An improved preparation of a tertiary alcohol proline linker and its use in a synthesis of mosquito oostatic hormone
An improved synthesis of 4-(3'-hydroxy-3'-methylbutyl)phenoxyacetic acid was developed using THF to overcome solubility problems initially encountered in trying to reproduce the published preparation. This hydroxyacid linker was coupled to aminomethyl polystyrene resin and used for a synthesis of the mosquito oostatic hormone by the Fmoc protocol. Attempts to prepare this insect peptide by other techniques had failed because of loss of cyclo-Pro2 from the resin.
Fmoc-based Solid-phase Peptide Synthesis using a New t-Alcohol Type 4-(1',1'-Dimethyl-1'-hydroxypropyl)phenoxyacetyl Handle (DHPP)-Resin (Fmoc = fluoren-9-ylmethoxycarbonyl)
The loss of C-terminal dipeptide through diketopiperazine formation during Fmoc-based solid-phase peptide synthesis has been effectively suppressed by anchoring the first Fmoc amino acid chloride to a new 4-(1',1'-dimethyl-1'-hydroxypropyl)phenoxyacetyl handle (DHPP)-resin; this new t-alcohol type DHPP-resin has been successfully applied to the solid-phase synthesis of bradykinin potentiator B (an eleven-residue peptide) (Fmoc = fluoren-9-ylmethoxycarbonyl).