[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Dipterocarps protected by Jering local wisdom in Jering Menduyung Nature Recreational Park, Bangka Island, Indonesia

Apart of the oil palm plantation expansion, the Jering Menduyung Nature Recreational Park has relatively diverse plants. The 3,538 ha park is located at the north west of Bangka Island, Indonesia. The minimum species-area curve was 0.82 ha which is just below Dalil conservation forest that is 1.2 ha, but it is much higher than measurements of several secondary forests in the Island that are 0.2 ha. The plot is inhabited by more than 50 plant species. Of 22 tree species, there are 40 individual poles with the average diameter of 15.3 cm, and 64 individual trees with the average diameter of 48.9 cm. The density of Dipterocarpus grandiflorus (Blanco) Blanco or kruing, is 20.7 individual/ha with the diameter ranges of 12.1 – 212.7 cm or with the average diameter of 69.0 cm. The relatively intact park is supported by the local wisdom of Jering tribe, one of indigenous tribes in the island. People has regulated in cutting trees especially in the cape. The conservation agency designates the park as one of the kruing propagules sources in the province. The growing oil palm plantation and the less adoption of local wisdom among the youth is a challenge to forest conservation in the province where tin mining activities have been the economic driver for decades. More socialization from the conservation agency and the involvement of university students in raising environmental awareness is important to be done