Ingrid 't Hart

55 Synthesis of globo-series glycolipids 3 Chapter 3 Chemical and chemoenzyma�c synthesis of globo-series glycosphingolipids Abstract : Globo-series glycosphingolipids (GSLs) are stem cell biomarkers and play key roles in various diseases such as cancer and bacterial and viral infec�ons. Recent reports indicate that the ceramidemoiety of GSLs can modulate protein binding, which encouraged us to synthesize globo-series GSLs. Full chemical synthesis provided globally protected globopentaosylsphingosine (Gb5-Sph). However, Birch reduc�on to cleave the benzyl ethers was unsuccessful, possibly due to solubility issues. A chemoenzyma�c approach was then pursued, in which Gb3-Sph was chemically synthesized and extended by the bifunc�onal bacterial enzyme LgtD from Haemophilus inlfuenzae. LgtD completely converted free reducing Gb3 and Gb4 to Gb4 and Gb5, respec�vely. Although par�al conversion of the Gb3- and Gb4-glycolipids was observed, Gb4-Sph and Gb5-Sph could be obtained. Coupling of Gb3-Sph, Gb4-Sph and Gb5-Sph with palmi�c acid provided Gb3-Cer, Gb4-Cer and Gb5-Cer.