Biocatalysis and Organic Synthesis Group, ChemistryInstitute, Federal Universityof Rio de Janeiro, 21941-909, Rio de Janeiro, Brazil.
Org Biomol Chem. 2019 Feb 6;17(6):1552-1557. doi: 10.1039/c8ob03088j.
Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.
手性中间体的连续流生产在活性药物成分 (API) 构建块的开发中起着重要作用，α-氨基酸及其衍生物广泛用作构建块。在这项工作中，我们开发了两种不同的策略来合成用于合成左乙拉西坦/布瓦西坦和乙胺丁醇的中间体。所得结果表明，通过 RANEY®镍脱硫/还原策略可以将蛋氨酸甲酯连续转化为所需的乙胺丁醇中间体，而左乙拉西坦/布瓦西坦中间体可以通过 RANEY®镍（无 H2）和 Pd/C-H2 方法或光化学脱硫来合成。
