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Mixture synthesis of a 16-member Murisolin stereoisomer library &synthesis of C1-C20 and C21-C40 fragments of Tetrafibricin

Gudipati, Venugopal (2008) Mixture synthesis of a 16-member Murisolin stereoisomer library &synthesis of C1-C20 and C21-C40 fragments of Tetrafibricin. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Chapter 1 of this thesis describes two new strategies for the solution phase mixture synthesis: OEG-mixture synthesis (OMS) and OEG-fluorous mixture synthesis (OFMS). An OEG-mixture synthesis of four stereoisomers of the hydroxybutenolide unit of murisolin was pursued. A strategy for solution phase stereoisomer synthesis based on orthogonal separation tagging and double demixing was implemented with fluorous (fluoroalkyl) and oligoethylene glycol (OEG, [OCH2CH2]n) tags. A mixture of four stereoisomers of a dihydroxytetrahydrofuran subunit encoded by fluorous tags was coupled by a Kocienski-Julia olefination to a mixture of four stereoisomers of the hydroxybutenolide subunit encoded by OEG tags. An orchestrated sequence of reduction (1x), OEG demixing (1x), fluorous demixing (4x) and detagging (16x) provided sixteen stereoisomers of murisolin. Through this double tagging strategy, the configuration of sixteen compounds was encoded with only eight tags.Chapter 2 describes the synthesis of the C1-C20 and C21-C40 fragments of the natural product tetrafibricin. A convergent synthesis of the proposed structure of tetrafibricin has been explored. In this approach, we envisioned a series of the Kocienski-Julia olefination reactions with appropriate aldehydes and sulfones to afford fragments C35-C40, C31-C35 and C21-C30. The synthesis of the C35-C40 fragment has been achieved in 11 steps starting with the commercially available pent-4-en-1-ol in an overall 25% yield. The synthesis of the C31-C34 fragment commenced with the commercially available (S)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol in 5 steps in an overall 46% yield. 16 steps are implemented in the synthesis of the C21-C30 fragment in a 4.5% overall yield. The synthesis of the C14-C20 fragment was achieved in 10 steps in an overall 23% yield. A synthesis of the C9-C13 fragment was established in 5 steps in 37% overall yield. The synthesis of the C1-C8 fragment was pursued in 8 steps in an overall 22% yield. The assembly of the C1-C8, C9-C13 and C14-C20 fragments was performed to afford the C1-C20 fragment. The C21-C30, C31-C34 and C35-C40 fragments were assembled by a Kocienski-Julia olefination to form the C21-C40 fragment of tetrafibricin.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCurran, Dennis Pcurran@pitt.eduCURRAN
Committee MemberDay, Billybday@pitt.eduBDAY
Committee MemberWilcox, Craigdaylite@pitt.eduDAYLITE
Committee MemberWipf, Peterpwipf@pitt.eduPWIPF
Date: 12 June 2008
Date Type: Completion
Defense Date: 17 December 2007
Approval Date: 12 June 2008
Submission Date: 21 April 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: double mixture synthesis; fluorous mixture synthesis; OEG-fluorous mixture synthesis; oligoethyleneglycol mixture synthesis; stereoisomer library; tetrafibricin; Mixture synthesis; murisolin
Other ID:, etd-04212008-115104
Date Deposited: 10 Nov 2011 19:40
Last Modified: 15 Nov 2016 13:41


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