Graduate Thesis Or Dissertation
 

Synthetic approaches to the tricarbonyl subunit of rapamycin

Public Deposited

Downloadable Content

Download PDF
https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/rx913s24j

Descriptions

Attribute NameValues
Creator
Abstract
  • Rapamycin (5) was isolated in 1975 from the soil bacteria Streptomyces hygroscopicus and its structure was determined from spectroscopic techniques and an x-ray crystallographic analysis. Although it was initially found to exhibit antibiotic activity, it was subsequently shown to possess potent immunosuppressive activity as well. Three approaches to the synthesis of the tricarbonyl subunit (C1-C15) of 5 were investigated. The first plan for the synthesis of 127 envisioned a rearrangement of the a-acyloxy amide 135 to 136 followed by oxidation. The amide 135 was synthesized by coupling of the readily prepared chloroacetylpipecolate 131 with the carboxylic acid 134. The second approach was based on a model study in which the acetylenic ester 144 was oxidized to the a,13-diketoester 146. However, synthesis of the requisite acetylenic amide precursor 150 was unsuccessful. The third approach anticipated successful formation of 167 from the aldehyde 159 and bromoacetylpipecolate 166, followed by Dess-Martin oxidation to afford the tricarbonyl subunit of rapamycin. The aldehyde was successfully prepared in ten steps from (S)-3-hydroxy-2-methylpropionate (132).
Resource Type
Date Available
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Academic Affiliation
Non-Academic Affiliation
Subject
Rights Statement
Publisher
Peer Reviewed
Language
Digitization Specifications
  • File scanned at 300 ppi (Monochrome) using ScandAll PRO 1.8.1 on a Fi-6770A in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR.
Replaces

Relationships

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details LaMunyonJamesB1998.pdf 2017-08-03 Public Download