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I. I. Chapitre, Synthèse de nouveaux hétérocycles fonctionnels types 1,3-Imidazoldin-2-ones à partir d'aziridine-2-carboxylates diversement substituées 119

, Experimental Part Chapitre II: Synthèse de nouveaux hétérocycles fonctionnels types 1,3-Imidazoldin-2-ones à partir d'aziridine-2-carboxylates diversement substituées

I. Chapitre, Stratégie de synthèse de (S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir d'oxazolidines trifluorométhylées chirales Schéma, p.19

, La deuxième voie (voie B) fait intervenir comme étape clé, la cyclisation via un mésy-late des (R)-et (S)-?-Tfm-sérines 16 dont la synthèse a été préalablement décrite dans notre laboratoire, Cette méthode repose essentiellement sur des protections sélec-tives réalisées sur les (R) et (S)-?-Tfm-sérines, vol.54

, Schéma, vol.20

. L'étape-clé-de-la-troisième-stratégie-envisagée, Voie C) est une réaction de Strecker effectuée sur l'oxazolidine O-mésylée 12 pour donner les ?-aminonitriles 13 correspondants. La cyclisation intramoléculaire de ces aminonitriles en aziridines suivie de l'hydrolyse de la fonction nitrile et la débenzylation de la chaîne phénylglycinol doit constituer une voie d'accès rapide aux ?

, Schéma 21

I. Chapitre, Stratégie de synthèse de (S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir d'oxazolidines trifluorométhylées chirales

, ? Des essais de saponifications dans des conditions basiques (KOH, NaOH) ont été testés sur ces composés, mais malheureusement, ils ont échoués

. ?-l', hydrogénolyse de l'aminoacide 21 catalysée par le Pd/C n'a malheureusement pas permis non plus d'obtenir l'aminoacide cible complétement déprotégé

, Troisième voie de synthèse d'aziridine-2-carboxyliques

, La stratégie de synthèse décrite précédemment n'est pas pleinement satisfaisante puisque les deux groupes protecteurs benzyles et ne sont pas orthogonaux. C'est la raison pour laquelle nous avons proposé une troisième stratégie qui s'effectue selon la séquence activationStrecker-substitution

, Notre laboratoire dispose d'une stratégie élégante et simple d'accès à un mélange de morpholinones intermédiaires résultat d'une cyclisation sélective d'?-aminonitriles diastéréoisomères dans des conditions acides. Ces morpholinones peuvent ensuite être, séparées par chromatographie, permettant l'obtention respectivement des acides (R) et (S)-?-Tfm-Aspartique

I. Chapitre, Stratégie de synthèse de (S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir d'oxazolidines trifluorométhylées chirales Liste de références

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I. Chapitre, Stratégie de synthèse de (S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir d'oxazolidines trifluorométhylées chirales

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I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

H. Nmr, 00 MHz), 13 C NMR (100.50 MHz) and 19 F (376.20 downfield from C6F6 as internal standard

, µm.) silica gel, employing mixture of specified solvent as eluent. Thin-layer chromatography (TLC) was performed on Merck silica gel (Merck 60 PF254) plates. Silica TLC plates were visualized under UV light, by a 10% solution of phosphomolybdic acid in ethanol followed by heating. Mass spectra (MS), Coupling constants are reported in Hertz. Column chromatography was performed on SDS 60A, pp.40-63

, MSD with an HP 6890 series GC. Ionization was obtained by electronic impact (EI 70 eV)

, Melting Points were measured on a Büchi apparatus and uncorrected. IV.2. General procedures and product descriptions Path A Preparation, Infrared spectra (IR) were obtained by Fourier-transformation on BRUCKER TENSOR 27, wavenumbers are given in cm -1 . Optical rotations were determined using a JASCO P1010 polarimetry. HRMS analyses were performed on a Joel JMS-GC Mate II and on a waters LCT premier XE, KE 483

, Phenylglycinol (50.0 g, 365.0 mmol, 1 equiv) in THF (700 mL) at 0°C was added Et3N (40.55 g, 401.5 mmol, 1.1 equiv) and Boc2O (87.52 g, 402.0 mmol, vol.1

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

C. Nmr,

R. , mmol, 1.0 equiv) in toluene (800 mL) at room temperature, were added pyridinium p-toluenesulfonate (4.7 g, 18.9mmol, 0.15 equiv) and ethyl trifluoropyruvate (18.4 mL, 139room temperature, refluxed with a Dean-Stark apparatus for 5 h, and then cooled to 0 °C with an ice-bath. The resulting mixture was filtered and toluene was evaporated to afford the corresponding oxazolidine (70:30 diastereomeric mixture) 10. The crude productwas used without further purification

H. Nmr, MHz, issue.400

, Chapitre III: Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, 103 Anal Calc. C, 53.98

, To a 70:30dr mixture of oxazolidine 10 (9.45 g, 32.7 mmol, 1.0 equiv) in methanol

, 4R)-2-Hydroxymethyl-2-trifluoromethyl-4-phenyl-1,3-oxazolidine 11maj: White solid; mp 156°C

, H NMR (400 MHz, CDCl3) ?: 3.79 (d, J=12.1 Hz, 1H), 4.00 (d, J=12.1 Hz, 1H), 4.42 (t, J=7.4 Hz, 1H), 4.61 (dd, J=7.4 Hz and 6.6 Hz, 1H), vol.1, pp.53-97

, (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales 11min: Colorless oil

. Hz,

. Hz, 124.0 (q, J=288.5 Hz), vol.126

. Anal,

, To a 70:30 dr mixture of oxazolidine hydroxyle 11 (2.009 g, 8.12 mmol, 1.0 equiv) in

, The reaction was stirred for 1 hour at room temperature, and then quenched with water (100 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×30 mL). The combined organic extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. After filtration through a short pad of silica gel, the O-mesylatedoxazolidinone 12 was obtained as 70:30 diastereoismeric mixtures as a yellow oil

, Yellow oil, Rf= 0.45 (70:30 cyclohexane/ethyl acetate), Compound, vol.12

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales of (S)-13. (2R, 5S

, 13: Yield 82%; White solid; mp 48°C

, CHCl3

H. Nmr, MHz, CDCl3) ?: 2.22 (d,J=1.7 Hz,1H), 2.24 (d, J=1.7 Hz, 1H), 3.73 (t, J=9.9, 1H), 4.63 (dd, J=9.9 and 8.0 Hz, 1H), 4.72 (dd, J=9.9 and 8.0 Hz, 1H)

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales (2R, 5R

, CHCl3); 1 H NMR (400 MHz, CDCl3) ? 2.31 (d,J=2.1 Hz, 1H), vol.2

, 00 g, 8.1 mmol, 1 equiv) in with brine (20 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by flash chromatography (80:20 cyclohexane/ethyl acetate) gave 1.03 g (46%) of a pure fraction of the (S)-14, 510 mg (23%) of mixture of both diastereoisomer and 630 mg (28%) of a pure fraction of the minor diastereoisomer (R)-14, dr mixture of hydroxymethyl oxazolidine 11, p.30

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, Compound (R)-14: Yield 28%; White solid; mp 78°C

, = -83.3 (c 1.0, CHCl3)

, H NMR (400 MHz, CDCl3) ?: 3.00 (br s,3H), 3.60 (dd, J=11.2 Hz, 8.7 Hz, 1H), vol.3250, pp.52-56

N. , , vol.87

, Compound (S)-14: Yield 46%; White solid; mp 59°C

, CHCl3

, CDCl3) ?: 2.6 (br s,3H), 3.52 (dd, J=12.2 Hz and 8.8 Hz, 1H), 3.75 ( m, 3H), pp.52-56

, Preparation of (R)-?-trifluoromethylserine A solution of aminonitrile (S)-14 (1.46 g, 5.3 mmol, 1.0 equiv) in concentrated HCl (40 mL) was heated at reflux overnight, and then concentrated under reduced pressure. The crude hydrochloride ammonium salt of (?)-trifluoromethylserine was then washed with diethyl ether to give, after filtration, the (R)-(?)-trifluoromethylserine hydrochloride as a white solid

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

H. Nmr,

. Hrms-(ei, , pp.4-7

, The crude hydrochloride ammonium salt of (R)-(?)-trifluoromethylserine was then loaded into DOWEX 50W8-400 resin to afford 636 mg (75%) of the crude (R)-?-Tfm serine, p.16

, White solid

, R)-2-Amino-3-trifluoromethyl-2-(hydroxymethyl) propanoic acid Preparation of (S)-?-trifluoromethylserine, p.16

, equiv) in concentrated HCl (40mL) was warmed to reflux overnight, and then concentrated under reduced pressure. The crude hydrochloride ammonium salt of (?)-trifluoromethylserine was then washed with diethyl ether and then loaded into DOWEX 50W8-400 to afford 544 mg (94%) of the pure (S)-?-trifluoromethylserine(S)-16, A solution of aminonitrile(R)-14 (935 mg

, S)-2-Amino-3-trifluoromethyl-2-(hydroxymethyl) propanoic acid hydrochloride

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, To a solution of (R)-15 (0.410 g, 1.9 mmol, 1 equiv) in DMF (5 mL) was added PhCH2Br

, The resulting mixture was stirred at room temperature for 2 hours (TLC and 19 F NMR monitoring) and quenched with water (30 mL). The organic layer was separated and the resulting aqueous phase was extracted with AcOEt (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gradient chromatography (gradient 90:10 to 70:30 cyclohexane/ethyl acetate) to give (R)-17

, CDCl3): ? -73.9 (s). HRMS calcd for C18H19F3NO3 354.1303 found 354.1317. (R)-18: Yellow oil, Hz, 1H), 3.98 (d, J=11.5 Hz, 1H), 4.09 (d, J=11.5 Hz, 1H), 5.29 (s, 2H) 7.25-7.37 (m, 10H); 13 C NMR (100.5 MHz, CDCl3) ?: 47.9, vol.123

C. Mhz, (s). HRMS (EI) calcd for C11H13F3NO3

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, To a solution of (S)-15 (0.402 g, 1.9 mmol, 1 equiv) in DMF (5 mL) was added PhCH2Br

, g, 3.8 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 hours (TLC and 19 F NMR monitoring) and quenched with water (30 mL). The organic layer was separated and the resulting aqueous phase was extracted with AcOEt (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gradient chromatography, vol.70, p.30

, cyclohexane/ethyl acetate) to give (S)-17 (0.380 g, 57 %) and (S)-18 (0.150 g, 30%). (S)-17: White solid, pp.112-113

, HRMS calcd for

, The other spectroscopic data of (S)-17 and (S)-18 were similar to those of (R)-17 and (R)-18 respectively, HRMS calcd for

, 2 equiv) was slowly added at 0°C to a stirred solution of (R)-17 (0.216 g, 0.61 mmol, 1 equiv) and triethylamine (0.33 ml, 2.4 mmol, 4 equiv) with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography

, (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales (R)-20: Colorless oil

, CHCl3

, 13 C NMR (100.5 MHz, CDCl3): ? 37, vol.6

. Hz,

, HRMS (EI) calcd for C19H21F3NO5S 432.1082 found 432.1090. (R)-2-benzylamino-2-trifluoromethyl-3-methylsulfonylbenzylpropanoate

, Methanesulfonyl chloride (0.09 mL, 1.1 mmol, 2 equiv) was slowly added at 0°C to a stirred solution of (S)-17 (0.200 g, 0.57 mmol, 1 equiv)

, After complete consumption of starting material, the solution was quenched with saturated NH4Cl aqueous solution (50 mL). The organic layer was separated and the resulting aqueous phase was extracted using CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography

, CHCl3

, The other spectroscopic data of (S)-20 were similar to those of (R)-20, HRMS calcd for

, Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales Preparation of trifluorometylated aziridine-2-carboxylates To a solution of (R)-20-(0.100 g, 0.23 mmol, 1 equiv) in CH3CN (10 mL) was added

, H NMR (400 MHz, CDCl3) ?: 2.45 (bs, 1H), vol.1, pp.1735-1736

, 13 C NMR (100.5 MHz, CDCl3) ? 37.7, 44.2 (q, J=24.0 Hz), 55.7, 67.9, vol.122

, HRMS (EI) calcd for C18H17F3NO2 336.1208 found 336.1211. (R)-N-benzyl-2-benzyloxycarbonyl-2-trifluoromethylaziridine

, g, 0.21 mmol, 1 equiv) in CH3CN give (S)-21 (0.055 g, 79 %) as colorless oil

, HRMS calcd for C18H17F3NO2 336.1205 found 336.1211. The other spectroscopic data of (S)-21 were similar to those of (R)-21

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales -86

H. Nmr, MHz, CDCl3) ? 2.47 (br s, 1H, OH or NH),2.90 (br s,3H), vol.3345, pp.2356-2357

. Hz,

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, Compound (R)-21: Yield 36%; White solid; mp 125°C; Rf=0.70 (70:30 cyclohexane/ethyl acetate)

, H NMR (400 MHz, CDCl3) ?2.47 (br s, 1H), vol.3345, pp.2361-2362

. Mhz, HRMS (EI) Calcd for C13H16F3N2O4S

, To a solution of aminonitrile (R)-22 (400 mg, 1.14 mmol, 1.0 equiv) was added 0, vol.91

, AcOH (15.89 mmol, 14 equiv) at room temperature then the mixture was refluxed for 24

, The reaction was cooled down to room temperature and carefully neutralized with a saturated solution of NaHCO3 and extracted with AcOEt (3×10 mL). The combined organic extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude was then purified by silica gel chromatography with an elution gradient, The reaction was monitored by TLC, vol.80, p.23

, N-(phenylethylacetate) -2-cyano-2-trifluoromethyl aziridine

, Yield: 71%;White oil, Compound, vol.23

, CHCl3

, cm -1 ; 1 H NMR (400 MHz, CDCl3) ? 2.00 (s, 1H), 2.15 (s, 3H), Chapitre III: Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales, p.2250, 1743.

, 0 equiv) in acetonitrile (15 mL) to reflux for 48 hours. The reaction was monitored by TLC (70:30 NH4Cl (50 mL) and extracted with AcOEt (3×20 mL). The combined organic extracts were washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude was then purified by silica gel chromatography with an elution gradient (80:20 and 70:30 cyclohexane/ethyl acetate) to give (R)-24 (0.347 g, 72%) as pure isolated compounds. (2R, 6R)-2-phenyl-6-trifluoromethyl-4-oxa-1-azabicyclo

, CHCl3

, H NMR (400 MHz, CDCl3) ?: 2.49 (brs, 1H,), 2.69 (brs, 1H), vol.1, pp.1729-1730

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, To a solution of aminonitrile (R)-22 (590 mg, 1.67 mmol, 1.0 equiv) in acetonitrile

, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was then purified by silica gel chromatography with an elution gradient (80:20 to 70:30 cyclohexane/ethyl acetate) to give (S)-25 (0.393 g, 91%) as pure isolated compounds

, Yield: 91%; White oil, Compound, vol.25

, Hz, 1H), 3.94 (dd, J=11.4 Hz and7.8 Hz, 1H)

. Mhz, HRMS (EI) Calcd for C12H12F3N2O [M+H] + 257.0909, Found 257.0902. Preparation of aziridines carboxylic acid To a solution of aziridines 25

, The solution was stirredfor 40hours under reflux. The reaction was cooled to room temperature and the crude mixture was washed with a solution of HCl (1N) (20 mL) and extracted with AcOEt (2×50 mL). The combined organic extracts were washed with brine (50 mL), dried over Chapitre III: Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales (2S)-N-((1R)-phenyl-2-hydroxy-ethyl)-2-trifluoromethylaziridine-2-carboxylic acid Compound 26: Yield: 88%; White solid, /1) (15 mL), was added LiOH (0.185, 7.71mmol, 2equiv) at room temperature

, 66 (br s, 1H), 2.69 (br s, 1H), 3.63-3.84 (m, 3H), 7.23-7.37 (m, 5H), H NMR (400 MHz, D2O) ?: 1.96 (br s, 1H, OH), vol.1, p.26

, The resulting mixture was stirred at 48°C for 10 hours (TLC and 19 F RMN monitoring). The solution was then concentrated under vacum quenched with cold water (10 mL). The resulting aqueous mixture was extracted using AcOEt (2×10 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (70:30 cyclohexane/ethyl acetate) to give (S)-27 (108 mg, 70%) as pure isolated compound

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, Yield: 70%; Viscous oil, Compound, vol.27

. Mhz, CDCl3) ?: -72.8 (s, 3F, CF3)

, 26 (54 mg, 0.20mmol, 1 equiv) in 5 mL of methanol was added Pd(OH)2 10% (54 mg, 1 equiv, w/w). The resulting mixture was stirred under 5 bars atmosphere of H2 for 96 hours (TLC and 19 F RMN monitoring). The solvent was remouved under reduced pressure and the resulting crude was

, The organic extracts are discarded and the resulting mixture is diluted with HCl (1N) (2×10 mL) and the Pd(OH)2 was filtered off using a PP chromafil®. The HCl was evaporated to give pure (S)-28 (11 mg, vol.29

, 2S)-2-amino-3-chloro-2-trifluoromethyl propanoicacid

I. Chapitre, Stratégie de synthèse de(S)-& (R)-Tfm Aminoacides cycliques type aziridiniques à partir D'oxazolidinestrifluorométhylées chirales

, Coupling reaction of aziridines carboxylic acid with L-alanine tert-butyl ester hydrochloride HCl

, To a solution of aziridines carboxylic acid 26 (209 mg, 0.76 mmol, 1.0 equiv) in tetrahydrofurane (10 mL), were successively added L-alanine tert

, mL, 2.28 mmol, 3 equiv) and after 15 minutes stirring at room temperature BOP-Cl (0.386 g, 1.52 mmol, 2 equiv). The reaction mixture was stirred overnight at room temperature, and then quenched with water (20 mL). The layers were separated and the aqueous phase was extracted with AcOEt

, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was then purified by silica gel chromatography with an elution gradient (80:20 and 70:30 cyclohexane/ethyl acetate) to give (S)-29 (244 mg, 80%) as pure isolated compounds. (2S)-N-((1R)-phenyl-2-hydroxy-ethyl, The combined organic layers were washed with brine (20 mL)

, Yield: 80%; Viscous oil, Compound, vol.29

, Hz, 3H), 1.39 (br s, 1H),2.15 (br s, 1H, OH), 2.53 (br s, 1H), 2.74 (s, 1H),3.52 (br s, 1H), H NMR (400 MHz, CDCl3) ?: 0.86 (d, J=6.1, vol.1, pp.1671-1672, 1733.

, Hydrogenolyse of dipeptide To a solution of dipeptide (S)-29 (186 mg, 0.46 mmol, 1.0 equiv) in MeOH (5 mL) was

, After completion, the mixture was directly filtered off cotton and celite and the solvent was removed under reduced pressure and the resulting crude product was purified by silica gel chromatography (90:10 cyclohexane/ethyl acetate) to give (S)-30 (0.066 g, 51%) as white solid

, Yield: 51%; white solid, Compound, vol.30

, 1.50 (s, 18H), 1.97 (brs, 1H), 2.16 (brs, 1H), 2.29 (brs, 1H), vol.2

, Conclusion Générale

, Après hydrolyse acide, une protection sélective des deux fonctions acide et amine disponibles de l'?-Tfm sérine a été effectuée, La réaction a conduit la formation respectivement du Nbenzylaminoalcool (R)-17 et (S)-17 avec un rendement de 58% et 57%

, Dans le but de transformer les aminoalcools mésylés 20 en aziridines correspondantes, nous avons suivi la méthode déjà utilisée dans première stratégie connaissant son efficacité et sa rapidité. En effet, en faisant réagir le dérivé mésylé 20 avec deux équivalents du benzylamine dans l'acétonitrile. Nous avons isolés les aziridine-2-carboxylates attendues au bout de 15 minutes

, Comme les deux groupes protecteurs des aziridines 21 synthétisées ne sont pas orthogonaux, nous avons élaboré une autre stratégie qui s'effectue selon la séquence activation-Streckersubstitution. Une réaction de type Strecker a été réalisée sur le dérivé activé 12 conduit aux ?-aminonitriles correspondantes

, L'hydrolyse de la fonction nitrile de l'aziridine génératrice d'une fonction acide, nécessite l'utilisation de l'hydroxyde de lithium dans un mélange THF/H2O. Après neutralisation, le composé (S)-26 a été obtenu avec un rendement de 88%

, Une application pertinente de cet aziridine carboxylique en tant qu'unité pseudopeptidique peut être utile en chimie des peptides. Plusieurs essais ont été réalisés dans le but de coupler l'aziridine carboxylique(S)-26 porteuse d'une chaîne phénylglycinol avec l'alanine

, Après optimisation des conditions opératoire, nous avons ainsi montré que le BoP-Cl est l'agent de couplage adéquat pour réussir cette amidification. Conclusion Générale et perspectives