Synthesis of cis-5-Trifluoromethylproline from l-Glutamic Acid

Stéphanie Ortial; Rajesh Dave; Zohra Benfodda; David Bénimélis; Patrick Meffre

doi:10.1055/s-0033-1340553

Synlett, Table of Contents

Synlett 2014; 25(4): 569-573
DOI: 10.1055/s-0033-1340553

letter

Synthesis of cis-5-Trifluoromethylproline from l-Glutamic Acid

Stéphanie Ortial

^aInstitut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Université de Montpellier I & II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

^bUNIVERSITE DE NIMES, Laboratoire de Chimie BioOrganique (LCBO), Place G. Péri, 30021 Nîmes Cedex 1, France Fax: +33(4)66364587 Email: patrick.meffre@unimes.fr

,

Rajesh Dave

,

Zohra Benfodda

^aInstitut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Université de Montpellier I & II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

^bUNIVERSITE DE NIMES, Laboratoire de Chimie BioOrganique (LCBO), Place G. Péri, 30021 Nîmes Cedex 1, France Fax: +33(4)66364587 Email: patrick.meffre@unimes.fr

,

David Bénimélis

^aInstitut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Université de Montpellier I & II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

^bUNIVERSITE DE NIMES, Laboratoire de Chimie BioOrganique (LCBO), Place G. Péri, 30021 Nîmes Cedex 1, France Fax: +33(4)66364587 Email: patrick.meffre@unimes.fr

,

Patrick Meffre*

^aInstitut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Université de Montpellier I & II, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

^bUNIVERSITE DE NIMES, Laboratoire de Chimie BioOrganique (LCBO), Place G. Péri, 30021 Nîmes Cedex 1, France Fax: +33(4)66364587 Email: patrick.meffre@unimes.fr

› Author Affiliations

Abstract

All articles of this category

Abstract

The diastereoselective synthesis of cis-5-trifluoromethylproline (5-Tfm-Pro) from l-glutamic acid is described. 5-Tfm-Pro could be obtained through a seven-step linear sequence. Trifluoromethylation of the glutamic-derived ester or aldehyde and subsequent reduction of the cyclic imine are the key steps in the synthesis.

Key words

amino acids - cis-5-trifluoromethylproline - fluorine - diastereoselective synthesis - imine - reduction

Full Text

References

References and Notes
1 Present address: Calyx Chemicals & Pharmaceuticals Ltd, A-37/38, MIDC, Dombivli East, Dist. Thane 421 203, Maharashtra, India.

2a Kowalczyk V, Prahl A, Derdowska I, Dawidowska O, Slaninovà J, Lammek B. J. Med. Chem. 2004; 47: 6020
2b Brackmann F, De Meijere A. Chem. Rev. 2007; 107: 4493
2c Fülöp F, Martinek TA, Toth GK. Chem. Soc. Rev. 2006; 35: 323

3a Yaron A, Naider F, Scharpe S. Crit. Rev. Biochem. Mol. Bio. 1993; 28: 31
3b Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpé S. FASEB J. 1995; 9: 736
3c Cai M, Cai C, Mayorov AV, Xiong C, Cabello CM, Soloshonok VA, Swift JR, Trivedi D, Hruby VJ. J. Peptide Res. 2004; 63: 116

4a Salwiczek M, Nyakatura EK, Gerling UI. M, Ye S, Koksch B. Chem. Soc. Rev. 2012; 41: 2135 ; and references therein
4b Qiu X.-L, Qing F.-L. Eur. J. Org. Chem. 2011; 3261 ; and references therein
4c Yoder NC, Kumar K. Chem. Soc. Rev. 2002; 31: 335
4d Aceña JL, Sorochinsky AE, Soloshonok VA. Synthesis 2012; 44: 1591
4e Aceña JL, Sorochinsky AE, Moriwaki H, Sato T, Soloshonok VA. J. Fluorine Chem. 2013; 155: 21
4f Sorochinsky AE, Soloshonok VA. J. Fluorine Chem. 2010; 131: 127

5a Soloshonok VA. Fluorine-Containing Synthons. Oxford University Press, 2005
5b Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology . Blackwell Publishing, Ltd; Chichester: 2009
5c Mikami K, Fustero S, Sanchez-Rosello M, Aceña JL, Soloshonok V, Sorochinsky A. Synthesis 2011; 3045

6 Chaume G, Van Severen M.-C, Marinkovic S, Brigaud T. Org. Lett. 2006; 8: 6123
7 Caupène C, Chaume G, Ricard L, Brigaud T. Org. Lett. 2009; 11: 209
8 Chaume G, Lensen N, Caupène C, Brigaud T. Eur. J. Org. Chem. 2009; 5717
9 Jlalia I, Lensen N, Chaume G, Dzhambazova E, Astasidi L, Hadjiolova R, Bocheva A, Brigaud T. Eur. J. Med. Chem. 2013; 62: 122
10 Gulevich AV, Shevchenko NE, Balenkova ES, Röschenthaler G.-V, Nenajdenko VG. Synlett 2009; 403
11 Li Q, Ding C.-H, Li X.-H, Weissensteiner W, Hou X.-L. Synthesis 2012; 44: 265
12 Li G.-H, Tong M.-C, Li J, Tao H.-Y, Wang C.-J. Chem. Commun. 2011; 47: 11110
13 Li Q.-H, Xue Z.-Y, Tao H.-Y, Wang C.-J. Tetrahedron Lett. 2012; 53: 3650
14 Qiu X.-L, Qing F.-L. J. Chem. Soc., Perkin Trans. 1 2002; 2052
15 Qiu X.-L, Qing F.-L. J. Org. Chem. 2002; 67: 7162
16 Del Valle JR, Goodman M. Angew. Chem. Int. Ed. 2002; 41: 1600
17 Chaume G, Barbeau O, Lesot P, Brigaud T. J. Org. Chem. 2010; 75: 4135

18a Chaume G, Feytens D, Chassaing G, Lavielle S, Brigaud T, Miclet E. New J. Chem. 2013; 37: 1336
18b Chaume G, Simon J, Caupène C, Lensen N, Miclet E, Brigaud T. J. Org. Chem. 2013; 78: 10144

19 Khangarot RK, Kaliappan KP. Eur. J. Org. Chem. 2013; 13: 2692
20 Kondratov IS, Dolovanyuk VG, Tolmachova NA, Gerus II, Bergander K, Fröhlich R, Haufe G. Org. Biomol. Chem. 2012; 10: 8778
21 Padrón JM, Kokotos G, Martín T, Markidis T, Gibbons WA, Martín VS. Tetrahedron: Asymmetry 1998; 9: 3381
22 Wiedemann J, Heiner T, Mloston G, Prakash GK. S, Olah GA. Angew. Chem. Int. Ed. 1998; 37: 820
23 The level of drying of all reagents and solvents required for this reaction might be the cause of the capricious nature of this transformation as discussed by the authors (Note: commercially available 1 M solution of TBAF in THF usually contains 5% of H₂O).
24 Adamczyk M, Johnson DD, Reddy RE. Tetrahedron: Asymmetry 1999; 10: 775
25 Ilies M, Dowling DP, Lombardi PM, Christianson DW. Bioorg. Med. Chem. Lett. 2011; 21: 5854
26 Bodanszky M, Bodanszky A In The Practice of Peptide Synthesis . Springer Verlag; Berlin: 1984: 177
27 Experimental Procedure for 6: Using 4 M HCl–1 M NaOH: Compound 5 (1.2 mmol, 1 equiv) was dissolved in THF (10 mL) and a THF–12 M HCl mixture (11 mL/9 mL) was added dropwise and the solution was stirred at r.t. for 30 min. After concentration in vacuo, MeOH (2.4 mL) and 1 M NaOH (3.36 mL) were added to the crude product. The solution was stirred at r.t. for 2 h and concentrated in vacuo. Purification over Dowex 50WX8, eluting with H₂O then 5% aq NH₃ followed by purification over RP 18 silica gel, eluting with H₂O afforded the imine 6 as an off-white solid after complete removal of the H₂O (0.15 g, 0.83 mmol, 69%). Using 6 M HCl: Compound 5 (0.84 mmol, 1 equiv) was dissolved in 6 M HCl (3.5 mL). The solution was heated at 60 °C until reaction was complete (24 h) and the brown mixture then washed with Et₂O (2 ×) and concentrated in vacuo. Purification following the procedure previously described afforded 6 in 59% yield (0.09 g, 0.50 mmol). ¹H NMR (300 MHz, DMSO-d ₆): δ = 4.62 (m, 1 H), 2.76 (m, 2 H), 2.13 (m, 2 H). ¹³C NMR (75.45 MHz, DMSO-d ₆): δ = 173.3 (C), 164.3 (q, J _CCF = 34.8 Hz, C), 120.5 (q, J _CF = 273 Hz, C), 77.9 (CH), 33.5, 27.0 (CH₂). ¹⁹F NMR (282.4 MHz, DMSO-d ₆): δ = −68.8 (d, J _HF = 2.8 Hz). [α]_D ²⁰ 6.1 (c = 1.0, DMSO). HRMS (ESI−): m/z [M − H]⁻ calcd for C₆H₅NO₂F₃: 180.0272; found: 180.0273.

28a Yasumoto M, Ueki H, Soloshonok VA. J. Fluorine Chem. 2007; 128: 736
28b Soloshonok VA, Yasumoto M. J. Fluorine Chem. 2006; 127: 889
28c Ono T, Kukhar VP, Soloshonok VA. J. Org. Chem. 1996; 61: 6563

29 Experimental Procedure for 7: The cyclic imine 6 (0.27 mmol, 1 equiv) was dissolved in anhyd DMF (2 mL) and Pd/C was (10−15 wt%) added. The solution was degassed at −78 °C for 5 min and the flask was filled with H₂. After 16 h at r.t., the reaction was complete. The solution was filtered over a pad of Celite^® and concentrated under high vacuum. Purification over RP 18 silica gel eluting with H₂O containing a few drops of 12 M HCl afforded 5-Tfm-Pro as its hydrochloride salt (0.061 g, 0.27 mmol, 100%). ¹H NMR (300 MHz, D₂O): δ = 4.41 (m, 2 H), 2.05−2.42 (m, 4 H). ¹³C NMR (75.45 MHz, D₂O): δ = 171.2 (C), 123.0 (q, J _CF = 278 Hz, C), 61.5 (CH), 59.5 (q, J _CCF = 33.7 Hz, C), 27.1, 23.7 (CH₂). ¹⁹F NMR (282.4 MHz, D₂O): δ = −72.3 (d, J _HF = 7.06 Hz, cis isomer), −73.0 (d, J _HF = 7.34 Hz, trans isomer). MS (ESI−): m/z = 181.94 ([M − H]⁻). HRMS (ESI−): m/z [M − H]⁻ calcd for C₆H₇NO₂F₃: 182.0429; found: 182.0430.

30a Brun M.-P, Martin A.-S, Garbay C, Bischoff L. Tetrahedron Lett. 2003; 44: 7011
30b Mota AJ, Langlois N. Tetrahedron Lett. 2003; 44: 1141
30c Beausoleil E, L’Archevêque B, Bélec L, Atfani M, Lubell WD. J. Org. Chem. 1996; 61: 9447

31 Abdel-Magid AF, Carson KG, Harris BD, Maryanoff CA, Shah RD. J. Org. Chem. 1996; 61: 3849

32a Connon SJ. Angew. Chem. Int. Ed. 2006; 45: 3909
32b Guo Q.-S, Du D.-M, Xu J. Angew. Chem. Int. Ed. 2008; 47: 759
32c Rueping M, Tato F, Schoepke FR. Chem. Eur. J. 2010; 16: 2688

Supplementary Material

Supporting Information