The synthesis of pyrrolizidine alkaloids

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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
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Neuenschwander, Kent William, "The synthesis of pyrrolizidine alkaloids " (1982).Retrospective Theses and Dissertations. 7468.
https://lib.dr.iastate.edu/rtd/7468
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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