First Application of the Dakin-West Reaction to Fmoc Chemistry: Synthesis of the ketomethylene tripeptide Fmoc-Nα-Asp(tBu)-(R,S)Tyr(tBu)ψ(CO-CH2)Gly-OH

Abstract

A practical synthesis of a tripeptide containing a ketomethylene isostere, suitably protected for introduction in Fmoc SPPS, has been carried out for the first time in Fmoc chemistry by using a modified Dakin-West reaction.

Monosuccinate ester of melampomagnolide B

“…For the isolation of a similar compound, see: El-Feraly (1984). For the structures and syntheses of similar compounds, see: Gonzalez et al (1988); Macias et al (1992); Casimir et al (1995). Refinement progress was checked using routines in PLATON (Spek, 2009) and by the R-tensor (Parkin, 2000) The crystal was placed directly into the cold stream of a liquid nitrogen based cryostat, according to published methods, see: Hope (1994); Parkin & Hope (1998).…”

“…More importantly, from a drug design point of view, MMB is a more interesting molecule because it contains an OH group, which provides the means for designing pro-drugs with improved water solubility, bioavailability and tissue targeting. In the current study we synthesized a mono succinate derivative of MMB by the reaction of MMB with succinic anhydride (Casimir et al 1995). The compound obtained was recrystallized from a mixture of 9:1 dichloromethane and methanol.…”

N-(2-Methyl-3-oxo-1,3-diphenylpropyl)acetamide

“…For the biological properties of N-(2-methyl-3-oxo-1,3diphenylpropyl)acetamide derivatives, see: Barluenga et al (1993); Casimir et al (1995) and for their synthesis, see: Dakin & West (1928); Selvam & Perumal (2009); Heravi et al (2009).…”

One-Pot Synthesis ofβ-Acetamido Ketones Using Boric Acid at Room Temperature

“…β -acetamido ketones are versatile intermediates in that their skeletons exist in a number of biologically or pharmacologically important compounds [4]. The best known route for the synthesis of these compounds is the Dakin-West reaction [5], which involves the condensation of an amino acid with acetic anhydride in the presence of a base via an intermediate azlactone to give the acetamido ketones [6].…”