Synthesis of Methyl Axenoside and Methyl 3-epi-Axenoside via Ate-Mediated Allylic Substitution (AMAS)

Abstract

An ate-mediated allylic substitution (AMAS) of vinylboronates is utilized in the divergent syntheses of the sugars methyl axenoside and methyl 3-epi-axenoside. Other key steps of the synthesis involve the dihydroxylation of the resulting allylic alcohol and selective oxidation of the resultant diol. Benefits of this methodology are also discussed.

Key words

asymmetric synthesis - boron - homogeneous catalysis - natural products - total synthesis

• References and Notes


Axenomycin:
• 1a Arcamone F, Barbieri W, Franceschi G, Penco S, Vigevani A. J. Am. Chem. Soc. 1973; 95: 2008

Polyketomycin:
• 1b Momose I, Chen W, Kinoshita N, Iinuma H, Hamada M, Takeuchi T. J. Antibiot. 1998; 51: 21
• 1c Momose I, Chen W, Kinoshita N, Iinuma H, Hamada M, Takeuchi T. J. Antibiot. 1998; 51: 26
• 1d Micalizzi DS, Dougherty JP, Noecker LA, Smith GR, Giuliano RM. Tetrahedron: Asymmetry 2003; 14: 3183

Dutomycin:
• 1e Xuan L.-J, Xu S.-H, Zhang H.-L, Xu Y.-M. J. Antibiot. 1992; 45: 1974
• 2 Garegg PJ, Norberg T. Acta Chem. Scand. B 1975; 29: 507
• 3 Smith GR, Villani FJ. Jr, Failli L, Giuliano RM. Tetrahedron: Asymmetry 2000; 11: 139

For other de novo syntheses of deoxy sugars, see:
• 4a Ahmed MdM, Berry BP, Hunter TJ, Tomcik DJ, O’Doherty GA. Org. Lett. 2005; 7: 745
• 4b Ahmed MdM, O’Doherty GA. Tetrahedron Lett. 2005; 46: 3015
• 4c Ahmed MdM, O’Doherty GA. Carbohydrate Res. 2006; 341: 1505
• 5 Smaltz DJ, Švenda J, Myers AG. Org. Lett. 2012; 14: 1812
• 6 Park JK, Ondrusek BA. McQuade D. T. Org. Lett. 2012; 14: 4790
• 7 Ondrusek BA, Park JK, McQuade DT. Synlett 2014; 25: 239
• 8 See Supporting Information for a discussion on unsuccessful methodologies. All compounds not found in the article will be numbered sequentially beginning with 17.
• 9 Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483

For references on the dihydroxylation of alkenes bearing allylic heteroatoms, see:
• 10a Donohoe TJ, Moore PR, Waring MJ. Tetrahedron Lett. 1997; 38: 5027
• 10b Kallatsa OA, Koskinen AM. P. Tetrahedron Lett. 1997; 38: 8895
• 10c Donohoe TJ, Blades K, Helliwell M, Moore PR, Winter JJ. G. J. Org. Chem. 1999; 64: 2980
• 10d Blades K, Donohoe TJ, Winter JJ. G, Stemp G. Tetrahedron Lett. 2000; 41: 4701
• 10e Donohoe TJ, Blades K, Moore PR, Waring MJ, Winter JJ. G, Helliwell M, Newcombe NJ, Stemp G. J. Org. Chem. 2002; 67: 7946
• 11 See Supporting Information for additional procedural information.
• 12 Sharif EU, Wang H.-YL, Akhmedov NG, O’Doherty GA. Org. Lett. 2014; 16: 492
• 13 See Supporting Information for a discussion on unsuccessful strategies toward acetonide deprotection–cyclization.
• 14 Kobayashi S, Reddy RS, Sugiura Y, Sasaki D, Miyagawa N, Hirama M. J. Am. Chem. Soc. 2001; 123: 2887
• 15 The Myers group⁴ suggests that these α/β ratios are a thermodynamic mixture.