C3′-cis-Substituted carboxycyclopropyl glycines as metabotropic glutamate 2/3 receptor agonists: Synthesis and SAR studies

González, R.; Collado, Iván; Uralde, Beatriz López de; Marcos, Alicia; Martín-Cabrejas, Luisa M.; Pedregal, Concepciòn; Blanco‐Urgoiti, Jaime; Pérez‐Castells, Javier; Fernández, María; Andis, Sherri L.; Johnson, Bryan G.; Wright, Rebecca A.; Schoepp, Darryle D.; Monn, James A.

doi:10.1016/j.bmc.2005.07.036

Cited by 11 publications

(12 citation statements)

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“… 48 Elongated reaction times were needed (DBU, CHCl 3 , r.t., overnight, 82% yield), however, when a bicyclic framework was constructed from cyclopentenone 1a with the less nucleophilic sulfonium ylide derived from ethyl (dimethylsulfonium)acetate bromide ( N / s N = 15.9/0.61 in DMSO). 49 …”

Section: Resultsmentioning

confidence: 99%

“…48 Elongated reaction times were needed (DBU, CHCl3, overnight, r.t., 82% yield), however, when a bicyclic framework was constructed from cyclopentenone 1a with the less nucleophilic sulfonium ylide derived from ethyl (dimethylsulfonium)acetate bromide (N/sN = 15.9/0.61 in DMSO). 49 With the same sulfonium ylide as the nucleophile, the butenolide 4a (E = -20.7) was reported to produce only a poor yield (22%) of the attempted cyclopropanation product (Cs2CO3, DMF, r.t., reaction time not given). 50 Conjugate additions of silyl ketene acetals (N/sN = 9.0/0.98 in CH2Cl2 for Me2C=C(OMe)OSiMe3) to 4a and 5,6-dihydro-2H-pyran-2-one 5a (E = -21.8) required activation e.g.…”

Section: Application Of Electrophilicity Parameters In Synthesismentioning

confidence: 99%

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Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Section: Application Of Electrophilicity Parameters In Synthesismentioning

confidence: 99%

Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

et al. 2021

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“…The synthetic strategy was based on the cyclopropanation of cyclopentenone 6 with ethyl-(dimethylsulfuranylidene)-acetate (EDSA), generated in situ from the corresponding sulfonium bromide 7 and DBU in CHCI 3 at r.t. ( Fig 6 ). [ 20 ] , [ 21 ] The cyclopropane 8 was obtained as a racemic mixture in 85% yield. The second double bond was introduced in the five-membered ring in 78% yield by transforming the ketone in the corresponding silylenolether (LHMDS, TMSCl), which was then oxidized to the enone 9 with Pd(OAc) 2 .…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of constrained bicyclic molecules as candidate inhibitors of influenza A neuraminidase

et al. 2018

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The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (NA; sialidase) active site. Given that our first series of compounds were at least four orders of magnitude less active than available drugs, we hypothesized that the new carbon skeleton did not elicit the same interactions as the cyclohexene frameworks used previously. Herein, we tried to address this critical point with the aid of molecular modeling and we proposed new structures with different functionalization, such as the introduction of free ammonium and guanidinium groups and ether side chains other than the 3-pentyl side chain, the characteristic side chain in Oseltamivir. A highly simplified synthetic route was developed, starting from the cyclopropanation of cyclopentenone and followed by an aziridination and further functionalization of the five-member ring. This allowed the efficient preparation of a small library of new bicyclic ligands that were characterized by enzyme inhibition assays against influenza A neuraminidases N1, its H274Y mutant, and N2. The results show that none of the new structural variants synthesized, including those containing guanidinium groups rather than free ammonium ions, displayed activity against influenza A neuraminidases at concentrations less than 2 mM. We conclude that the choice and positioning of functional groups on the bicyclo[3.1.0]hexyl system still need to be properly tuned for producing complementary interactions within the catalytic site.

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“…Additional procedures for the synthesis of analogous pyroglutamates are disclosed in the literature,84 although their suitability for the preparation of 3,4‐methanoproline derivatives has not been explored. For example, the preparation of 209 and 210 involved rhodium‐catalysed cyclopropanation of 205 with ethyl diazoacetate (Scheme ) 84a,84b. The cleavage of the acetal group provided a diol that was oxidized to hemiketal 206 .…”

Section: Synthesis Of Three‐membered‐ring [C]‐fused Proline Analoguesmentioning

confidence: 99%

Synthesis of [c]‐Fused Bicyclic Proline Analogues

et al. 2015

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An overview of synthetic methods developed to build [c]‐fused bicyclic proline analogues is presented. The focus is on the preparation of azabicycles that bear a carbocyclic ring fused to the [c] face of the pyrrolidine unit. Attention is paid both to procedures that afford the desired compounds in racemic form and to asymmetric strategies. Procedures are organized according to the size of the carbocycle that is fused to the pyrrolidine moiety. Strategies able to provide multigram quantities of enantiopure compounds that have application in the synthesis of marketed drugs are highlighted.

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C3′-cis-Substituted carboxycyclopropyl glycines as metabotropic glutamate 2/3 receptor agonists: Synthesis and SAR studies

Cited by 11 publications

References 50 publications

Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

Design and synthesis of constrained bicyclic molecules as candidate inhibitors of influenza A neuraminidase

Synthesis of [c]‐Fused Bicyclic Proline Analogues

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