Synthesis of (−)‐Viriditoxin: A 6,6′‐Binaphthopyran‐2‐one that Targets the Bacterial Cell Division Protein FtsZ

A twist of nature – the significance of atropisomers in biological systems

“…39 This initial publication however was quickly succeeded by a second-generation synthesis by the same group in 2012, reporting improved scalability, yields and atropselectivity. 40 Principally, the synthesis of the necessary precursor to monomer 18 (Scheme 2) was made simpler by the elimination of large-scale tin-allylation, ozonolysis and LDA-induced cyclisation steps in favour of a strategy which instead utilised aspartic acid as a chiral pool precursor, the formation and ring-opening of a chiral oxirane with a vinyl Grignard reagent, and ring-closing metathesis.…”

“…39 The achievement of the synthesis of (M)-viriditoxin has allowed for investigations into possible medicinal applications, and importantly, it has also provided a new method with which to control the atropisomerism involving relatively complex molecules with similar binaphthopyranone structures. 39,40 Subsequent to the initial studies of its cytotoxicity (LD 50 2.8 mg.kg -1 , mouse) and activation of rat ATPase, 37,41 there was little more known about the bioactivity of viriditoxin until 2013, when Foss et al reported an MIC value of 0.63 µM against B. subtillus strain 168, and determined its mechanism of action. Flow cytometry and microscopy undertaken by this group identified that, among other previously identified 'FtsZ inhibitors', viriditoxin acts by dissipating the membrane potential of bacteria, and increasing membrane permeability; not through specific in vivo FtsZ inhibition.…”

Chemical Synthesis of Complex Molecules Using Nanoparticle Catalysis

“…The formation of bi -naphthol 30 differed in the regioselectivity for oxidative coupling of 29 using homogeneous catalysis. 42–46 These intriguing observations implied subtle mechanistic variations related to specific phenol starting materials, which warranted further investigation. Besides the above notable features, the novel AgNP-catalyzed reactions showcased low catalyst loading and mild reaction conditions.…”

Synthesis of 6,6′-Binaphthopyran-2-one Natural Products: Pigmentosin A, Talaroderxines A and B

“…7 The key biaryl bond was formed via an oxidative coupling of an orthogonally protected 7-hydroxy naphthopyranone. 8 The stereochemical outcome of this reaction was subject to complete control by choice of the vanadium catalyst that was employed.…”

“…Michael-Dieckmann annulation with the lithium enolate of 5 7a proceeded smoothly with 6a and 6b to furnish 17a and 17b , respectively after oxidation. We have previously observed higher yields from this two-step process when compared to the onestep Stauton-Weinreb conditions employing β-alkoxy pyranones.…”