Enantio- and stereoselective route to the phoslactomycin family of antibiotics: formal synthesis of (+)-fostriecin and (+)-phoslactomycin B

Abstract

A general methodology applicable for the synthesis of the phoslactomycin family of antibiotics, potent and selective protein phosphatase inhibitors, has been developed starting from a beta-isocupreidine-catalyzed asymmetric Baylis-Hillman reaction of 3-(4-methoxybenzyloxy)propanal with hexafluoroisopropyl acrylate, and thereby formal syntheses of (+)-fostriecin and (+)-phoslactomycin B have been accomplished.

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

“…Worth mentioning are also phoslactomycin B 92 and leustroducsin B 93, produced by Streptomyces platensis. RCM of acrylates was the key step to build the pentenolide subunit in many formal and total syntheses of fostriecin 90 [156][157][158][159][160], as well as in the preparation of cytostatin 91 [161], phoslactomycin B 92 [162][163][164], and leustroducsin B 93 [67] (Scheme 33).…”

Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products

“…115 The same intermediate used in Hatakeyama’s 2009 synthesis of fostriecin (vide supra) was used to complete a synthesis of phoslactomycin B ( 7 ) as well. The advanced intermediate epoxide 135 was opened with cyanide (rather than hydride) to give a precursor to the C8 aminoethyl group of phoslactomycin B (Figure 34).…”

De novo synthesis of natural products via the asymmetric hydration of polyenes

“…Fostriecin’s potential use as a chemotherapeutic agent has inspired many more total syntheses. 66,67 …”