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Total Synthesis of Some Important Natural Products from Brazilian Flora
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Leonardo da Silva Neto, Breno Germano de Freitas Oliveira, Wellington Alves de Barros, Rosemeire Brondi Alves, Adão Aparecido Sabino, Ângelo de Fátima
To synthesize different eusiderins, the authors traced a strategy involving a general route, varying only the reagent used in the last step responsible for the side chain and the substituents of the attached aromatic ring. The synthesis has two key steps: the first key step is a Mitsunobu reaction between the phenolic derived from the previously synthesized o-vanillin and (S)-ethyl lactate, thus fixing the first chiral center in the structure, followed by a reduction with DIBAL at −78°C that results in the formation of aldehyde 62 (Figure 12.16), a common intermediate for the other eusiderins, which undergoes an addition of an aromatic organometallic reagent that differentiates eusiderin A 58 from eusiderin B 59; after a reduction and cyclization in Amberlyst 15, formation of the intermediate occurs (63, 64), which undergoes the second key step of eusiderin synthesis (Suzuki reaction). Then, the eusiderins are synthesized from the intermediates 63 and 64, and the boronate ester side chain derived from organoboron is used, since the Suzuki reaction is a carbon-carbon cross-coupling reaction. A disadvantage faced in the synthetic route proposed by Pilkington and Barker (2012) is the step involving the formation of the second stereogenic center of the 1,4-benzodioxane ring, wherein the cyclization generates the cis and trans isomers in a ratio of 1:5, resulting in a reduction in the reaction yield due to the need to separate the products for the last step of the synthesis.
Hydrolytic Enzymes for the Synthesis of Pharmaceuticals
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sergio González-Granda, Vicente Gotor-Fernández
It is worth mentioning that the alkyl group in the ester functionality has a dramatic influence in the selectivity displayed by the enzyme in hydrolytic processes. One clear example, is the resolution of alkyl 1,4-benzodioxan-2-carboxylates, key intermediates in the synthesis of therapeutic agents such as Piperoxan, Prosympal, Dibozane and Doxazosin (Rouf et al., 2012). Whole cells of the Arthrobacter species lipase (ABL) displayed a high selectivity in the resolution of the methyl ester using a phosphate buffer and 1-butanol as cosolvent, affording the corresponding carboxylic acid in enantiopure form after 42% conversion, while a loss of selectivity was observed in the resolution of the ethyl ester (Scheme 9.6). Influence of the alkoxy group in the KR of alkyl 1,4-benzodioxan-2-carboxylates through lipase-catalysed hydrolysis.
Radiolabeled Adrenergic and Muscarinic Blockers for in Vivo Studies
Published in William C. Eckelman, Lelio G. Colombetti, Receptor-Binding Radiotracers, 2019
WB 4101, a benzodioxan derivative available in H-3-labeled form, also appears to bind to the postsynaptic alpha receptor using the same criteria to develop a pharmacologic profile of inhibition. It binds with an affinity of 2 × 109 M−1 in the rat brain.11
Design, synthesis, and evaluation of 1, 4-benzodioxan-substituted chalcones as selective and reversible inhibitors of human monoamine oxidase B
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Zhuo Kong, Demeng Sun, Yanmei Jiang, Yun Hu
The 1, 4-benzodioxan derivatives also exhibit inhibition against MAO-B (Figure 1(B)). For example, compound 7c inhibits the hMAO-B with an IC50 value of 0.045 µM17. It is suggested that the 1, 4-benzodioxan moiety could be useful for the design of new MAO-B inhibitors