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Synthesis and Conformational Analysis of Model Systems of the Spirocyclic Moiety of Neaumycin B

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 (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Cinti, Nicholas A.NAC143@pitt.eduNAC1430000-0002-1768-9452
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFloreancig,
Committee MemberKoide,
Committee MemberWang,
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


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