Yves Troin

Synthese stereospecifique par voie photochimique de trans hexahydro-1,2,3,4,4a,9a carbazolones-4 substituees en 4a1

Abstract Trans hexahydrocarbazol-4-ones substituted in 4a position were obtained quantitatively and stereospecifically by photocyclisation of tertiary aryl enaminones.

Photoreduction d'arylcetones par les amides et les lactames: applications synthetiques☆

Resume La benzophenone est photoreduite par les lactames et les amides. Dans cette reaction lhydrogene est arrache regioselectivement en α de latome dazote de la lactame, et le couplage des deux radicaux conduit a des adduits. La reaction est generale et equivalente a une hydroxyalkylation en α de lazote. Son rendement quantique est de 0.13 dans le cas de la N-methylpyrrolidone-2 dans CH 3 CH et dans C 6 H 6 . Les adduits derives de lacetopenone et de la p,p -dimethoxybenzophenone sont decrits. La reduction de ladduit 12 conduit a la diphenylethanolamine 22 et sa deshydradation a lenamide 21 .

Advances in tetrahydropyrido[1,2-a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors.

An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84xa0nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320xa0nM). Antiproliferative effects on cells were correlated with the inxa0vitro kinase activities and the best effects were obtained with lung and colon cell lines.

Convergent Approach to Tetracyclic [ABCE] Intermediates in Aspidosperma Alkaloids Synthesis

Abstract An efficient convergent synthesis of tetracyclic amidoalcohol 5, key intermediate in the synthesis of Aspidosperma alkaloids framework, starting from trans-hexahydrocarbazol-4-one 1 and substituted iodoacetamides 6 was achieved.

Une nouvelle reaction de photooxydation: transformation de lactames et d'amides en imides et hydroperoxydes☆

Irradiation of an oxygen-saturated solution of N-methyl 2-pyrrolidone in t-BuOH leads to N-methylsuccinimide. This reaction can be applied to other lactams and amides (2,3,12–16) and gives the corresponding imide. Lactams 27, 28 and 31 which are substituted α to the nitrogen atom give α hydroperoxy or α hydroxyamides 29, 30 and 32. The benzophenone triplet regioselectively abstracts the hydrogen atom α to the amide nitrogen to give radicals which are then oxidized. The decomposition mechanism of the peroxy radicals is discussed.

Stereoselective strategies for the construction of polysubstituted piperidinic compounds and their applications in natural products’ synthesis

Nitrogen-encompassing bioactive molecules can be regarded as the most frequently cited moieties, occurring either as natural products or as synthetically constructed chemical entities. One such framework which is abundantly found in both natural and synthetic chemical structures is the piperidinic core. A functionalized piperidinic core, either in natural products or in pharmaceuticals, is one of those immensely prevalent moieties. The piperidine frame can be seen in innumerable drug entities and this can be attributed to various reasons like the spacing obtained by piperidine structural conformers during the drug–receptor interactions, and solubility enhancement, hence resulting in improved pharmacokinetics and, most importantly, making the drug architecture metabolically stable. Further tapering down, 2, 4 and 6 substituted piperidines in general and with chiral centres in specific have attracted a substantial amount of attention in the recent past. This can be attributed to their diverse biological activities like analgesic, antimicrobial, sedative, antiasthmatic etc. In this communication, we aim to sum up and review all the reported methods since 2009 for the construction of the polysubstituted piperidinic core. Each method cited herein is exemplified with the synthesis of a natural compound and particularly alkaloids.

Novel optimization of valmerins (tetrahydropyrido[1,2-a]isoindolones) as potent dual CDK5/GSK3 inhibitors

An efficient synthetic strategy able to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton was developed. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally to support the SAR, a docking study was performed. A potent GSK3/CDK5 dual inhibitor (37, IC50 CDK5/GSK3 35/7 nM) was obtained. Best antiproliferative effects were obtained on lung and prostate cell lines with IC50 = 20 nM.

Systemes bicycliques azotes: une voie d'acces photochimique aux aza-1 bicyclo (n.2.0) alcanes substitues.

Abstract Photocyclisation of N-phenacyl and N-acetonyl lactams affords 1-azabicyclo (n.2.0) alkanes in good yields by a NORRISH type II reaction.