Development of synthetic organic chemistry methods to selectively transform steroid derivatives to access known metabolites and impurities, and novel drug-like structures

道尔顿医药服务公司是一家领先的制药产品制造商，为制药和生物技术行业提供分析服务。道尔顿对类固醇化合物特别感兴趣，因为客户的研究和开发需求对标准、代谢物和杂质的需求很高。他们目前正面临着有效地制造某些类别的类固醇化合物的技术问题。道尔顿制药公司和莱尔森大学的马克·J·阿德勒教授的实验室合作的这个项目试图发现新的化学方法来选择性地转化包括类固醇在内的生物感兴趣的分子。具体目标是开发高度特异的方法将酮还原为仲醇，允许区分具有相似反应性特征的类固醇分子中的两个酮；这种选择性反应性对于制造类固醇类似物的特定子集至关重要。目前的分化需要多步骤的合成过程，导致大量的化学浪费，耗时长，产品收率下降。我们的目标是直接区分这两个官能团进行化学转化，从而提供一条更有效、更绿色的途径来获得所需的产品。这类产品包括已知的药物代谢物和杂质。这种方法还可以方便地获得新的生物活性分子，作为潜在的探针或治疗药物进行评估。该合作项目将培养两名硕士研究生，他们将与道尔顿制药公司的科学家密切合作，开发创新的、与工业相关的化学合成方法。

Dalton Pharma Services is a leading manufacturer of pharmaceutical products and provider of analytical services to the pharmaceutical and biotechnological industries. Dalton is particularly interested in steroid compounds because of the high demand for standards, metabolites, and impurities from customers for their research and development needs. They are currently facing a technological problem in efficiently making certain classes of steroid compounds.This collaborative project between Dalton Pharma and Prof. Marc J. Adler's lab at Ryerson University seeks to discover new chemical methods to selectively transform molecules of biological interest, including steroids. The specific goal is to develop highly specific ways to reduce ketones to secondary alcohols, allowing for the differentiation of two ketones in a steroid molecules with similar reactivity profiles; this selective reactivity is vital to make particular subsets of steroid analogues. Currently differentiation requires a multi-step synthetic process, resulting in significant chemical waste, expenditure of time, and decrease in product yield. We aim to directly differentiate the two functional groups for chemical transformation, thus providing a more efficient and greener path to the desired products. Such products include known metabolites of and impurities in drugs. This method will also provide ready access to new bioactive molecules to be evaluated as potential probes or therapeutics. The collaborative project will train two Master's students who will develop innovative and industrially relevant chemical synthesis methods in close collaboration with Dalton Pharma scientists.