Henri-Philippe Husson

Production of indole alkaloids by in vitro root cultures from Catharanthus trichophyllus

Abstract Following in vitro infection of an aseptic Catharanthus trichophyllus plant with Agrobacterium rhizogenes (15834), six hairy root cultures were established. These were compared with normal root cultures, derived from the same plant, with respect to production of indole alkaloids. A rapidly growing hairy root line was used for fermenter (201) cultures. The alkaloid content of the roots obtained was examined. Seventeen monomeric indole alkaloids were purified and characterized, including five hitherto undescribed substances. Normal root and hairy root line cultures showed similar alkaloid composition. Analyses, performed at five-week intervals on five-week-old cultures showed variable alkaloid yields.

2-cyano Δ3 piperidines vi1 : a general method for the stereoselective synthesis of cis and trans 2,6-dialkylpiperidine alkaloids

The cis 2,6-dialkylpiperidine alkaloid (±) dihydro-pinidine 7b and the trans alkaloid (±) solenopsin A 5a were synthesized from a common α-aminonitrile synthon 1. The key step in this synthesis was the stereoselective reductive decyanation of the 1-benzyl-2cyano-2′, 6-dialkylpiperidines 3a and 3b.

Asymmetric synthesis III. Enantiospecific synthesis of the natural 3r, 5r, 9r (−) gephyrotoxin-223 AB

Abstract The first enantiospecific synthesis of the indolizidine alkaloid (−) gephyrotoxin-223 AB 2 has been achieved from the chiral 2-cyano-6-oxazolopiperidine synthon 3 .

EXPEDITIOUS FORMAL SYNTHESIS OF()-EPIBATIDINE USING DIASTEREOSELECTIVE BROMOHYDROXYLATION OF AMINOCYCLOHEXENE DERIVATIVES

Bromination and bromohydroxylation of oxazolidinones derived from cyclohexadiene have been studied in order to synthetize (±)-epibatidine 19. Bromohydroxylation of compound 2 led to a polyfunctionalized halohydrin 11a which could be further cyclized to azabicyclo[2.2.1]heptan-2-one 16 already described as a precursor of epibatidine 18.

Asymmetric synthesis of (R)- and (S)-piperidin-2-yl-phosphonic acid by diastereoselective addition of trialkyl phosphite onto potential iminium salt

Abstract Two strategies have been developed to synthesize both enantiomers of piperidin-2-yl-phosphonic acid. The first one uses the double condensation of glutaraldehyde with ( R )-(−)-phenylglycinol and triethylphosphite to give 2-ethylphosphonate-6-oxazolopiperidine 2 which furnished in few steps ( S )-(+)-piperidin-2yl-phosphonic acid ( 5 ) in 58% ee. The second strategy utilizes the 2-cyano-6-oxazolopiperidine synthon 1 which upon treatment with trimethyl phosphite gave 2-cyano-6-oxazaphosphorinane 7 which gave pure ( R )-(−)-piperidin-2-yl-phosphonic acid ( 10 ) in good overall yield.

A simple and general method for the asymmetric synthesis of α-aminophosphonic acids

Abstract A simple and general method for the asymmetric synthesis of α-aminophosphonic acids is described. A chiral phosphonate prepared in one step from R-(−)-phenylglycinol was alkylated with good diastereoselectivity using different electrophiles.

Diastereoselective bis-alkylation of chiral non-racemic α,β-unsaturated γ-lactams

Abstract A new chiral non-racemic γ-lactam 1 easily prepared in one step from ( R )-(−)-phenylglycinol was bis-alkylated α to the carbonyl function in very high to complete diastereoselectivity. The stereochemistry at the so-formed chiral quaternary center was ascertained through an X-ray crystallographic study.

Asymmetric synthesis XV : enantiospecific synthesis of (+) and (−) isonitramines from a common chiral intermediate

Abstract The enantiospecific synthesis of (+) and (−) isonitramines 7 has been achieved from a common chiral intermediate 5 ; this key compound was formed by condensation of two molar equivalents of glutaraldehyde with one mole of (−) phenylglycinol.

Simple 4-acetoxy-5,6-dihydropyridinium salts: New synthons for the preparation of functionalized piperidine systems

Abstract The simple 5,6-dihydropyridinium salt 2 (R 1 = CH 3 ′ R 2-5 = H) was prepared by reaction of the Δ 2 piperidone 1 (obtained from 3 ; 85% overall yield) with acetyl chloride at −50°C. Reaction of 2 with Grignard reagents gave the C-2 substituted products 6 a-f. Compound 6e was converted in three simple steps to the benzomorphan 12 .

Asymmetric synthesis IV. Preparation of chiral α-aminonitriles from a new N-cyanomethyl-1,3-oxazolidine synthon

The synthesis of (−)-N-Cyanomethyl-4-phenyl-1,3-oxazolidine 1 is reported. Good yields and moderate diastereomeric excesses (d.e.s.) of mono- and di-substituted α-aminonitriles were obtained from this simple chiral template.