title: Spiroligozymes for transesterifications: design and relationship of structure to activity.
abstract: Transesterification catalysts based on stereochemically defined, modular, functionalized ladder-molecules (named spiroligozymes) were designed, using the "inside-out" design strategy, and mutated synthetically to improve catalysis. A series of stereochemically and regiochemically diverse bifunctional spiroligozymes were first synthesized to identify the best arrangement of a pyridine as a general base catalyst and an alcohol nucleophile to accelerate attack on vinyl trifluoroacetate as an electrophile. The best bifunctional spiroligozyme reacted with vinyl trifluoroacetate to form an acyl-spiroligozyme conjugate 2.7 × 10(3)-fold faster than the background reaction with a benzyl alcohol. Two trifunctional spiroligozymes were then synthesized that combined a urea with the pyridine and alcohol to act as an oxyanion hole and activate the bound acyl-spiroligozyme intermediate to enable acyl-transfer to methanol. The best trifunctional spiroligozyme carries out multiple turnovers and acts as a transesterification catalyst with k(1)/k(uncat) of 2.2 × 10(3) and k(2)/k(uncat) of 1.3 × 10(2). Quantum mechanical calculations identified the four transition states of the catalytic cycle and provided a detailed view of every stage of the transesterification reaction.
authors.affiliation: Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Kheirabadi
authors.forename: Nihan
authors.initials: N
authors.lastname: Çelebi-Ölçüm
authors.forename: Matthew F L
authors.initials: MF
authors.lastname: Parker
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Zhao
authors.forename: Gert
authors.initials: G
authors.lastname: Kiss
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Christian E
authors.initials: CE
authors.lastname: Schafmeister
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D055162:Biocatalysis; D040761:Biomimetic Materials / Q000737:chemistry*; D002384:Catalysis; D004951:Esterification; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D000438:Alcohols; D011725:Pyridines; D014753:Vinyl Compounds; C528648:vinyl trifluoroacetate; D000432:Methanol