The synthesis of pyrrolizidine alkaloids PDF
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Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1982 The synthesis of pyrrolizidine alkaloids Kent William Neuenschwander Iowa State University Follow this and additional works at:https://lib.dr.iastate.edu/rtd Part of theOrganic Chemistry Commons Recommended Citation Neuenschwander, Kent William, "The synthesis of pyrrolizidine alkaloids " (1982).Retrospective Theses and Dissertations. 7468. https://lib.dr.iastate.edu/rtd/7468 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please [email protected]. INFORMATION TO USERS This was produced from a copy of a document sent to us for microfilming. 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Some pages in any document may have indistinct print, in aii cases we have filmed the best available copy. University Microfilms international 300 N. 7EEB RD , ANN ARBOR. Ml 18106 8221213 Neuenschwander, Kent William THE SYNTHESIS OF PYRROLIZIDINE ALKALOIDS Iowa State University PH.D. 1982 University Microfilms I nt6rn&tiOn al 300 N. zeeb Road. Aim Aibor.MI 48106 The synthesis of pyrrolizidine alkaloids by Kent William Neuenschwander A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Department: Chemistry Major; Organic Chemistry Aooroved: Signature was redacted for privacy. In Cixarg'é of Major work Signature was redacted for privacy. Foir^the Major/Depàift^tèrl't Signature was redacted for privacy. For the Graduate College Iowa State University Ames, Iowa 1982 ii TABLE OF CONTENTS Page INTRODUCTION 1 HISTORICAL 2 RESULTS AND DISCUSSION 29 CONCLUSION 48 EXPERIMENTAL 49 REFERENCES 76 ACKNOWLEDGEMENTS 81 1 INTRODUCTION The pyrrolizidine alkaloids have attracted consider able attention over the last several decades due to their widespread occurrence and interesting range of biological effects. A number of the naturally occurring alkaloids are hepatotoxic and carcinogenic, but some derivatives have potentially useful physiological properties. These include anesthetic and antiviral activities. A wide range of pharmaceuticals, including anti-inflammatory drugs, have been prepared. Some of the quaternary pyrrolizidine salts are powerful parasiticides. This manuscript will detail the results of a program to use the amidoalkylation reaction in the synthesis of some pyrrolizidine alkaloids. HISTORICAL The pyrrolizidine alkaloids constitute an exceptionally large class of naturally occurring compounds found in various families of Compositae, Boraginaceae, Leguminosae, Santa- laceae, and Gramineae (1-6). Although the title pyrrolizidine alkaloids is the most descriptive, frequently members of this group have been designated as Senecio alkaloids derived from the fact that various alkaloids of this group were first discovered in the generea Senecio of the family Compositae. This practice appears to be losing support, however. There are approximately 125 pyrrolizidine alkaloids of known structure. All contain the methyl pyrrolizidine nucleus ^ as the distinguishing skeletal feature. The pyrrolizidine nucleus itself (the necine) possesses one or more hydroxyl groups esterified by organic acids (the necic acids), e.g., Dicrotatine (2). 3 The structures of a number of representative necines are shown in Figure 1. The alkaloids fall into three main categories: monoesters of the necine with a monocarboxylic c6 -OH p C D (±)isoretronecanol (±)trachelanthamidine (±)supinidine HO OH N platynecine hastanecine 6 7. turniforcidine dihvdroxvheliotridane 8. '9 OH FO H ^OH lOH N macronecine rosmarxnecine 10 11 HO „ .OH heliotridine retronecine 12 13 Figure 1. Structures of representative necines
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