Synthesis of Benzylic Functionalised Ether Linked Series
The OHOH compounds originated from a potent lead produced during a Pfizer biosynthesis. The chemistry lab synthesis is fairly lengthy at six steps from a common intermediate.
The synthesis starts with the diol protection of Tris to give 1 followed by oxidative cleavage to the ketone 2. The appropriate Grignard reagent is then prepared and reacted with 2 to give. This then needs to be deprotected, and subsequently reportected to leave one of the secondary alcohols free, compound 5. Compound 5 is then reacted with the core using the NaH method to give the protected-OHOH. Deprotection using HCl gives the final OHOH compound.
ELN link for the synthesis of the phenyl, 3,4-difluoro and N-dimethylaniline.
Attempts to use the unprotected triol, 4, directly in the substitution step were unsuccessful, with a number of unstable side-products produced.