Thesis-Final 03 June 2011 pdf - Jacobs University

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Abstract The chlorogenic acids are a family of esters formed between certain trans-cinnamic acids and quinic acid. Chlorogenic acids are among the most abundant polyphenols, which are naturally occurring in plants, with various biological activities beneficial to human health. Chlorogenic acids are secondary metabolites that are found in plants. As a group they generally contain several subgroups and usually several isomers within each subgroup. The development of methods for the synthesis of existing chlorogenic acids and new series of chlorogenic acids were developed in this thesis in order to have the compounds available as analytical standards, for confirmation of previous and future LC/MS work, and most importantly for individual biological testing in various assays. The target compounds were obtained with two strategies 1.selective synthesis using appropriate protecting groups strategies, 2.nonnselective synthesis producing mixtures of isomers. The general strategy, which was applied through out the thesis in order to synthesise the target compounds was, as follows; • Preperation of acid chlorides of cinnamic acids • Preparation of protected quinic acid derivatives • Acylation • Deprotection A series of mono-acyl chlorogenic acids and esters, in particular of those substituted in the 1-, 3-, 4- and 5- positions of the quinic acid with coumaroyl, feruloyl, caffeoyl and dimethoxy cinnamoyl and cinnamoyl substituents, have been successfully synthesised. As intermediates in these syntheses a series of quinide esters, potential metabolites and degradation products of naturally occurring chlorogenic acids have also been obtained. The first examples of di-acyl chlorogenic acids, have been successfully synthesised. A general protection and deprotection strategy for the synthesis of chlorogenic acids has been established. Poly-acyl chlorogenic acids starting from qunic acid and quinic acid lactones also have been established. The right conditions for the synthesis of certain type of chlorogenic acids and esters have been established in this work. i
“Imagination is more important than knowledge” Albert Einstein (1879-1955) ii
Page 1: Synthesis of Chlorogenic Acids & Ch
Page 5 and 6: Abbreviations Ac Ac 2 O AcOH MeCN C
Page 7 and 8: CONTENT Chapter 1 vi
Page 9 and 10: Content Chapter 1 Preparation of ac
Page 11 and 12: Content Chapter 1 (1S, 3R, 4R, 5R)-
Page 13 and 14: Background Chapter 2 Phenolic Phyto
Page 15 and 16: Background Chapter 2 Types of polyp
Page 17 and 18: Background Chapter 2 Stilbenes cont
Page 19 and 20: Background Chapter 2 Biosynthesis o
Page 21 and 22: Background Chapter 2 Biological act
Page 23 and 24: Background Chapter 2 terpenoids, to
Page 25 and 26: Background Chapter 2 Table 2: Bioav
Page 27 and 28: Background Chapter 2 These well kno
Page 29 and 30: Background Chapter 2 Hydroxycinnami
Page 31 and 32: Background Chapter 2 small amounts
Page 33 and 34: Background Chapter 2 Cinnamate tran
Page 35 and 36: Background Chapter 2 used in the is
Page 37 and 38: Background Chapter 2 acid is implic
Page 39 and 40: Background Chapter 2 Chlorogenic ac
Page 41 and 42: Background Chapter 2 HO O HO OH C O
Page 43 and 44: Background Chapter 2 acyl migration
Page 45 and 46: Background Chapter 2 Reported Synth
Page 47 and 48: Background Chapter 2 1-O-Cinnamoylq
Page 49 and 50: Background Chapter 2 O O O H + CinO
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Background Chapter 2 Synthesis of 1
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Background Chapter 2 Esterification
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Background Chapter 2 Synthesis of 3
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Background Chapter 2 Table 5: Chlor
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Background Chapter 2 roasting degre
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Aims and objectives As described ch
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Results and discussion Chapter 3 Pr
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Results and discussion Chapter 3 co
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Results and discussion Chapter 3 1.
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Results and discussion Chapter 3 Qu
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Results and discussion Chapter 3 In
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Results and discussion Chapter 3 CH
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Results and discussion Chapter 3 Al
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Conclusions Chapter 4 Conclusions A
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Conclusions Chapter 4 Mono-acyl chl
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Conclusions Chapter 4 The products
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Conclusions Chapter 4 Di-acyl chlor
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Conclusions Chapter 4 Poly-acyl chl
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EXPERIMENTAL Chapter 5 181
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Synthesis of starting materials Qui
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Annex Chapter 6 Acetyl ferulic acid
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Annex Chapter 6 3, 4-dimethoxycinna
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Annex Chapter 6 3, 4-O-Isopropylide
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Annex Chapter 6 1-(β, β, β-trich
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Annex Chapter 6 (1S, 3R, 4R, 5R)-1-
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Annex Chapter 6 (1R,3R,4S,5R)-1-dim
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Annex Chapter 6 (1R, 3R, 4S, 5R)-1-
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Annex Chapter 6 (1R, 3R, 4S, 5R)-1-
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Annex Chapter 6 5- diacetylcaffeoyl
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Annex Chapter 6 5- acetyl p-coumaro
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Annex Chapter 6 5-cinnamoyl bisacet
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Annex Chapter 6 5-O-feruloylquinic
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Annex Chapter 6 5-O-dimethoxycinnam
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Annex Chapter 6 (1S,3R,4R,5R)-1-(β
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Annex Chapter 6 (1S,3R,4R,5R)-1-(β
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Annex Chapter 6 (1S,3R,4R,5R) 1- (
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Annex Chapter 6 (1S,3R,4R,5R)-3, 4-
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Annex Chapter 6 (1S,3R,4R,5R)-3,4-b
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Annex Chapter 6 (1S,3R,4R,5R)-1,3-d
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Annex Chapter 6 (1S,3R,4R,5R)-1,3-b
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Annex Chapter 6 (1S,3R,4R,5R)-1,4-d
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Annex Chapter 6 Quinide tri-acetate
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Annex Chapter 6 (1S, 3R, 4R, 5R)-1,
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Annex Chapter 6 745 [M+H], 544 [M-C
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Annex Chapter 6 (C-24), 121.95 (C-3
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Annex Chapter 6 (acetylferuloyl) qu
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REFERENCES Chapter 6 253
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References Chapter 6 21 D. Strack,
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References Chapter 6 62 K. Herrmann
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References Chapter 6 104 N. Shibuya
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References Chapter 6 148 B. Möller
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References Chapter 6 187 M. Nardini
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References Chapter 6 221 M. F. Andr
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References Chapter 6 264 L. Panizzi
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References Chapter 6 303 J. Hucke,
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