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Updated: Aug 6, 2026

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling
Published on: December 18, 2017
Selective epimerization of rapamycin via a retroaldol/aldol mechanism mediated by titanium tetraisopropoxide
1ARIAD Gene Therapeutics, Inc, Cambridge, Massachusetts 02139-4234, USA.
Abstract:
We describe the efficient and selective epimerization of the immunosuppressant rapamycin to 28-epirapamycin under mild conditions. The mechanism of epimerization involves an equilibrium of the four C28/C29 diastereomers through a two-step retroaldol/aldol (macrocycle ring-opening/ring-closing) sequence. This retroaldol/aldol equilibration is not restricted to rapamycin but is also applicable to acyclic beta-hydroxyketones. A potentially useful extension of the method--the use of beta-hydroxyketones as enolate synthons for effecting inter- or intramolecular aldol reactions under neutral conditions--is demonstrated.
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