Temporary Carbohydrate Diol Protection with Ester Groups : Orthogonality under Solid-Phase Oligosaccharide Synthesis ConditionsConditions

Abstract

For regioselective deprotection studies under SPOS conditions the glucosamine derivatives 4ab/4ba, 4ac/4ca and 4ad/4da – with Fmoc/PA, Fmoc/Lev or Fmoc/Alloc, respectively, as temporary ester protecting groups at 3-O and 4-O – were prepared. Fmoc cleavage with triethylamine in 4ab or 4ba led to PA migration, so the Fmoc/PA pair does not permit regioselective access to the vicinal hydroxy groups. Under the same reaction conditions no Lev migration in 4ac/4ca or Alloc migration in 4ad/4da was observed. Lev removal with hydrazinium acetate in 4ac/4ca and Alloc removal with Pd0 and dimedone as nucleophile in 4ad/4da was also not accompanied by Fmoc migration, so the Fmoc/Lev pair and the Fmoc/Alloc pair can be successfully employed for regioselective access to the 3-hydroxy or the 4-hydroxy group, respectively. However, Fmoc cleavage with piperidine in 4ac/4ca led to Lev migration, and the use of a basic nucleophile for Alloc cleavage also led to Fmoc migration in 4ad. 4-O-Fmoc protection was also combined with Nap ether protection in 4ea. These two groups could be readily and regioselectively removed, thus providing another useful pair for temporary protection of vicinal diols.