ABSTRACT
Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these molecules, brought together by a weak and reversible aminal "connection", was found to be an important element of reactivity control. We present evidence that reversible dimer dissociation is instrumental in aziridine aldehyde transformations. We anticipate further developments that will unveil other synthetic consequences of remote control of selectivity through forging reversible covalent interactions.
Subject(s)
Aldehydes/chemical synthesis , Aziridines/chemical synthesis , Aldehydes/chemistry , Aziridines/chemistry , Dimerization , Molecular Conformation , StereoisomerismABSTRACT
Due to recent advances in high throughput organic synthesis, discovery teams now need to profile increased numbers of analogs in vitro for their absorption, distribution, metabolism, and excretion (ADME) properties. Consequently, pharmaceutical companies are developing lower cost and higher throughput methods for ADME testing. As demands for metabolic stability testing have increased in our laboratory, the time required to analyze samples using high-pressure liquid chromatography-mass spectrometry (HPLC-MS) has grown rapidly and ultimately limited our data output. In this study we show that solid phase extraction-mass spectrometry (SPE-MS) is a viable alternative to HPLC-MS for monitoring small molecule stability in liver microsomes. Using the SPE-MS approach, samples can be analyzed in 24 s compared to 2.5 min on the HPLC-MS without compromising data quality, thereby alleviating the analytical bottleneck.