Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639120
Title: Asymmetric synthesis of lignans
Author: Storer, N. P.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1994
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Abstract:
An introduction to lignans, including classification, occurrrence, biological activity, the role of lignans and their biosynthesis, is described in chapter 1. Chapter 2 presents a review of the conjugate addition reaction, with particular emphasis on chiral conjugate additions. This chapter also reviews the synthesis of lignans via conjugate additions to both chiral and achiral acceptors. Chapter 3 describes an attempt to synthesize lignans via tandem conjugate additions to a chiral crotonate ester. The project was, however, unsuccessful, due to problems associated with the synthesis of the chiral ester. A number of protected derivatives of ethyl 4-hydroxycrotonate were, however synthesized, as were various mono-protected derivatives of (Z)-1,4-dihydroxybut-2-ene. Chapter 4 describes the synthesis of lignans via tandem conjugate addition to chiral (-)-5-(1-menthyloxy)furan-2(5H)-one. Conjugate addition utilizing diphenyl thioacetals as acyl anion equivalents, followed by in situ trapping with aromatic aldehydes or acid chlorides afforded the adducts in good yields. Desulphurisation and dementhylation yielded (-)-epipodorhizol, which on oxidation afforded (-)-podorhizon. This was successfully cyclised to (-)-γ-apopicropodophyllin, thereby constituting a formal total synthesis of chiral deoxypodophyllotoxin. Chapter 5 describes the use of O-tert-butyldimethysilyl protected cyanohydrins as acyl anion equivalents in the conjugate addition to the chiral butenolide. It has been shown that conjugate additions proceed to afford a single isomer, while tandem conjugate additions afford the adduct as a mixture of two isomers. Ketone regeneration from the cyanohydrin causes isomerisation to occur, to afford a single isomer. A novel dementhylation reaction utilizing sodium borohydride, which occurs with concurrent stereoselective reduction of ther benzylic ketone, is discussed. This methodology has realised the chiral synthesis of a member of the retrolignan series, and the potential for the synthesis of chiral 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.639120  DOI: Not available
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