386 How Do N-Acylnitroindolines Photoacylate Glycosylamines? A Semiempirical Computational Approach

Friday, November 6, 2009: 4:20 PM
Angus (Camino Real Hotel)
Jose E. Mendez , Department of Chemistry, University of Texas at El paso, El paso, TX
Nathan J. Westfall , Department of Chemistry, University of Texas at El paso, El paso, TX
Katja Michael , Department of Chemistry, University of Texas at El paso, El paso, TX
Carl W. Dirk , Department of Chemistry, University of Texas at El paso, El paso, TX
Recently, a photochemical acylation method first discovered in the late 70’s, has remerged and has proven particularly useful for the synthesis of N-glycopeptides.  The method relies on the unusual properties of N-acyl-7-nitroindolines, which can be activated with UV-light (absorption maximum ~ 350 nm).  To date, the mechanism by which the photoactivation occurs is still unclear.   It is known that two different photolysis pathways exist depending on the reaction conditions.  One leads to the desired acylation of a glycosylamine, while the other leads to an undesired free carboxylic acid.  Understanding the mechanism of the photoactivation and the fate of the photoreactive species has major implications on biasing the outcome of the photoreaction toward N-acylation.
In this investigation, semi-empirical computational methods were used to explore the potential energy surface (PES) of the photoactivation to locate transition states and intermediates. The potential energy surface of singlet excited (S1), ground state (S0) and triplet ground state (T0) were studied in detail. Our analysis supports a one step reaction mechanism, involving a 1,5-sigmatrophic rearrangement, moreover, crossing of PES seems to play an important role in the reaction.  Furthermore, a mechanism is proposed for the decomposition of the activated species to the undesired product.  This mechanism is consistent with a recent experiment involving 18O water.