Solid phase-mediated cyclization of head-to-tail peptides Problems associated with side chain anchoring
Valero, M.L.; Giralt, E.; Andreu, D.
Tetrahedron Letters 37(24): 4229-4232
ISSN/ISBN: 0040-4039 DOI: 10.1016/0040-4039(96)00803-9
Solid-phase synthesis of cyclic head-to-tail peptides using Boc-based protection schemes and side chain anchoring via the -carboxyl of Asp can lead to substantial levels of epimerization at the -carbon of Asp. These problems arise largely from the chemistry used for the incorporation of Boc-Asp(OH)-OFm to the polymer. Several conditions for the attachment of this -carboxyl to hydroxymethyl or bromomethyl resins have been evaluated, in an attempt to achieve effective, epimerization-free anchorings. The most successful routes involve the use of cesium or zinc salts of Boc-Asp(OH)-OFm.