Synthesis towards new C-glycoside derivatives ofmultivalent carbohydrates

  • Faisal Jamshaid

Student thesis: Master of Philosophy


C-Allyl mannopyranosides, 3-(2,3,4,6-tetra-O-acetyl-alpha,β-D-mannopyranosyl) propene and 3-(2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl) propene, were successfully synthesised fromalpha-D-methyl mannopyranoside. In this manner, C-allyl mannopyranosides were obtained in39-60% yields, with alpha:β 4:1 anomeric selectivity for 3-(2,3,4,6-tetra-O-acetyl-alpha,β-Dmannopyranosyl)propene, while 3-(2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl) propenewas produced exclusively as the alpha-anomer.Sulfur-linked carbohydrates were successfully synthesised [in the presence of 1,1'-azobis(cyclohexanecarbonitrile) as radical initiator] via the thiol-ene click reaction. Each reaction afforded the corresponding sulfide spacer-arm glycosides in good yields. An efficient two-step methodology has been developed for the synthesis of the novel primary thiol group-containing sugars, (2R,3S,4R,5R,6R)-2-(acetoxymethyl)-6-(3- mercaptopropyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate and 3-((2R,3R,4R,5S,6R)-3,4,5- tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)propane-1-thiol. In this way, free thiol group-containing sugars were obtained in 73% and 60% yields respectively, with an anomeric ratio of alpha:β 2.5:1 for (2R,3S,4R,5R,6R)-2-(acetoxymethyl)-6-(3- mercaptopropyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate and 3-((2R,3R,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)propane-1-thiol being obtained as the alpha-anomer only. The thiol-ene click reaction was thus shown to be a viable method to obtain novel free thiolcontainingC-glycosides. These compounds are suitable for future applications towards asmultivalent saccharides via the use of the primary thiol function for click thiol-eneconjugations, or other S-based conjugation chemistry.
Date of Award31 Dec 2013
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorJohn Gardiner (Supervisor)

Cite this