title: Total synthesis of cryptophycin-24 (Arenastatin A) amenable to structural modifications in the C16 side chain.
abstract: Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: M
authors.initials: M
authors.lastname: Eggen
authors.forename: C J
authors.initials: CJ
authors.lastname: Mossman
authors.forename: S B
authors.initials: SB
authors.lastname: Buck
authors.forename: S K
authors.initials: SK
authors.lastname: Nair
authors.forename: L
authors.initials: L
authors.lastname: Bhat
authors.forename: S M
authors.initials: SM
authors.lastname: Ali
authors.forename: E A
authors.initials: EA
authors.lastname: Reiff
authors.forename: T C
authors.initials: TC
authors.lastname: Boge
authors.forename: G I
authors.initials: GI
authors.lastname: Georg
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D047630:Depsipeptides; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C096566:arenastatin A