Studies towards the total synthesis of ristocetin A and orienticin C aglycones.

摘要

Vancomycin-related glycopeptides constitute a large family of clinically important antibiotics, used as drugs of last resort in treating infections caused by methicillin-resistant Staphylococcus aureus. However, the frequency of vancomycin resistant pathogens has increased significantly over the past decade, prompting an interest in the development of synthetic and semi-synthetic glycopeptides.; The research work presented in this thesis has been focused on the application of ruthenium-mediated SNAr methodology for the synthesis of diaryl ether linkages both inter- and intramolecularly. As described in chapter two, our efforts first targeted the synthesis of the F-O-G subunit 2.8 of ristocetin A via an intermolecular SNAr reaction between the phenolic OH of the Teoc protected F amino alcohol 2.9 and the chloro substituent of the amino alcohol corresponding to G ring 2.10 . Considerable competing demetalation of the starting material G-ruthenium complex 2.10 occurred during the attempted coupling, which was overcome by stepwise addition of the solid G-ruthenium complex 2.10 to the reaction mixture increasing the yield of this transformation to 66% yield.*; Chapter three provides details for the construction of the intermediate 3.3, a tripeptido-arene-ruthenium complex, required for a projected synthesis of orienticin C aglycone 3.1.*; Also, a model study on ruthenium-mediated macrocyclization for the formation of the 16-membered diaryl ether ring 3.32 was investigated, assuring the applicability of this approach to the synthesis of orienticin C aglycone.*; *Please refer to dissertation for diagrams.