- Enantioselective Synthesis of Quaternary α-Amino Acids Enabled by the Versatility of the Phenylselenonyl Group
-
A novel Cinchona alkaloid-catalyzed enantioselective conjugate addition of α-alkyl substituted α-nitroacetates to phenyl vinyl selenone was developed. The resulting enantio-enriched α,α-dialkyl substituted α-nitroacetates were subsequently converted to various cyclic and acyclic quaternary α-amino acids, taking advantage of the rich functionalities of the resulting Michael adducts. Novel protocols allowing chemoselective reduction of phenyl selenone to phenyl selenide and reduction of alkyl phenyl selenones to alkanes are also reported.
- Clemenceau, Antonin,Wang, Qian,Zhu, Jieping
-
supporting information
p. 18368 - 18372
(2016/12/16)
-
- Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
-
Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
- Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
-
p. 17869 - 17881
(2015/02/19)
-
- ISATIN AND OXINDOLE COMPOUNDS
-
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.
- -
-
Page/Page column 14
(2012/06/16)
-
- Highly enantioselective access to α-dibenzylamino ketones from chiral nonracemic α-bromo α′-sulfinyl ketones by dynamic kinetic resolution: Synthesis of (2R,1′S)-2-[1-(dibenzylamino)alkyl]oxiranes
-
A novel and efficient synthesis of enantiomerically pure α-dibenzylamino α′-sulfinyl ketones starting from a mixture of both epimers of α-bromo α′-(R)-sulfinyl ketone has been realized through combined in situ substitution-epimerization in a so-called Dynamic Kinetic Resolution (DKR). The scope of the reaction has been examined, and four differently substituted α-(S)-dibenzylamino α′-(R)- sulfinyl ketones were obtained in good yields with excellent diastereoselectivities. The utility of these derivatives was further illustrated with a highly stereoselective synthesis of syn-(2R,1′S)-2-(1- dibenzylaminoalkyl)oxiranes.
- Geant, Pierre-Yves,Martinez, Jean,Salom-Roig, Xavier J.
-
experimental part
p. 1300 - 1309
(2011/04/17)
-
- PYRIDONE GLUCOKINASE ACTIVATORS
-
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful
- -
-
Page/Page column 15
(2011/02/18)
-
- BCL-2-SELECTIVE APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE DISEASES
-
Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein.
- -
-
Page/Page column 251
(2010/06/20)
-
- PYRIDAZINONE GLUCOKINASE ACTIVATORS
-
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.
- -
-
Page/Page column 44-45
(2009/10/30)
-
- CATHEPSIN CYSTEINE PROTEASE INHIBITORS
-
This invention relates to class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis. They have the following structure: Formula (I).
- -
-
-
- Homologation of large rings
-
Free radical-promoted, one-carbon, ring expansion of twelve, fourteen-, and fifteen-membered cyclic β-keto esters is described. The method is then extended to include a three-carbon ring expansion of cyclododecanone, the targets being (±)-muscone and natu
- Dowd,Choi
-
p. 4773 - 4792
(2007/10/02)
-
- Synthesis of α-Phenylthio Enones and Esters of α-Phenylthio Alkenoic Acids
-
The title compounds can be made by a Pummerer dehydration from the corresponding saturated sulphoxides.The alkylation of anions from saturated and unsaturated ketones is described.
- Durman, John,Grayson, J.Ian,Hunt, Paul G.,Warren, Stuart
-
p. 1939 - 1946
(2007/10/02)
-
- ALKYLATION OF EXTENDED ENOLATES FROM α-PHENYLTHIO CROTONATE ESTERS
-
Conditions are described for the formation of enolate anions from substituted α-phenylthio-crotonate esters and their alkylation at the α-carbon atom.
- Durman, John,Hunt, Paul G.,Warren, Stuart
-
p. 2113 - 2116
(2007/10/02)
-
- Piperazinone and piperazine polypeptides
-
Piperazinone polypeptides which are useful as analgesics and psychotherapeutic agents as well as processes to produce them are described.
- -
-
-