Total synthesis of Galbulimima alkaloids. Resin-bound glycosyl phosphates as glycosyl donors.

• Main Author: Hunt, Diana Katharine
• Other Authors: Mohammad Movassaghi and Peter H. Seeberger.
• Format: Others
• Language: English
• Published: Massachusetts Institute of Technology 2007
• Subjects: Chemistry.
• Online Access: http://hdl.handle.net/1721.1/38321

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006. === Vita. === Includes bibliographical references. === I. Total Synthesis of Galbulimima Alkaloids. The total synthesis of enantiomerically enriched (+)- and (-)-galbulimima alkaloid 13 is outlined. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB ring system and masked the C16-carbonyl as an N-vinyl carbamate for late stage oxidative unveiling as the corresponding C16-enone. Completely diastereoselective introduction of the C-ring via radical cyclization chemistry followed by an enamine-ketone addition for construction of the CDE-ring system allowed rapid entry to the pentacyclic core of these alkaloids. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is now unambiguously revised to 2S. === (cont.) II. Resin-bound Glycosyl Phosphates As Glycosyl Donors. Resin-bound glycosyl phosphates were readily accessed on solid support via a three step procedure from support-bound glycals. These resin-bound glycosyl phosphates were successfully used as glycosylating agents for coupling with a series of solution based nucleophiles. The stereochemical outcome of disaccharide formation was dependent on the nature of the linker connecting the saccharide to the polymer. Interestingly, other glycosyl donors such as thioglycosides and trichloroacetimidates did not exhibit this dependence, indicating a different reaction mechanism for glycosylation. III. A Modular Synthesis of FGF-2 Binding Heparin Pentasaccharide. A modular synthesis of FGF-2 binding heparin pentasaccharide is outlined. The synthetic strategy utilizes a disaccharide trichloroacetimidate donor and a uronic acid acceptor as building blocks designed for later application to a fully automated synthesis. === by Diana Katharine Hunt. === Ph.D.