used reagents, favoring to E-factor reduction according to Green Chemistry requirements. The method opened the way for the convenient preparation of previously uncommon materials, which could become useful synthetic intermediates. Their synthetic potential was evaluated in [2+1] and [2+2] cycloadditions as well as electrophilic functionalization. Moreover, functionalized enecarbamates with carbonyl groups in β-position were used as latent 1,3-bielectrophiles in classical heterocyclizations. In a case of the hydrazine, the corresponding unusually decorated pyrazoles were prepared. The proposed methodology is a straightforward tool for the design and synthesis of Medicinal Chemistry relevant building blocks. As examples, 5-fluoro pipecolic and 3-fluoro isonipecotic acids were synthesized starting from Boc-protected esters of the pipecolic and the isonipecotic acids respectively; the 5-step approach to pyrazole containing α-aminoacids with different linkers between the aminoacidic and pyrazole moieties was elaborated based on the cheapest commercially available racemic and chiral cyclic α-aminoacids; the convenient approach to the functionalized tetrahydropyrido[3,4-d]pyridazines was proposed starting from Boc-protected ester of the isonipecotic acids. (Figure presented.).
- Tereshchenko, Oleksandr D.,Perebiynis, Maryana Y.,Knysh, Irina V.,Vasylets, Olesia V.,Sorochenko, Anna A.,Slobodyanyuk, Eugeniy Y.,Rusanov, Eduard B.,Borysov, Oleksandr V.,Kolotilov, Sergey V.,Ryabukhin, Sergey V.,Volochnyuk, Dmitriy M.
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supporting information
p. 3229 - 3242
(2020/07/06)
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- A Straightforward Synthesis of Six-Membered-Ring Heterocyclic α-Aminophosphonic Acids from N-Acyliminium Ions
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A convenient synthesis of phosphonic analogues of pipecolic acid and its heterocyclic analogues is reported. The major step of the elaborated procedure is the introduction of the phosphonate group into the skeleton of the appropriate cyclic amide through N-acyliminium ions. The former ones were obtained by preparation of the hemiaminals or their methyl ethers from the N-protected cyclic amides. Finally, the reaction with trimethyl phosphite in the presence of BF3·OEt2 afforded the desired phosphonates, which were converted into phosphonic acids by the hydrolysis of phosphonate moiety with simultaneous cleavage of the nitrogen protecting groups.
- Argüello-Velasco, Rubén Oswaldo,Sánchez-Mu?oz, Grecia Katherine,Viveros-Ceballos, José Luis,Ordó?ez, Mario,Kafarski, Pawel
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- Expedient preparation of nazlinine and a small library of indole alkaloids using flow electrochemistry as an enabling technology
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An expedient synthesis of the indole alkaloid nazlinine is reported. Judicious choice of flow electrochemistry as an enabling technology has permitted the rapid generation of a small library of unnatural relatives of this biologically active molecule. Furthermore, by conducting the key electrochemical Shono oxidation in a flow cell, the loading of electrolyte can be significantly reduced to 20 mol % while maintaining a stable, broadly applicable process.
- Kabeshov, Mikhail A.,Musio, Biagia,Murray, Philip R.D.,Browne, Duncan L.,Ley, Steven V.
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supporting information
p. 4618 - 4621
(2015/01/08)
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- Design, synthesis, antiviral activity, and structure-activity relationships (SARs) of two types of structurally novel phenanthroindo/quinolizidine analogues
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To investigate the influence of the variation of the original skeletons of natural phenanthroindo/quinolizidine alkaloids on antiviral activities, two types of structurally totally novel analogues 7a, 7b, 16a, and 16b were designed, synthesized, and evaluated against tobacco mosaic virus (TMV) for the first time. Bioassay results indicated that all four of the newly designed analogues showed good to excellent antiviral activities, among which analogue 16a dispalyed comparable activity with that of ningnanmycin, perhaps one of the most successful commercial antiviral agents, thus emerging as a potential inhibitor of plant virus and serving as a new lead for further optimization. Further structure-activity relationships are also discussed, demonstrating for the first time that the same changes of the original skeletons of phenanthroindolizidine and phenanthroquinolizidine exihibted totally different antiviral activities results, providing some original and useful information about the preferential conformation for maintaining high activities.
- Su, Bo,Chen, Fazhong,Wang, Lizhong,Wang, Qingmin
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p. 1233 - 1239
(2014/03/21)
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- Design, synthesis, antiviral activity, and structure-activity relationships (SARs) of two types of structurally novel phenanthroindo/quinolizidine analogues
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To investigate the influence of the variation of the original skeletons of natural phenanthroindo/quinolizidine alkaloids on antiviral activities, two types of structurally totally novel analogues 7a, 7b, 16a, and 16b were designed, synthesized, and evaluated against tobacco mosaic virus (TMV) for the first time. Bioassay results indicated that all four of the newly designed analogues showed good to excellent antiviral activities, among which analogue 16a dispalyed comparable activity with that of ningnanmycin, perhaps one of the most successful commercial antiviral agents, thus emerging as a potential inhibitor of plant virus and serving as a new lead for further optimization. Further structure-activity relationships are also discussed, demonstrating for the first time that the same changes of the original skeletons of phenanthroindolizidine and phenanthroquinolizidine exihibted totally different antiviral activities results, providing some original and useful information about the preferential conformation for maintaining high activities.
- Su, Bo,Chen, Fazhong,Wang, Lizhong,Wang, Qingmin
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p. 1233 - 1239
(2015/04/22)
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- Parallel electrosynthesis of N-acyliminium ion equivalents using silica gel-supported piperidine
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Parallel anodic methoxylation of carbamates was successfully carried out to provide the corresponding α-methoxylated products as N-acyliminium ion equivalents in high to excellent yields using silica gel-supported piperidine (Si-piperidine). Copyright
- Tajima, Toshiki,Nakajima, Atsushi
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experimental part
p. 160 - 161
(2010/02/16)
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- Aromatic organozinc reagents as nucleophiles in the α-arylation of piperidine and tetrahydropyran
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The arylation at the α-position of piperidine derivatives is achieved in good yield using aromatic organozinc reagents and either 2-methoxylated or α-cyanated piperidine. Oxygen-containing heterocycles such as 2-methoxy-tetrahydropyran reacts in a same manner to yield efficiently 2-arylated tetrahydropyran.
- Le Gall, Erwan,Gosmini, Corinne,Troupel, Michel
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p. 455 - 458
(2007/10/03)
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- Synthesis of new trialkylsilylmethyloxazinones via intramolecular trapping of β-silyl carbocations by an N-Boc group
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N-BoC amino ethers 1a-e when treated with allyltrialkylsilanes in the presence of TiCl4 afford the expected allylation compounds 2a-e and/or the unprecedented silylated oxazinones 3a-e or 4a-e.
- Brocherieux-Lanoy, Sylvie,Dhimane, Hamid,Poupon, Jean-Christophe,Vanucci, Corinne,Lhommet, Gerard
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p. 2163 - 2165
(2007/10/03)
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