Temporary Carbohydrate Diol Protection with Ester Groups – Orthogonality under Solid‐Phase Oligosaccharide Synthesis Conditions

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 Pd 0 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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)