Enantioselective Synthesis of Dihydrofuranylglycine, Furanylglycine, ­Furanylalanine and homo-Furanylalanine Derivatives

Abstract

Enantiomerically pure nor-furanomycin, furanylglycine, furanylalanine and homo-furanylalanine derivatives were prepared from appropriate amino acid derived dienes using ring-closing ­metathesis as the key step.

Key-words

α-amino acids - ring-closing metathesis - aromatization - enantioselective

References

• 1a Williams RM. Synthesis of Optically Active α-Amino Acids   Vol. 7:  Baldwin JE. Magnus PD. Organic Chemistry Series, Pergamon Press; Oxford: 1989. 
• 1b Barrett GC. Amino Acids, Peptides and Proteins   Vol. 32:  The Chemical Society; London: 2001. 
• 2a Cativiela C. Diaz-de-Villegas MD. Tetrahedron: Asymmetry  1998,  9:  3517 
• 2b Rutjes FPJT. Wolf LB. Schoemaker HE. J. Chem. Soc., Perkin Trans. 1  2000,  4197 
• 2c Desrosiers J.-N. Cote A. Charette AB. Tetrahedron  2005,  61:  6186 ; and references cited therein
• 3 Coppola GM. Schuster HF. Asymmetric Synthesis: Construction of Chiral Molecules Using Amino Acids   Wiley-Interscience; New York: 1989. 
• 4a Jackson RFW. Wishart N. Wood A. James K. Wythes MJ. J. Org. Chem.  1992,  57:  3397 
• 4b Collier PN. Patel I. Taylor RJK. Tetrahedron Lett.  2002,  43:  3401 
• 4c Harwood LM. Manage AC. Robin S. Hoes SFG. Watkin DJ. Williams CE. Synlett  1993,  777 
• 4d Crisp GT. Meyer AG. J. Org. Chem.  1992,  57:  6972 
• 4e α-Amino Acid Synthesis, O’Donnell, M. J., Ed. Tetrahedron Symposium-in-Print, Number 33  1988,  44:  5253-5605  
• 5 Garner P. Park JM. Org. Synth.  1992,  70:  18 
• 6 McKillop A. Taylor RJK. Watson R. Lewis N. Synthesis  1994,  31 
• 7a Strekowski L. Wydra RL. Cegla MT. Czarny A. Harden DB. Patterson SE. Battiste MA. Coxon JM. J. Org. Chem.  1990,  55:  4777 
• 7b Strekowski L. Cegla MT. Harden DB. Mokrosz JL. Mokrosz MJ. Tetrahedron Lett.  1988,  29:  4265 
• 8 Meffre P. Vo-Quang L. Vo-Quang Y. Le Goffic F. Amino Acid Derivatives: A Practical Approach   Barrett GC. Oxford Univ. Press; Oxford: 1999.  p.115-131  
• 9a Katagiri K. Tori K. Kimura Y. Yoshida T. Nagasaki T. Minato H. J. Med. Chem.  1967,  10:  1149 
• Recent reports on the synthesis of furanomycin:
• 9b VanBrunt MP. Standaert RF. Org Lett.  2000,  2:  705 
• 9c Zhang JH. Clive DLJ. J. Org. Chem.  1999,  64:  1757 
• 9d Kang SH. Lee SB. Chem. Commun.  1998,  761 
• 10 Franciotti M. Mann A. Taddei M. Tetrahedron Lett.  1991,  32:  6783 
• 11 Shimizu M. Wakioka I. Fujisawa T. Tetrahedron Lett.  1997,  38:  6027 
• 12 For a recent review, see: Grubbs RH. Tetrahedron  2004,  60:  7117 
• 13 Brown HC. Garg CP. Liu K.-T. J. Org. Chem.  1971,  36:  387 
• 14a For a review on arylglycines, see: Williams RM. Hendrix JA. Chem. Rev.  1992,  92:  889 
• Recent reports on heterocyclic amino acids:
• 14b Cabbarocas E. Rafel S. Ventura M. Villalgordo JM. Synlett  2000,  595 
• 14c Jones SW. Palmer CF. Paul JM. Tiffin PD. Tetrahedron Lett.  1999,  40:  1211 
• 14d Capek P. Pohl R. Hocek M. J. Org. Chem.  2004,  69:  7985 
• 15 Drueckhammer DG. Barbas CF. Nozaki K. Wang C.-H. J. Org. Chem.  1988,  53:  1607 
• 16a Chattopadhyay SK. Pal BK. Maity S. Chem. Lett.  2003,  32:  1190 ; confer ref. 16b
• 16b Kotha S. Mandal K. Tetrahedron Lett.  2004,  45:  2585 
• 17 Shimamoto K. Ishida M. Shinozaki H. Ohfune Y. J. Org. Chem.  1991,  56:  4167 

18

All new compounds reported gave satisfactory spectroscopic data.
Experimental Procedure for the One-Pot RCM and DDQ Oxidation.
Grubbs’ catalyst 6 (5 mol%) was added under argon atmosphere to a solution of 18 (62 mg, 0.2 mmol) in dry degassed CH₂Cl₂ (10 mL) and the resulting mixture was stirred at r.t. for 4 h. A solution of DDQ (91 mg, 0.4 mmol) in benzene (16 mL) was then added and the resulting mixture was heated to reflux for 16 h. Evaporation of the solvent in vacuo followed by chromatography of the residual mass on silica gel using 5% EtOAc-petroleum ether afforded 19 as a viscous liquid (30 mg, 54%). [α]_D +6.5 (c 0.75, CH₂Cl₂). IR (neat): 2979, 1699, 1390, 1366 cm^-1. ¹H NMR (400 MHz, CDCl₃, mixture of rotamers): δ = 7.31 (1 H, s), 6.27 (1 H, s), 6.04 (1 H, d, J = 4.1 Hz), 4.14 (1 H, d, J = 5.8 Hz), 4.03 (1 H, d, J = 4.2 Hz), 3.88-3.86 (2 H, m), 3.12 (1 H, d, J = 14.3 Hz), 3.01 (1 H, d, J = 14.3 Hz), 2.85-2.77 (2 H, m), 1.48 (s, 9 H), 1.24 (6 H, merged s). MS (TOF MS ES+): m/z = 304 [M⁺ + Na]. Anal. Calcd for C₁₅H₂₃NO₄ (%): C, 64.0; H, 8.2; N, 5.0. Found: C, 64.3; H, 8.4; N, 4.8.