n-Pentenyl Glycosides in Organic Chemistry: A Contemporary Example of Serendipity

Recent work in our laboratory has shown that n-pentenyl glycosides (NPGs) are excellent substrates for a wide variety of reactions occurring at the anomeric center. They are prepared readily by standard glycoside forming procedures, including Fischer's direct method, and although they are stable to a wide range of reagents, they are readily activated by treatment with a halonium ion. Because of their stability and the neutral conditions for their activation, NPGs are promising substrates for a wide variety of mechanistic and synthetic studies. The effect of some of the commonly used protecting groups upon glycoside reactivity has been probed with these substrates, and the "armed/disarmed" strategy for oligosaccharide assembly emanated directly from these investigations. Thus esters disarm electronically, while benzylidene and isopropylidene rings disarm by torsional strain. However further investigations have shown that the use of N-iodosuccinimide-trifluoromethanesulfonates as the iodinating agent induces smooth reactions of the disarmed substrates. As a result, coupling procedures can be regulated either by the strategic deployment of appropriate groups, or by changing the inorganic promoter. A further level of finesse emanates from the development of procedures to convert the pentenyl group into its vicinal dibromide. These derivatives represent "blocked" NPGs since the reverse reaction is readily carried out via reductive elimination. Thus NPG activity can be sidetracked temporarily by conversion to the dibromide. Under appropriate conditions, the reaction of NPGs in acetonitrile generates acetonitrilium ions which can be trapped in situ with carboxylic acid. This has paved the way for a simple entry to glycoproteins. 1. Prologue 2. Introduction 3. Discovery 4. 4-Pentenyloxymethyl Based Protecting Groups 5. n-Pentenyl Glycosides 5.1. Synthetic Routes 6. Oxidative Hydrolysis of NPGs 7. Acetal Exchange of NPGs 8. Armed/Disarmed Coupling 9. Promoters 10. Typical Procedures for Saccharide Couplings 11. Mechanistic Questions Concerning Armed/Disarmed Effects 11.1. Rationalization 11.2. Dependence on Promoters 11.3. Sidetracking 12. NPGs as Synthons for Glycoproteins 13. Promotor-Mediated Assembly of Oligosaccharides 14. Torsion-Mediated Coupling of Saccharides 15. Epilogue