18O/16O‐Encoding Strategy for Microscale Stereochemical Determination of Peptidic Natural Products. Issue 17 (16th July 2021) - Takeuchi, Aoi
Abstract: The demand for more efficient methods of establishing the undetermined stereochemistries of peptidic natural products continues unabated. A new method for microscale stereochemical determination was devised by integrating solid‐phase synthesis, split‐and‐mix randomization, 18 O/ 16 O‐encoding of d /l ‐configurations, tandem mass spectrometry, and biological evaluation. Here we applied gramicidin A as the molecule for a blind test. Gramicidin A and its 31 diastereomers were randomly prepared in microgram scale with 18 O/ 16 O‐stereochemical encoding and subjected to MS/MS‐structural determination and cytotoxicity assay. Only the parent gramicidin A was selected from among the 32 stereoisomers, validating the high reliability of the present strategy. Abstract : A novel 18 O/ 16 O‐encoding strategy for microscale stereochemical determination of peptidic natural products has been devised. The strategy integrates the one‐bead‐one‐compound (OBOC) strategy, 18 O/ 16 O‐stereochemical encoding, tandem mass (MS/MS) spectrometry, and biological evaluation. Its application enabled the correct identification of gramicidin A from 32 stereoisomers randomly prepared in microgram scale, thereby validating the high reliability.