Cinti, Nicholas A.
(2023)
Synthesis and Conformational Analysis of Model Systems of the Spirocyclic Moiety of Neaumycin B.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Neaumycin B is a potent anti-cancer agent that exhibits high selectivity toward human glioblastoma cells. The stability of this natural product, however, has made its isolation in larger quantities from natural sources difficult. A synthetic route to afford neaumycin B could aid in its isolation in appreciable amounts in order to conduct biological studies. Additionally, analogs of the macrolide could potentially be synthesized to offer improved stability while maintaining similar cytotoxicity levels. This total synthesis would need to include a method for the formation of the singly anomeric spiroketal moiety and a detailed analysis of its configuration.
This document describes the approaches taken to successfully afford and characterize models of the spirocyclic core found within neaumycin B. Models of increasing complexity were synthesized in the attempts to find the most favorable approach to afford spirocycle formation within this system. Aldol chemistry was carried out under Felkin control to afford the spirocycle precursor and set one of the stereocenters substituted on the bicyclic ring system. The results indicate that the singly anomeric spiroketal provides the most thermodynamically stable isomer, although it was shown that epimerization at the spirocenter is possible under equilibrative conditions. Conditions were formulated to deliver the desired spiroketal in a 3:1 ratio with its epimeric counterpart, going through orthogonal protecting group manipulations and cyclization in a one pot process.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
10 May 2023 |
| Date Type: |
Publication |
| Defense Date: |
13 December 2022 |
| Approval Date: |
10 May 2023 |
| Submission Date: |
30 January 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
195 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
n/a |
| Date Deposited: |
10 May 2023 17:02 |
| Last Modified: |
10 May 2023 17:02 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44146 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}