Occurrence and risk assessment of fluoroquinolones and tetracyclines in cultured fish from a coastal region of northern China.

Occurrence and levels of 11 fluoroquinolones (FQs) and four tetracyclines (TC) in 14 cultured fish species from a coastal city in the northern China were investigated. Five FQs (ofloxacin, enoxacin, ciprofloxacin, enrofloxacin, and sarafloxacin) and oxytetracycline were detected. Lower detection frequencies of antibiotics were observed in the marine fish. The concentrations of ΣFQs ranged from not detectable (nd) to 130 ng/g wet weight (ww) (median, 7.2 ng/g ww), and the concentration range of ΣTCs was nd to 200 ng/g ww (median, nd ng/g ww). The Chinese snakehead contained the highest concentrations of ΣFQs (130 ng/g ww) and the small yellow croaker accumulated the highest concentrations of ΣTCs (200 ng/g ww), respectively. Although the calculated estimated daily intakes (EDI) suggested that the consumption of these cultured fish from this region was not associated with significant human health risks, this study provides useful information that will be helpful in the appropriate antibiotic use in aquaculture. To our knowledge, this can be the first report on the occurrence and levels of antibiotics in cage-cultured marine fish from the Bohai Rim region, China.

Total synthesis of bryostatins: the development of methodology for the atom-economic and stereoselective synthesis of the ring C subunit.

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins.

Atom-economic and stereoselective syntheses of the ring a and B subunits of the bryostatins.

This article describes chemoselective and atom-economic methods for the stereoselective assembly of the ring A and B subunits of bryostatins. A Ru-catalyzed tandem alkene-alkyne coupling/Michael addition reaction was developed and applied to the synthesis of bryostatin ring B. We explored an acetylide-mediated epoxide-opening/6-exo-dig cyclization route to access the bryostatin ring A, although ring A was eventually furnished through an acid-catalyzed tandem transketalization/ketalization sequence. In addition, a dinuclear zinc-catalyzed methyl vinyl ketone (MVK) aldol strategy was evaluated for the construction of the polyacetate moiety. Utilization of these methods ultimately led to the rapid assembly of the northern bryostatin fragment containing both the ring A and B subunits.

Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches.

Of the concepts used to improve the efficiency of organic syntheses, two have been especially effective: atom economy (the use of routes in which most of the atoms present in the reactants also end up in the product) and chemoselectivity (the use of reactions that take place only at desired positions in a molecule). Synthesis of complex natural products is the most demanding arena in which to explore such principles. The bryostatin family of compounds are especially interesting targets, because they combine structural complexity with promising biological activity. Furthermore, synthetic routes to some bryostatins have already been reported, providing a benchmark against which new syntheses can be measured. Here we report a concise total synthesis of bryostatin 16 (1), a parent structure from which almost all other bryostatins could in principle be accessed. Application of atom-economical and chemoselective reactions currently under development provides ready access to polyhydropyran motifs in the molecule, which are common structural features of many other natural products. The most notable transformations are two transition-metal-catalysed reactions. The first is a palladium-catalysed reaction of two different alkynes to form a large ring. The product of this step is then converted into a dihydropyran (the 'C ring' of bryostatins) in the second key reaction, which is catalysed by a gold compound. Analogues of bryostatin that do not exist in nature could be readily made by following this route, which might allow the biological activity of bryostatins to be fine-tuned.