chapter  8
16 Pages

Glycal Transformation into 2-Deoxy Glycosides

In this chapter, we illustrate the synthesis of 2-deoxy glycosides via reaction of glycals with alcohols in the presence of triphenylphosphane hydrobromide (TPHB). A special emphasis is given to the reaction of glycals with long-chain alcohols, which leads to materials with a variety of potential applications, in particular as antimicrobial agents.1-3 The reaction is easy to perform and stereoselective, and when long-chain alcohols are used as synthons, the bioactivity of the formed 2-deoxy glycosides can be tuned by changing the glycal starting material structure, for example, 6-deoxygenation, and conguration.2 The acid-catalyzed addition of an alcohol to an acetylated glycal occurs usually with concomitant Ferrier allylic rearrangement, giving the 2,3-unsaturated derivative as major reaction product. However, when TPHB is used, as rst described by Bolitt et  al.4 to prepare 2-deoxy glycosides from glycals, formation of 2,3-unsaturated glycosides is minimal. Among the variety of glycals of d-and l-series already subjected to this procedure,1-3 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol (1) was selected to exemplify now the TPHB-mediated glycosylation of octanol and of dodecanol, which occurs with α-stereoselectivity, resulting from the anomeric effect. Glycosides 2-5 were obtained by reaction of glycal 1 in dichloromethane, using 2 equiv. alcohol at room temperature for 12 h. The 2-deoxy α-anomers were isolated in 69% yield (2) and 83% yield (4), and the

Experimental Methods ............................................................................................. 58 General Methods ................................................................................................. 58 General Procedure for the Glycosylation Reaction ............................................. 59 General Procedure for the Zemplén Deacetylation ............................................. 61

Octyl 2-deoxy-α-d-arabino-hexopyranoside (8) ............................................ 61 Octyl 2-deoxy-β-d-arabino-hexopyranoside (9) ............................................ 61 Dodecyl 2-deoxy-α-d-arabino-hexopyranoside (10) ..................................... 61 Dodecyl 2-deoxy-β-d-arabino-hexopyranoside (11) ..................................... 62

Acknowledgments .................................................................................................... 62 References ................................................................................................................ 72

2-deoxy β-glycosides were isolated in 15% (3) and 12% yield (5). The α-anomer of the octyl or dodecyl 2,3-unsaturated glycosides (6 and 7, respectively) was isolated in 2% yield, when the reaction was run at room temperature and in 6% (6) and 4% (7) when the reaction was run under reux. In order to simplify glycoside and nucleophile separation, the reaction was carried out with 1.05 equiv. alcohol at room temperature. Reaction time increased to 24 h, no Ferrier products were detected, and selectivity for the α-anomer was also improved as shown by the reaction yields obtained for compounds 2, 3, 4, and 5, isolated in 71%, 5%, 77%, and 7%, respectively. Zemplén deprotection of compounds 2-5 gave glycosides 8-11 in high yield (Scheme 8.1).