Solution-phase parallel synthesis with oligoethylene glycol sorting tags. Preparation of all four stereoisomers of the hydroxybutenolide fragment of murisolin and related acetogenins

The principles of the oligoethylene glycol (OEG) mixture synthesis are illustrated with the synthesis of all four possible stereoisomers of a hydroxybutenolide fragment common to murisolin and many other acetogenins. Modified dimethoxybenzyl groups with varying numbers of OEG units (-CH2CH2O-) are used to protect alcohols and serve as codes for configurations at two stereocenters. The encoded isomers are carried through several steps in a sequence of mixing prior to the reaction and then demixing during the separation to give individual pure products. A new tagging scheme is introduced in which a stereocenter bearing a hydroxy group is given two different tags. These initially redundant tags then serve to encode the configuration of another (untagged) stereocenter by appropriate pairwise reactions of the tagged precursors. The experimental features (reaction, analysis, separation, and characterization) of OEG mixture synthesis are detailed and are compared to and contrasted with those of fluorous mixture synthesis.