Gérard Lhommet

Formal total synthesis of (+)-gephyrotoxin.

An efficient formal total synthesis of (+)-gephyrotoxin is described. The key step of our strategy relies on the diastereoselective reduction of a chiral pyrrolidine beta-enamino ester obtained by condensation of ( S)-phenylglycinol on a protected 8-hydroxy-3,6-dioxooctanoate.

Ant venom alkaloids from monomorium species : natural insecticides

Abstract 2,5-Disubstitued pyrrollnes have been isolated from Monomorium ant venom. Structural determination, synthesis and biological activity are described.

Synthesis of indolizidines (−)-195B, (−)-223AB and (−)-239AB: (2S,5R)-1-[(benzyloxy)carbonyl]-2-methoxycarbonyl-5-(4-pentenyl)pyrrolidine as a versatile chiral building block

Abstract The total syntheses of three levogyre 3,5-disubstituted indolizidines, (−)-195B, (−)-223AB and (−)-239AB are described. The employed strategy is based on the utilization of the common enantiopure trans 2,5-disubstituted pyrrolidine 3, which is assembled by addition of pent-4-enylcopper to N-acyl iminium ion derived from (S)-proline.

Highly Stereoselective trans Addition of π-Type Nucleophiles to a Bicyclic N-Acyliminium Ion – Application to the Synthesis of Indolizidine and Pyrrolizidine Alkaloids

Enantiopure bicyclic 5-ethoxytetrahydropyrrolo[1,2-c]oxazol-3-one 1b was prepared in two steps from the known tosylate 4, which is readily available from (S)-pyroglutamic acid. Trapping of the N-acyliminium ion (I), generated in situ from 1b in the presence of Lewis acid, with various silylated π-type nucleophiles gave rise selectively to trans adducts 2. The usefulness of this stereoselective access to trans-2,5-disubstituted pyrrolidines was illustrated by formal syntheses of 3,5-disubstituted indolizidine toxins, starting from 5-allyltetrahydropyrrolo[1,2-c]oxazol-3-one 2a. Moreover, an enantiodivergent synthesis of the pyrrolizidine alkaloids (+) and (–)-xenovenine was achieved starting from the same chiral building block 2a.

Enantioselective synthesis of (−)-gephyrotoxine 223AB [(3R,5R,9R)-3-butyl-5-propyloctahydroindolizine]

Abstract A highly enantioselective synthesis of the dendrobatid indolizidine alkaloid 223AB is described using a chiral amino acid as starting material.

Diastereocontrolled reduction of cyclic β-enaminones. A new diastereoselective route to 2,6-disubstituted piperidines

Abstract A new diastereoselective synthesis of 2,6-disubstituted piperidinic alkaloids is presented. Three natural compounds, the (−)-pinidinone 1a , the (+)-dihydropinidine 1b and the (−)-pinidinol 1c were prepared from optically pure (6 R )-6-methylpiperidin-2-one 2 . This method is based on the chemo- and diastereocontrolled reductions of an exocyclic β-enamino ketone.

New highly enantioselective synthesis of 6-alkylpiperidin-2-ones and 2-substituted piperidines

Abstract A versatile and highly enantioselective approach to 2-substituted piperidines is described using phenylglycinol as chiral auxiliary.

Enantioselective synthesis of (5R,9R)-5-propyl-octahydroindolizine [(−)-gephyrotoxin 167B]

Abstract A versatile and practical synthesis of the dendrobatid alkaloid 167B is described using a chiral amino acid as starting material.

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.

Chiral cyclic β-amino esters. Part I: Synthesis by diastereospecific alkylation

Abstract Chiral cyclic β-amino esters can be enantiospecifically prepared by a kinetically controled alkylation of the ester function of β-amino esters.