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A combination of mutasynthesis using a mutant strain of A. pretiosum blocked in the biosynthesis of amino-hydroxybenzoic acid (AHBA) and semisynthesis relying on a Stille cross-coupling step provided access to new ansamitocin derivatives of which one was attached by a thermolabile linker to nanostructured iron oxide particles. When exposed to an oscillating electromagnetic field the resulting iron oxide/ansamitocin conjugate 19 heats up in an aqueous suspension and the ansamitocin derivative 16 is released by means of a retro-Diels-Alder reaction. It exerts strong antiproliferative activity (IC 50 =4.8 ng mg -1 ) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Current research indicates that anthocyanins are primarily degraded to form phenolic acid products. However, no studies have yet demonstrated the metabolic conjugation of these anthocyanin-derived phenolic acids in humans., Methods and Results: Within the present study, a simulated gastrointestinal digestion model was used to evaluate the potential degradation of anthocyanins post-consumption. Subsequently, cyanidin (Cy) and pelargonidin and their degradation products, protocatechuic acid and 4-hydroxybenzoic acid, were incubated in the presence of human liver microsomes to assess their potential to form hepatic glucuronide conjugates. For structural conformation, phenolic glucuronides were chemically synthesised and compared to the microsomal metabolites. During the simulated gastric digestion, anthocyanin glycosides (200 μM) remained stable however their aglycone derivatives were significantly degraded (20% loss), while during subsequent pancreatic/intestinal digestion only pelargonidin-3-glucoside remained stable while cyanidin-3-glucoside (30% loss) and Cy and pelagonidin aglycones were significantly degraded (100% loss, respectively). Following microsomal metabolism, pelargonidin formed 4-hydroxybenzoic acid, which was further metabolised (65%) to form two additional glucuronide conjugates, while Cy formed protocatechuic acid, which was further metabolised (43%) to form three glucuronide conjugates., Conclusions: We propose that following ingestion, anthocyanins may be found in the systemic circulation as free or conjugated phenolic acids, which should be a focus of future dietary interventions., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An extremophilic challenge: Stereospecific condensation of a fully functionalized ketal aldehyde and a 2,6-dihydroxybenzoic acid is the key step in the synthesis of (-)-berkelic acid confirming Fürstner's reassignment of the stereochemistry at C18 and C19, establishing the absolute stereochemistry, and tentatively assigning the stereochemistry at C22.

Total syntheses of (-)-balanol and all of its stereoisomers starting from easily available Garner aldehydes are described. Diastereoselective Grignard reactions on Garner aldehydes and ring-closing metatheses are the key steps for the construction of hexahydroazepine subunits. The benzophenone subunits were constructed through coupling of suitably functionalized aromatic aldehyde and bromo components. The synthetic route constitutes a convenient and scalable reaction sequence to generate all of the stereoisomers of balanol. The methodology is explored further for the synthesis of N-tosyl analogues of balanol and of fully protected ophiocordin.

A molecular recognition study of 3,5-dihydroxybenzoic acid (1) and its bromo derivative 4-bromo-3,5-dihydroxybenzoic acid (2) with the N-donor compounds 1,2-bis(4-pyridyl)ethene (bpyee), 1,2-bis(4-pyridyl)ethane (bpyea), and 4,4'-bipyridine (bpy) is reported. Thus, the syntheses and structural analysis of molecular adducts 1 a-1 c (1 with bpyee, bpyea, and bpy, respectively) and 2 a-2 c (2 with bpyee, bpyea, and bpy, respectively) are discussed. In all these adducts, recognition between the constituents is established through either O--H...N and/or O--H...N/C--H...O pairwise hydrogen bonds. In all the adducts both OH and COOH functional groups available on 1 and 2 interact with the N-donor compounds, except in 2 a, in which only COOH (COO-) is involved in the recognition process. The COOH moieties in 1 a, 1 b, and 2 b form only single O--H...N hydrogen bonds, whereas in 1 c and 2 c, they form pairwise O--H...N/C--H...O hydrogen bonds. In addition, subtle differences in the recognition patterns resulted in the formation of cyclic networks of different dimensions. In fact, only 1 c forms a four-molecule cyclic moiety, as was already documented in the literature for this kind of assemblies. All complexes have been characterized by single-crystal X-ray diffraction. The supramolecular architectures are quite elegant and simple, with stacking of sheets in all adducts, but a rather complex network with a threefold interpenetration pattern was found in 2 c.