Martine Bonin

ASYMMETRIC 1,3-DIPOLAR CYCLOADDITIONS OF A CHIRAL NON-RACEMIC AZOMETHINE IMINE

Abstract Chiral non racemic carbazate 1 , derived from ( R )-(−)-phenylglycinol, reacts regioselectively with benzaldehyde or its dimethylacetal to give an azomethine imine. The facial, endo exo and regio selectivities of 1,3-dipolar cycloadditions of this reactive species with various dipolarophiles have been studied and are described in this paper. In the best cases, up to three contiguous asymmetric centers could be generated simultaneously, in a complete enantio- and diastereoselective fashion.

Total Enantioselective Synthesis and In Vivo Biological Evaluation of a Novel Fluorescent BODIPY α‐Galactosylceramide

Natural killer T (NKT) cells are a distinct subset of mature lymphocytes endowed with features of activated and regulatory T cells. α‐Galactosylceramides (α‐GalCers), the synthetic prototype of which is KRN7000, are the only natural reagents recognised by the T‐cell receptor of NKT cells. The α‐GalCer‐activated NKT cells promptly release IFNγ and IL‐4 (IFN=interferon; IL=interleukin) and undergo apoptotic death within hours. In mice, activated NKT cells are responsible for antitumour activity and protection against autoimmune diseases. KRN7000 can thus be considered as the root of a family of novel immunoregulatory drugs. To get insights into the in vivo behaviour of α‐galactosylceramides, an original fluorescent derivative has been prepared by following a convergent synthetic scheme. This strategy allows the introduction of different acyl chains, carbohydrate residues and various labels in the final steps of the synthesis. The fluorescent BODIPY probe derived from a versatile glycolipid precursor is as active as KRN7000 for inducing apoptosis of liver NKT cells. Fluorescence was detected in peritoneal macrophages and splenic antigen‐presenting cells, in Kupffer‐like cells in the liver, but not in lymphocytes.

STEREOSELECTIVE SYNTHESIS OF 2,6-DISUBSTITUTED MORPHOLINES FROM CHIRAL NON-RACEMIC LACTAMS

Abstract Optically pure 2,6-disubstituted morpholines 11 have been obtained by diastereoselective alkylation of 6-substituted 3-oxo morpholines 1 derived from ( R )-(−)-phenylglycinol and a series of chiral epoxides.

The Origin of Chemical and Configurational Stability of Chiral Nonracemic tert-Butyl Aziridinecarboxylate Anions

The origin of good chemical and configurational stability of aziridine ester anions derived from (R)-(−)-phenylglycinol has been investigated. Kinetic acidity seems to play an important role in the deprotonation step and chemical stability of the anionic species. Spectroscopic investigations showed that the good overall retention of configuration was governed by the directing effect of the nitrogen atom, which acts as a stereogenic centre in the alkylation step of the enolate intermediate.

Diastereoselective alkynylation of chiral non-racemic oxazolidines with mixed organoaluminum compounds

Abstract A new efficient and scalable route to chiral non-racemic α-substituted propargylamines is described. The reaction pathway consists of the diastereoselective addition of mixed alkynylaluminum reagents to oxazolidines derived from R-(−)-phenylglycinol.

Asymmetric synthesis of (+) and (−) trans-2,6-dimethylpiperidines

Abstract (+) and (−) trans-2,6-dimethylpiperidines 9 have been prepared from diastereomeric lactams 6 and 11, both available from (R)-(−)-phenylglycinol 4. Diastereoselective C-2 alkylation afforded oxazolidines 7 and 12. Reduction of 7 with LiAlH4 or NaBH4 led to trans-2,6-8 with total retention of configuration. When 12 was reduced with NaBH4, trans derivative 13a was isolated as the major isomer. A mechanism is proposed to explain the different results.

[2,3]-Meisenheimer rearrangement of N-allyl phenylglycinol derivatives. NC versus CC chirality transfer

Abstract The [2,3]-Meisenheimer rearrangement has been investigated on various allylic amines bearing phenylglycinol as a chiral appendage. The relative importance of NC and CC chirality transfer is discussed.

Asymmetric synthesis. XXXIX.1 Synthesis of 3-substituted piperidin-2-ones from chiral non-racemic lactams

Abstract A series of 3-substituted piperidines in enantiomerically pure form has been synthesized from lactam 1 via the bromo derivative 2i. t-Butyl acetate and 5-methylpyridine derivatives 2g and 2h were obtained optically pure by direct alkylation of 1 with corresponding halides. Azido, amino or benzyloxy products were obtained by diastereoselective substitution of 2i.

Practical preparation and substitution of configurationally stable aziridinyl ester anions

Abstract Configurationally and chemically stable aziridine carboxylate anions have been generated. These intermediates are stable at −78°C for several hours and react with electrophiles with good to excellent retention of configuration.

Diazaborolidines, a new class of enantioselective organoboron catalytic agents.

Abstract Diazaborolidines 6 and 9, derived from 2-aminomethyl-piperidine, have been prepared in an optically pure form from 2-cyano-6-phenyl oxazolopiperidine 3. The best results for the asymmetric reduction of acetophenone (yield>95%, 72% ee) have been obtained with BH3.Me2S in the presence of 9a as a chiral catalyst.