Gruber Christian C, Oberdorfer Gustav, Voss Constance V, Kremsner Jennifer M, Kappe C Oliver, Kroutil Wolfgang
Institute of Chemistry and Christian Doppler Laboratory for Microwave Chemistry (CDLMC), Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
J Org Chem. 2007 Jul 20;72(15):5778-83. doi: 10.1021/jo070831o. Epub 2007 Jun 20.
An easy to use computerized algorithm for the determination of the amount of each labeled species differing in the number of incorporated isotope labels based on mass spectroscopic data is described and evaluated. Employing this algorithm, the microwave-assisted synthesis of various alpha-labeled deuterium ketones via hydrogen-deuterium exchange with deuterium oxide was optimized with respect to time, temperature, and degree of labeling. For thermally stable ketones the exchange of alpha-protons was achieved at 180 degrees C within 40-200 min. Compared to reflux conditions, the microwave-assisted protocol led to a reduction of the required reaction time from 75-94 h to 40-200 min. The alpha-labeled deuterium ketones were reduced by biocatalytic hydrogen transfer to the corresponding enantiopure chiral alcohols and the deconvolution algorithm validated by regression analysis of a mixture of labeled and unlabeled ketones/alcohols.
本文描述并评估了一种易于使用的计算机算法，该算法可根据质谱数据确定基于掺入同位素标记数量不同的每种标记物种的量。采用该算法，通过与氧化氘进行氢-氘交换，对各种α-标记氘代酮的微波辅助合成在时间、温度和标记程度方面进行了优化。对于热稳定的酮，在180℃下40 - 200分钟内实现了α-质子的交换。与回流条件相比，微波辅助方案将所需反应时间从75 - 94小时减少到40 - 200分钟。通过生物催化氢转移将α-标记氘代酮还原为相应的对映体纯手性醇，并通过对标记和未标记酮/醇混合物的回归分析验证了去卷积算法。
