Synthetic studies on the pederin family of antitumour agents. Syntheses of pederin, mycalamide B and analogues

Narquizian, Robert (2000) Synthetic studies on the pederin family of antitumour agents. Syntheses of pederin, mycalamide B and analogues. PhD thesis, University of Glasgow.

Abstract

A general modular approach to members of the pederin family of antitumour agents, exemplified by syntheses of pederin (1.1), mycalamide B (1.5) and analogues (17-epi-1.5, 2.8, 2.9 and 2.10), is described. The common strategy makes use of a metallated dihydropyran approach to couple two advanced fragments. All 6 compounds are prepared from 6-lithio-2,3-dimethyl-4-phenylselenomethyl-3,4-dihydro-2H-pyran 1.59 and 2-(3- chloropropyl)-3,3-dimethyl-3,4-dihydro-2H-pyran-4-one 2.4. The key steps in the synthesis of pederin 1.1 or its analogues are Sharpless asymmetric dihydroxylations and a rhodium-catalysed directed reduction of an acylimidate. The key steps in the synthesis of the right fragment of mycalamide B 1.5 are a P2O5-mediated formation of the trioxadecalin ring, a Meerwein-Pondorf-Verley reduction to install the C13-stereogenic centre, installation of the C10-N bond in good yield and total stereocontrol at the C10 centre via a Curtius rearrangement and/or a Hofmann rearrangement, as well as Sharpless asymmetric dihydroxylations.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Pharmacology, organic chemistry.
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Kocienski, Professor Philip J.
• Date of Award: 2000
• Depositing User: Enlighten Team
• Unique ID: glathesis:2000-71252
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 May 2019 10:49
• Last Modified: 02 Nov 2022 20:33
• Thesis DOI: 10.5525/gla.thesis.71252
• URI: https://theses.gla.ac.uk/id/eprint/71252