Novel Approach to Selectively Functionalized Derivatives of Sucrose

Abstract

New synthetic routes to complex sucrose derivatives are presented. They are based on a highly selective silylation of the hydroxyl group at the C6′ position (‘fructose end’) in 2,3,3′,4,4′-penta-O-benzylsucrose followed by functionalization of the remaining (C-1′,6) positions. One of these synthons was used as a chiral platform for the construction of aza-macrocyclic systems.

Key words

sucrose - protecting groups - regioselectivity - phase-transfer catalysis - macrocycles

• References and Notes


Review:
• 1a Zhang XX, Bradshaw JS, Izatt RM. Chem. Rev. 1997; 97: 3313
• 1b Roca-Lopez D, Sadaba D, Delso I, Herrera RP, Tejero T, Merino P. Tetrahedron: Asymmetry 2010; 21: 2561
• 1c Shirakawa S, Maruoka K. Angew. Chem. Int. Ed. 2013; 52: 4312

See reviews:
• 2a Jarosz S, Listkowski A. Curr. Org. Chem. 2006; 10: 643
• 2b Bakó P, Keglevich G, Rapi Z, Tőke L. Curr. Org. Chem. 2012; 16: 297
• 3a Alonso-Lopez M, Bernabe M, Fernandez-Mayoralas A, Jimenez-Barbero M, Martin-Lomas M, Penades S. Carbohydr. Res. 1986; 150: 103
• 3b Alonso-Lopez MM, Martin-Lomas M, Penades S. Tetrahedron Lett. 1986; 27: 3551
• 3c Alonso-Lopez M, Barbat J, Fanton E, Fernandez-Mayoralas A, Gelas J, Horton D, Martin-Lomas M, Penades S. Tetrahedron 1987; 43: 1169
• 3d Alonso-Lopez M, Jimenez-Barbero M, Martin-Lomas M, Penades S. Tetrahedron 1988; 44: 1535
• 3e Dumont-Hornebeck B, Joly J.-P, Coulol J, Chapleur Y. Carbohydr. Res. 1999; 320: 147
• 4 Jarosz S, Listkowski A. J. Carbohydr. Chem. 2003; 22: 753
• 5 Brzuszkiewicz A, Ciunik Z, Jarosz S, Lewandowski B, Listkowski A. Tetrahedron 2005; 61: 8485
• 6 Jarosz S, Lewandowski B. Chem. Commun. 2008; 6399
• 7 Jarosz S, Lewandowski B. Carbohydr. Res. 2008; 343: 965
• 8 Potopnyk MA, Jarosz S. Eur. J. Org. Chem. 2013; 5117
• 9 Potopnyk MA, Lewandowski B, Jarosz S. Tetrahedron: Asymmetry 2012; 23: 1474
• 10 Jarosz S, Lewandowski B, Listkowski A. Synthesis 2008; 913
• 11 Lewandowski B, Jarosz S. Org. Lett. 2010; 12: 2532
• 12 Potopnyk MA, Cmoch P, Jarosz S. Org. Lett. 2012; 14: 4258
• 13 Mach M, Zawisza A, Lewandowski B, Jarosz S. Proven Carbohydrate Methods . Vol. I. Kovac P. Chap. 43 CRC Press, Taylor & Francis Group; Boca Raton, FL: 2011: 387-411 ; and references therein
• 14 See review: Queneau Y, Jarosz S, Lewandowski B, Fitremann J. Adv. Carbohydr. Chem. Biochem. 2007; 61: 217
• 15a Karl H, Lee CK, Khan R. Carbohydr. Res. 1982; 101: 31
• 15b Barros MT, Petrova K, Ramos AM. J. Org. Chem. 2004; 69: 7772
• 15c Barros MT, Correia-Da-Silva P, Petrova K, Potewar TM. Green Chem. 2011; 13: 1897
• 16 Gaweł A, Jarosz S. J. Carbohydr. Chem. 2010; 29: 332
• 17 Burdyńska J, Lewandowski B, Jarosz S. J. Carbohydr. Chem. 2011; 29: 403
• 18a Mitsunobu O. Synthesis 1981; 1
• 18b For the application of p-nitrobenzoic acid, see: Jarosz S, Głodek J, Zamojski A. Carbohydr. Res. 1987; 163: 289
• 19 Garegg PJ, Samuelsson B. J. Chem. Soc., Chem. Commun. 1979; 978
• 20 Mąkosza M, Fedoryński M. Curr. Catal. 2012; 1: 79
• 21 Alkylation of 12 with tert-Butyl bromoacetate: To a solution of diol 12 (1030 mg, 0.999 mmol) in toluene (15 mL), TBAB (32 mg, 0.099 mmol, 0.1 equiv) was added followed by 50% NaOH (10 mL). A solution of tert-butyl bromoacetate (0.16 mL, 1.1 mmol, 1.1 equiv) in toluene (0.84 mL) was added dropwise via syringe pump (for 1 h) and the mixture was vigorously stirred at r.t. for 165 min. H₂O (50 mL) was added, the phases were separated, and the aqueous one was extracted with Et₂O (2 × 50 mL). Combined organic solutions were washed with H₂O (25 mL) and brine (25 mL), dried, concentrated, and the oily residue was purified by flash chromatography (hexanes–EtOAc, 100:1 → 83:17) to yield the main product 16b (588 mg, 0.513 mmol, 51%), its regioisomer 16c (236 mg, 0.206 mmol, 21%), and diester 16a (298 mg, 0.236 mmol, 23%) as oils.
• 22 Synthesis of Macrocycle 21: To a solution of 20 (113 mg, 0.105 mmol) in MeCN (10 mL) anhyd Na₂CO₃ (330 mg, 3.1 mmol, 30 equiv) was added followed by anhyd KI (52 mg, 0.314 mmol, 3 equiv), and benzylamine (15 μL, 14.6 mg, 0.136 mmol, 1.3 equiv). The mixture was stirred at 80 °C in septum sealed flask for 48 h. Toluene (20 mL) was added and MeCN was removed under reduced pressure. The mixture was filtered through celite pad which was washed with EtOAc (40 mL), the filtrate was concentrated, and the residue was purified by flash chromatography (CH₂Cl₂–MeOH, 100:0 → 99:1) to afford a macrocycle 21 as an orange oil (100 mg, 0.101 mmol, 96%).