Studies on a biomimetic oxidative dimerization approach to the hibarimicins

Abstract

Nature utilizes dimerization as a method of producing structurally complex metabolites. The microbial metabolites known collectively as the hibarimicins are one example of complex natural products produced biosynthetically by dimerization of a phenolic aromatic polyketide. Described in this communication are model studies aimed at demonstrating regiocontrolled oxidative dimerization of phenolic ring systems related to the biosynthetic precursor of the hibarimicin family of natural products.

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

“…28 It was recently discovered by Bara et al that the Talaromyces wortmannii fungus, an endosymbiont of Egyptian Aloe vera (Asphodeloideae), contained several bioactive atropisomeric compounds; and the group conducted extremely extensive studies to determine any potential medicinal application. 29 Analysis of the isolated products 26 found that they were similar to that of previously-reported flavomannin, 30 allowing for general structural assignment ( Figure 5, Compounds 11 and 12). HR-ESI/MS revealed an identical molecular composition for both compounds (C 30 H 26 O 10 ), and near identical UV absorption maxima.…”

“…25 There are ongoing studies towards a biomimetic synthesis utilising oxidative dimerization of the hibarimicins, though these have thus far proven unsuccessful. 26 The extracted compounds (Hibarimicins A, B, C, D and G) were screened for inhibition of calmodulin-dependent protein kinase III (CAMKIII), protein kinase A (PKA), protein kinase C (PKC), and protein tyrosine kinase (PTK). All of the natural molecules had potent PTK and CAMKIII inhibition, though showing little inhibition of both PKA and PKC, indicating specificity to the PTK protein.…”

Co-culture of the fungusFusarium tricinctumwithStreptomyces lividansinduces production of cryptic naphthoquinone dimers

“…22 In the biosynthesis of xanthomegnin, the optically active monomers are formed rst and are then dimerized by oxidative coupling. 23 Compound 5 showed UV absorption maxima at 350, 263, 243 and 229 nm and had the molecular formula C 15 H 12 O 8 based on the HRESIMS data. Compound 5 contains two additional protons compared to the co-isolated structurally related known compound lateropyrone (6), 24 suggesting hydrogenation of the olenic double bond of 6 at C-8 and 9, thus yielding 5.…”

“…Fr.4 was further fractionated using a Sephadex LH-20 column with MeOH as mobile phase which yielded compound 1 (10.8 mg) as the subfraction Fr. 23 D 0 (c 0.1, DCM); UV (MeOH) l max 223, 277 and 320 nm; 1 H and 13 C NMR data see…”

Laccase-mediated synthesis of bioactive natural products and their analogues

“…A less environmentally friendly methodology is based on the use of oxidizing agents such as Ag 2 O, FeCl 3 , MnO 2 and others. [70][71][72][73][74][75] Both methods mimic the biosynthetic pathway, as the key step is based on the oxidative coupling of radicals. If regioselectivity during radical coupling may be in part controlled by thermodynamically favoured mesomeric structures or by steric hindrance effects, enantioselectivity is not energetically discriminated.…”