Direct Synthesis of Glycidic Bicyclic Scaffolds in Water without Protecting Groups

Abstract

Bicyclic scaffolds obtained from C-allyl glycosides have been synthesized in water, without the use of protecting groups. The scaffolds have been functionalized with different groups for chemoselective ligation.

Key words

bicyclic scaffold - darbohydrate - green chemistry - unprotected

References

• 1 Cipolla L. Peri F. La Ferla B. Redaelli C. Nicotra F. Curr. Org. Synth.  2005,  2:  153 ; and references cited therein
• 2a Papagerorgiou C. Haltiner R. Bruns C. Petcher TJ. Bioorg. Med. Chem. Lett.  1992,  2:  135 
• 2b Hirshmann R. Nicolaou PS. Leahy EM. Salvino J. Arison B. Cichy MA. Spoors PG. Shakespear WC. Sprengeler PA. Hamley P. Smith AB. Reisine T. Raynor K. Maechler L. Donaldson C. Vale W. Freidinger FM. Cascieri MR. Strader CD. J. Am. Chem. Soc.  1993,  115:  12550 
• 2c Nicolaou KC. Trujillo JI. Chibale K. Tetrahedron  1997,  53:  8751 
• 2d Le Diguaher T. Boudon A. Elwell C. Peterson DE. Billington DC. Bioorg. Med. Chem. Lett.  1996,  6:  1983 
• 2e Dinh TQ. Smith CD. Du X. Armstrong RW. J. Med. Chem.  1998,  41:  981 
• 2f Boer J. Gottschling D. Schuster A. Semmrich M. Holzmann B. Kessler H. J. Med. Chem.  2001,  44:  2586 
• 2g Boer J. Gottschling D. Schuster A. Holzmann B. Kessler H. Angew. Chem. Int. Ed.  2001,  40:  3870 
• 2h Murphy PV. O’Brie JL. Gorey-Feret LJ. Smith AB. Tetrahedron  2003,  59:  2259 
• 3a Fuchs EF. Lehmann J. Chem. Ber.  1975,  108:  2254 
• 3b Fuchs EF. Lehmann J. J. Carbohydr. Res.  1975,  45:  135 
• 3c Nicolaou KC. Florke HM. Egan G. Barth T. Estevez VA. Tetrahedron Lett.  1995,  36:  1775 
• 3d Smith MD. Long DD. Marquess DG. Claridge TDW. Fleet GWJ. Chem. Commun.  1998,  2039 
• 3e Locardi E. Stoeckle M. Gruner S. Kessler H. J. Am. Chem. Soc.  2001,  123:  8189 
• 4a Peri F. Cipolla L. La Ferla B. Nicotra F. Chem. Commun.  2000,  2303 
• 4b Forni E. Cipolla L. Caneva E. La Ferla B. Peri F. Nicotra F. Tetrahedron Lett.  2002,  43:  1355 
• 4c Polyak F. Lubell WD. J. Org. Chem.  2001,  66:  1171 
• 4d Cipolla L. Forni E. Jiménez-Barbero J. Nicotra F. Chem.-Eur. J.  2002,  8:  3976 
• 5a Bennek JA. Gray GA. J. Org. Chem.  1987,  52:  892 
• 5b Broxterman HJG. Kooreman PA. van den Elst H. Roelen HCPF. van der Marel GA. van Boom JH. Recl. Trav. Chim. Pays-Bas  1990,  109:  583 
• 6a MacMillan D. Bill RM. Sage KA. Fern D. Flitsch SL. Chem. Biol.  2001,  8:  133 
• 6b MacMillan D. Dains AM. Bayrhuber M. Flitsch SL. Org. Lett.  2002,  4:  1467 
• 7a Zhu X. Pachamuthu K. Schmidt RR. J. Org. Chem.  2003,  68:  5641 
• 7b Lubineau A. Malleron A. Le Narvor C. Tetrahedron Lett.  2000,  41:  8887 
• 7c Peri F. Cipolla L. La Ferla B. Nicotra F. C. R. Chim.  2003,  6:  635 ; and references cited therein
• 7d Kolb HC. Sharpless KB. Drug Discov. Today  2003,  8:  1128 ; and references cited therein

8

General Procedure.
Primary alcohol (0.11 mmol) was dissolved in a sat. solution of NaHCO₃ (1.5 mL), and then KBr (0.1 equiv) and TEMPO (0.06 equiv) were added. The temperature was lowered to 15-18 °C and an aq solution of NaOCl (5%; 1 mL) was slowly added. The reaction was stirred at r.t. for 2 h then concentrated under reduced pressure. The products were purified by flash chromatography (EtOAc-MeOH-H₂O, 6:4:0.5).

9

Compound 9 (0.15 mmol) and Cs₂CO₃ (0.15 mmol) were dissolved in dry MeOH (1 mL). After 0.5 h the solution was added to a solution of compound 4a in dry MeOH-DMF 1:1 (2 mL) and left stirring at r.t. for 12 h. The reaction mixture was then concentrated under reduced pressure and the product was purified by flash chromatography (EtOAc-MeOH, 9:1).