Synthesis of Septanosides through an Oxyglycal Route N. Vijaya Ganesh and N. Jayaraman* Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India jayaraman@orgchem.iisc.ernet.in ReceiVed March 4, 2007 A new route to synthesize septanoside derivatives from protected 2-hydroxyglycals is reported. Ring expansion of a pyranoside to a septanoside was achieved through key reactions of a cyclopropanation, ring opening, oxidation, and reduction. Methyl septanoside derivatives, namely, methyl R-D-glycero-D- talo-septanoside and methyl R-D-glycero-L-altro-septanoside, were synthesized in an overall yield of 35% and 46%, respectively, from the corresponding protected 2-hydroxy glycals. Introduction The seven-membered cyclic sugar derivatives, namely, sep- tanoses and septanosides, are less commonly known sugar homologues. 1 Studies of the acid-catalyzed formation of ac- etonides from unsubstituted free sugars, by Stevens and co- workers, have demonstrated the first instance of a preparative method to isolate the septanoside derivatives. 2 Synthesis of cyclic seven-membered sugars, namely, septanoses, arise inter- est, partly due to the desire to identify the configurational and conformational features of septanoses, and the attendant pos- sibilities to explore their chemical and biological properties. 3 A few methods of septanoside formation are the following: (i) hemiacetal or acetal formation from a linear precursor containing aldehyde and appropriately positioned hydroxyl group; 2,4,5 (ii) pyridinium chloride mediated ring-opening of a protected glucopyranoside; 6 (iii) condensation of dialdehydes with active methylene compounds; 7 (iv) ring-closing metathesis reactions of appropriately installed diene derivatives; 8 (v) expansion of a glycal via cyclopropanation and ring opening; 9 and (vi) Baeyer- Villiger oxidation of inositol derivatives. 10 We desired that 2-hydroxyglycals would form as suitable substrates for ring expansion, leading to the formation of septanoside derivatives, retained with hydroxyl groups in each carbon of the septanoside. With this intention, we have explored a ring expansion reaction, wherein a cyclic six-membered sugar derivative is converted directly to a cyclic seven-membered sugar derivative, through a methylene insertion, oxidation, and reduction reactions on oxyglycal precursors. Syntheses of septanosides, starting from oxyglycal derivatives of gluco-and galactopyranosides, are presented herein. Results and Discussion (a) Synthesis of Methyl R-D-glycero-D-talo-Septanoside. The synthesis was initiated from methyl 2,3,4,6-tetra-O-benzyl- R-D-glucopyranoside (1). The O-benzyl-protected oxyglycal 4 was synthesized analogous to a procedure reported for the corresponding O-acetyl- and O-benzoyl-protected oxyglycals. 11 Acetolysis of the benzyl derivative 1, followed by treatment with HBr/AcOH, led to the formation of bromide 2 (Scheme (1) Collins, P. M.; Ferrier, R. J. Monosaccharides: Their Chemistry and Their Roles in Natural Products; John Wiley & Sons: Chichester, UK, 1998; pp 40-42. (2) Stevens, J. D. Carbohydr. Res. 1972, 21, 490-492. (3) For review on seven-membered-ring sugars, see: (a) Pakulski, Z. Pol. J. Chem. 1996, 70, 667-707. (b) Pakulski, Z. Pol. J. Chem. 2006, 80, 1293-1326. (4) Micheel, F.; Suckfu¨ll, F. Ann. Chem. 1933, 502, 85. (5) Johnson, C. R.; Golebiowski, A.; Steensma, D. H. J. Am. Chem. Soc. 1992, 114, 9414-9418. (6) Contour, M. O.; Fayet, C.; Gelas, J. Carbohydr. Res. 1990, 201, 150- 152. (7) (a) Baschang, G. Ann. Chem. 1963, 663, 167. (b) Wolfrom, M. L.; Nayak, U. G.; Radford, T. Proc. Natl. Acad. Sci. U.S.A. 1967, 58, 1848. (c) Butcher, M. E.; Ireson, J. C.; Lee, J. B.; Tyler, M. J. Tetrahedron 1977, 33, 1501-1507. (8) (a) Ovaa, H.; Leeuwenburgh, M. A.; Overkleeft, H. S.; van der Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1998, 39, 3025-3028. (b) Peczuh, M. W.; Snyder, N. L. Tetrahedron Lett. 2003, 44, 4057-4061. (c) DeMatteo, M. P.; Snyder, N. L.; Morton, M.; Hadad, C. M.; Peczuh, M. W. J. Org. Chem. 2005, 70, 24-38. (d) Castro, S.; Fyvie, S.; Hatcher, S. A.; Peczuh, M. W. Org. Lett. 2005, 21, 4709-4712. (e) DeMatteo, M. P.; Mei, S.; Fenton, R.; Morton, M.; Hadad, C. M.; Peczuh, M. W. Carbohydr. Res. 2006, 341, 2927-2945. (9) (a) Ramana, C. V.; Murali, R.; Nagarajan, M. J. Org. Chem. 1997, 62, 7694-7703. (b) Hoberg, J. O. J. Org. Chem. 1997, 62, 6615-6618. (c) Cousins, G. S.; Hoberg, J. O. Chem. Soc. ReV. 2000, 29, 165-174. (d) Batchelor, R.; Hoberg, J. O. Tetrahedron Lett. 2003, 44, 9043-9045. (10) (a) Chida, N.; Tobe, T.; Ogawa, S. Tetrahedron Lett. 1994, 35, 7249-7252. (b) Fukami, H.; Koh, H.-S.; Sakata, T.; Nakajima, M. Tetrahedron Lett. 1968, 1701-1704. 5500 J. Org. Chem. 2007, 72, 5500-5504 10.1021/jo070444e CCC: $37.00 © 2007 American Chemical Society Published on Web 06/22/2007