Synthetic studies of sumalactones A - D and Raistrickindole A

• Main Author: Pham, Thang Loi
• Other Authors: Roderick Wayland Bates
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Chemistry::Organic chemistry
• Online Access: https://hdl.handle.net/10356/164548
• Institution: Nanyang Technological University

The first chapter gives a review on natural products containing N-O bonds such as oxazine, isoxazolidine, N-hydroxypyrrole. The chapter highlights different aspects of natural product research, from the extractions of these compounds to the elucidations of their structures and synthetic techniques with the focus on identifying the challenging N-O bonds in these molecules. The chapter also spends a great part on the studies of N-hydroxydiketopiperazine natural products which are essential for the synthesis of Raistrickindole A in Chapter 3. The second chapter explores an efficient synthetic route towards sumalactones A – D which contain 10 or 11-membered ring macrolactones fused with a resorcinol aromatic ring. The strategy towards these molecules involves cross metathesis between the aromatic moiety with the alkene of a 1,3 or 1,2-diol. The macrolactones are formed by employing either Yamaguchi lactonisation or Mitsunobu reaction depending on the stereochemistry of the hydroxy group on the macrolactone ring. The third and final chapter discusses the total synthesis of Raistrickindole A whose N-O bond assignment was ambiguous which required a total synthesis for confirmation. The key step of the synthesis is the oxidative cyclisation reaction between the indole moiety and the N- hydroxyDKP using mCPBA as the oxidising reagent with unique diastereoselectivity. The N- hydroxyDKP can be synthesised asymmetrically by an intramolecular Mitsunobu reaction of a chiral hydroxamic acid.