title: Selective epimerization of rapamycin via a retroaldol/aldol mechanism mediated by titanium tetraisopropoxide.
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.
authors.affiliation: ARIAD Gene Therapeutics, Inc, Cambridge, Massachusetts 02139-4234, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: C A
authors.initials: CA
authors.lastname: Digits
authors.forename: M
authors.initials: M
authors.lastname: Hatada
authors.forename: S
authors.initials: S
authors.lastname: Narula
authors.forename: L W
authors.initials: LW
authors.lastname: Rozamus
authors.forename: C M
authors.initials: CM
authors.lastname: Huestis
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: D
authors.initials: D
authors.lastname: Dalgarno
authors.forename: D A
authors.initials: DA
authors.lastname: Holt
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002384:Catalysis; D007166:Immunosuppressive Agents / Q000737:chemistry*; D009942:Organometallic Compounds; D020123:Sirolimus / Q000737:chemistry*; D013237:Stereoisomerism; D014025:Titanium
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D009942:Organometallic Compounds; C102815:titanium isopropoxide; D014025:Titanium; D020123:Sirolimus