Development of a novel protecting group for natural product synthesis

Abstract

The use of 2,2- bis (4-nitrophenyl) ethanol (BnpeOH) has led to the development of a novel urethane-type protecting group, 2, 2- bis (4-nitrophenyl) ethoxycarbonyl (Bnpeoc). Studies have shown that this group is stable towards acids and tertiary amines whilst rapid and efficient cleavage can be effected by 1,5- diazabicyclo- [4.3.0] non-5 -ene (DBN) or 1,8-diazabicyclo[5.4.0]undec7-ene (DBU) with or without an equivalent of acetic acid. Nineteen amino acids have been protected using either the chloroformate (Bnpeoc -Cl) or the N- succinimidyl carbonate (Bnpeoc ONSu) of this group. These novel protected amino acids have been used to synthesise small peptides both in solution and solid phase. A highly efficient method for anchoring these protected amino acids to a 2- alkoxybenzylalcohol resin that avoids racemisation or dimer formation has also been developed.