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An unambiguous nomenclature for the acylquinic acids commonly known as chlorogenic acids László Abrankó, and Michael N. Clifford J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b00729 • Publication Date (Web): 18 Apr 2017 Downloaded from http://pubs.acs.org on May 1, 2017

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Journal of Agricultural and Food Chemistry

An unambiguous nomenclature for the acyl-quinic acids commonly known as chlorogenic acids László Abrankó† and Michael N. Cliﬀord*§

†László Abrankó Faculty of Food Science, Department of Applied Chemistry Szent István University, 1118 Budapest, Hungary

§ Michael N. Clifford School of Bioscience and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK *Author too whom correspondence should be addressed [email protected]

Key words: Chlorogenic acids, Nomenclature, Quinic acids,

ACS Paragon Plus Environment


Suggested referees Dr Adriana Farah Universidade Federal do Rio de Janeiro, Brazil [email protected] Professor Christian Zidorn University of Kiel, Germany [email protected] Professor Paula Castilho University of Madeira Portugal [email protected] Dr Pedro Mena University of Parma Italy [email protected] Dr Simona Piccolella Second University of Naples


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Department of Environmental, Biological and Pharmaceutical Sciences and Technologies Caserta, Campania, Italy [email protected]



Table of Contents TOC ART

dica ciniuQ Quinic acid

?

dica ciniuQ


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1

Abstract

2

The history of the acyl-quinic acids is briefly reviewed, the merits and limitations of the

3

various nomenclature systems applicable critically compared, and their limitations

4

highlighted, in particular their inability to provide an unambiguous description of all quinic

5

acid

6

Recommendations are made for a nomenclature system which in combination with IUPAC

7

numbering achieves this objective. A comprehensive set of structures for the quinic acid

8

enantiomers and diastereo-isomers is presented. The supplementary information provides

9

an explanation of trivial names and a decision tree to determine which quinic acid isomer a

10

enantiomers

and

diastereo-isomers

and

associated

structure represents.

11


acyl-quinic

acids.

Page 7 of 31


12

Introduction

13

Quinic acid was first reported in 1790,1 but the first acyl-quinic acid was not characterised

14

until 1932 when Fischer and Dangschat proposed that a substance isolated from green

15

coffee beans was 3-O-caffeoylquinic acid (3-CQA).2

16

described by Payen as ‘chlorogen acid’,3, 4 leading to the trivial name ‘chlorogenic acid’. In

17

1950 Barnes et al.5 reported the presence in coffee of the isomer 5-O-caffeoylquinic acid (5-

18

CQA) to which they gave the trivial name neochlorogenic acid

19

structure assignments have stood the test of time, the numbering system applied to the

20

quinic acid moiety was revised by IUPAC in the 1976 recommendations for the numbering of

21

the carbon atoms of cyclitols.6

22

becomes 5-CQA IUPAC, and Barnes et al’s 5-CQA becomes 3-CQA IUPAC,2, 6 (Figure 1).

This substance in 1846 had been

Although both these

In the IUPAC system, Fischer and Dangschat’s 3-CQA

23

Figure 1 here

24

Use is also made of the Cahn–Ingold–Prelog (CIP) sequence rules, but the structure

25

designation obtained depends on whether the 1964 rules,7 or 1966 revision,8 is used. The

26

orientation of substituents in quinic acid can be described also by comparing their

27

orientation relative to that of the C1-COOH, but as pointed out by Eliel and Ramirez,1 one

28

system uses α to describe a substituent trans to the carboxyl, and another uses α to

29

describe a substituent cis to the carboxyl.

30

Both systems of numbering, both sets of CIP rules, and both α,β systems remain in use,

31

sometimes with different approaches used in conjunction, creating confusion which is worse

32

confounded when structures are drawn without regard to the three dimensional nature of

33

the quinic acid moiety, or that three dimensional structure is misrepresented, as highlighted

34

by Kremr et al.9 A review of the botanical distribution of acyl-quinic acids and close allies

35

(e.g. acyl-alkyl quinates, acyl-quinic acid glycosides) confirmed Kremr et al’s observations



36

and located a significant number of publications with incorrect structures and even some

37

publications that used both IUPAC and non-IUPAC numbering interchangeably.10, 11 Similar

38

errors were found in supplier’s on-line catalogues and on-line databases, all further

39

exacerbated by inconsistent use of trivial names.12, 13

40

This perspective examines the various systems employed to describe free quinic acids and

41

acyl-quinic acids and seeks to identify the minimum information required to define their

42

structure unambiguously.

43 44

Quinic acid enantiomers and diastereo-isomers

45

The simple term ‘quinic acid’ term encompasses two pairs of optically active enantiomers

46

((±)-quinic acid (1–2) and (±)-epi-quinic acid (3–4)) and four diastereo-isomers, optically

47

inactive meso forms (muco-quinic 5, cis-quinic 6, neo-quinic 7 and scyllo-quinic 8) (Table 1).

48

1L-(–)-Quinic acid 1 is the only isomer commercially available (although frequently described

49

in catalogues as D-quinic acid rather than L-quinic acid) and generally assumed to be the

50

isomer present in the majority of reported acyl-quinic acids, but only rarely has this been

51

proven.14-18 At least one acyl-(±)-epi-quinic acid has been reported (originally as isoquinic

52

acid), and the quinic acid moiety released by saponification shown to be distinct from 1L-(–)-

53

quinic acid.16

54

fragmentation data that acyl derivatives of a quinic acid isomer, as yet incompletely

55

characterised, occur in several species.21-23 Roasted coffee beans contain a 3-caffeoyl-muco-

56

quinic acid and a 3-feruloyl-muco-quinic acid,24, 25 along with free muco-quinic, free scyllo-

57

quinic and free (±)-epi-quinic acid,26 all of which have been confirmed by synthesis.

58

A recent survey located in excess of 300 closely related mono-, di-, tri- and tetra-acyl-quinic

59

acids and a comprehensive listing thereof and their botanical distribution is available on

19 20

There are reports arising from distinctive retention time and LC–MSn


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60

Researchgate,11, 13 and will not be repeated here. Note, however, that in addition to the

61

well-known trans-cinnamic acids, the acyl moiety might be a dihydrocinnamic acid which

62

may have a side chain hydroxyl or methoxyl substituent, a phenylacetic acid, a benzoic acid

63

or an aliphatic or hydroxy-aliphatic acid, any one of which might occur alone or in numerous

64

permutations. Any nomenclature system must cope unambiguously and conveniently with

65

all of these variations.

66 67

1. The IUPAC system

68

In 1976 IUPAC published their views on how best to define the configuration of cyclitols,

69

cycloalkanes with one hydroxyl on each of at least three ring carbons. Special procedures

70

were required because cyclitols possess features of relative and absolute configuration that

71

are not clearly displayed by general methods of stereochemical nomenclature. IUPAC

72

recognised that the CIP sequence rule system for absolute stereochemistry could be used,

73

but that the sequence rule procedure was complex in this application, a view also held by

74

Corse and Lundin.27 IUPAC considered the Maquenne fractional system, the Posternak

75

system, the Fletcher, Anderson and Lardy system, and the Angyal and Gilman system, but

76

recommended the adoption of the McCasland fractional system with prefixes.

77

Accordingly, IUPAC recommended inter alia that the most common naturally occurring

78

quinic acid should be described as 1L-1(OH),3,4/5-tetrahydroxy-cyclohexanecarboxylic acid

79

with the trivial names (–)-quinic acid or L-quinic acid.6 For quinic acids, according to IUPAC

80

recommendations, the lowest numbered carbon (i.e. C1) is applied to the substituent ‘other

81

than an unmodified hydroxyl group’.

82

recommendations to a pair of enantiomers, e.g. (+)-quinic acid and (–)-quinic acid or (+)-epi-

Note that the application of the IUPAC



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83

quinic acid and (–)-epi-quinic acid, results in one enantiomer being numbered clockwise and

84

the other being numbered anticlockwise (Figure 2a).

85

Figure 2 here

86

As discussed by Corse and Lundin,27 clockwise and anticlockwise numbering can make

87

certain tasks extremely difficult, and in discussions of routes of chemical synthesis they

88

preferred to use the Maquenne fractional system to avoid this complication. However, the

89

Maquenne system uses non-IUPAC numbering, but does permit a convenient distinction

90

between (–)-quinic acid, which is (–)-(3/145) tetrahydroxy-cyclohexane carboxylic acid, and

91

(+)-quinic acid, which is the (+)-(5/134) isomer, with the fraction indicating which hydroxyls

92

are cis to the carboxyl (drawn above the plane of the cyclohexane ring) and which are trans.

93

For the absolute configuration IUPAC stated that a Fischer–Tollens projection should be

94

used with C1 at the top and C2 and C3 at the front edge of the ring (Figure 2b). The

95

configuration is

96

projects to the left. The prefix

97

compound name. A numeral may precede the prefix to identify the defining centre of

98

chirality. Omission of a prefix, or the use of the prefix DL, identifies a meso form.

99

However, it has since become apparent that the IUPAC system applied to quinic acid

D

if the lowest numbered chiral centre projects to the right, and D

L

if it

or L, followed by a hyphen, is itself followed by the

100

derivatives is not without its problems, with some basic IUPAC priority rules being flouted.

101

If one considers, for example, a 3,5-disubstituted formyl-acetylquinic acid, the acetyl group

102

has higher priority than the formyl group. Hence, two obviously very different compounds

103

would have the same recommended name, 3-O-acetyl-5-O-formyl-quinic acid (Figure 2c).

104

Nomenclature software will always suggest this numbering. To avoid this problem the

105

original numbering of the quinic acid parent compound must be maintained in all quinic acid


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106

derivatives, in this case yielding 3-O-acetyl-5-O-formyl-quinic acid and 3-O-formyl-5-O-

107

acetyl-quinic acid.

108 109

2. Use of α and β to designate the orientation of substituents cis and trans to the quinic

110

acid carboxyl

111

The complications inherent in defining the configuration of quinic acid were addressed again

112

in 1997 by Eliel and Ramirez,1 who drew attention to inconsistencies in reference

113

compendia. The configuration of (–)-quinic acid can be defined by the use of the α,β system

114

designed to denote the configuration of the hydroxyl substituents relative to the carboxyl.

115

If substituents trans to the carboxyl are designated α, and those cis are designated β, then

116

(–)-quinic acid is either 1α,3α,4α,5β or 1α,3β,4α,5α depending on which way the ring

117

carbons are numbered. They pointed out that Dictionary of Organic Compounds (6th edition

118

1966) specifies that the cis hydroxyl is on C3, consistent with Beilsteins Handbuch der

119

Organischen Chemie (3rd supplement 1971 and 4th supplement 1983), thus favouring

120

1α,3β,4α,5α. Unfortunately, Chemical Abstracts uses 1α,3α,4α,5β, and this is perpetuated

121

by the RSC’s Chemspider.28

122

Fortunately, because the hydroxyl at C1 must be trans to the carboxyl in any quinic acid or

123

acyl-quinic acid it is possible to deduce which α,β system is being used even if it is not stated

124

explicitly, but this remains a potential source of confusion.

125 126

3. The CIP sequence rules

127

The second problem to which Eliel and Ramirez 1 drew attention arises from the use of the

128

CIP sequence rules — specifically that incorrect configurational descriptors were applied to



129

C1 and C4 of (–)-quinic acid in several reference compendia.1 While Eliel and Ramirez

130

concur that using the CIP sequence rules establishes the C3 and C5 configuration as R, they

131

point out that neither C1 nor C4 are centres of chirality because two of the branches

132

attached to these atoms are identical (–CHOH for C4 and –CH2 for C1). Accordingly C1 and

133

C4 cannot be assigned an R or S priority under the CIP sequence rules as published in 1964.7

134

Never the less, in a footnote to this paper, Eliel and Ramirez following discussion with the Dr

135

J.E. Blackwood, editor of Chemical Abstracts, modify their opinion. They accept that (–)-

136

quinic acid, (+)-quinic acid, (–)-epi-quinic acid and (+)-epi-quinic acid all differ in their

137

descriptors at C1 and C4 if the sequence rule seqcis>seqtrans (i.e. as though the cis

138

substituent had a larger atomic number than the trans substituent), as later proposed by

139

Cahn et al.,8 is utilised, amply illustrating IUPAC’s opinion that the CIP system is complex in

140

this particular application. However, the comment by Blackwood notwithstanding, Eliel and

141

Ramirez recommended that (–)-quinic acid should be defined as 1α,3R,4α,5R-

142

tetrahydroxycyclohexane carboxylic acid, i.e. with α defining a trans substituent.

143

If the rule seqcis>seqtrans as introduced in 1966

144

clearly S and C1 is R because –CH2–CHOH with cis OH at C3 IUPAC is deemed larger than the

145

–CH2–CHOH with trans OH at C5 IUPAC. Accordingly (–)-quinic acid becomes 1R,3R,4S,5R,

146

and fortuitously this designation is valid for both IUPAC and non-IUPAC numbering.

147

Although use of the seqcis>seqtrans rule apparently resolves the problem associated with

148

the CIP descriptors for C1 and C4 of (–)-quinic acid it produces another when muco-quinic or

149

cis-quinic acid are considered. Inversion at C3 (muco-quinic acid) or C5 (cis-quinic acid)

150

produces isomers where C4 has two identical substituents (i.e. either both are cis or both

151

trans), and this is maintained if the substituents are extended further (i.e. to C2 and C6

8

is applied to (–)-quinic acid, then C4 is

1

Note that the structures in the electronic version of this paper must be viewed at high magnification in order to visualise clearly the subtle differences in configuration.


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152

which are both methylenes), and further extension brings C1 into play for each of these

153

substituents. The analogous situation occurs with neo-quinic acid (inverted at C3 and C4)

154

and scyllo-quinic acid (inverted at C4 and C5).

155

However, in these four compounds, C3 and C5 never have the same CIP designation, i.e. one

156

is R and the other is S. Accordingly, this complication can be accommodated only by

157

invoking the rule that ‘a ligand with the descriptor R has priority over its enantiomorph with

158

the descriptor S’.8

159

Inversion only at C4 (i.e. (–)-epi-quinic acid) reverses the cis and trans substituents relative

160

to C4 in (–)-quinic acid but because the position from which the substituents are observed

161

also changes, the nett result is no change and (–)-epi-quinic acid has the same CIP

162

description as (–)-quinic acid, creating another complication, because there does not seem

163

to be a CIP rule to distinguish between the two (+)-quinic acids or the two (–)-quinic acids.

164

Corse and Lundin also noted this anomaly and circumvented it by incorporating the

165

Maquenne fractional formula into the name, thus describing (–)-quinic acid as

166

‘(1R;3R:4S;5R)-3/1,4,5-tetrahydroxycyclohexane-1-carboxylic acid’2 and then stated ‘(–)-epi-

167

quinic acid is probably (1R;3R:4S;5R)-3,4/1,5-tetrahydroxycyclohexane-1-carboxylic acid’,27

168

but, unfortunately using non-IUPAC numbering. With IUPAC numbering (–)-quinic acid

169

becomes (1R,3R,4S,5R)-5/1,3,4-tetrahydroxycyclohexane-1-carboxylic acid and (–)-epi-

170

quinic acid is (1R,3R,4S,5R)-4,5/1,3-tetrahydroxycyclohexane-1-carboxylic acid in the

171

combined CIP–Maquenne designation.

172

Similarly, inversion only at C1 of (–)-quinic acid or (+)-quinic acid produces (–)-epi-quinic acid

173

or (+)-epi-quinic acid, respectively, again with the nett result of no change in the CIP

174

descriptors. However, this introduces another problem because it is the orientation of the 2

Note that there is a typographical error in the paper by Corse and Lundin with the carboxyl of (–)-quinic acid described as at C3 rather than C1 as correctly given by them for (–)-epi-quinic acid.



175

C1-OH that is used in the 1976 IUPAC rule to distinguish L-enantiomers from D-enantiomers,

176

i.e.

177

“…when the formula is drawn in a way that the substituent (i.e. OH group) on the

178

lowest numbered asymmetric carbon atom is above the plane of the ring, and the

179

numbering is clockwise, the compound is L; if anti-clockwise, it is D”.

180

Possibly IUPAC intended this rule to be applied only when the C1-OH was above the plane of

181

the ring, but simply flipping the C1-inverted structure places the C1-OH above the plane of

182

the ring, albeit at the bottom of the structure rather than at the top, and applying the rule

183

quoted above suggests that there has been a change from the L-enantiomer to the D-

184

enantiomer.

185

descriptors and this as noted above has not occurred.

This is incorrect, because such a change requires inversion of all CIP

186 187

Conclusions regarding the adequacy of the CIP rules and other nomenclature systems

188

We conclude that none of the existing systems provide an unambiguous description that can

189

be applied to the eight quinic acids and their acyl derivatives. Our reasoning is set out

190

below:

191

1) In the case of the optically active quinic acids, merely defining the cis / trans

192

orientation of the hydroxyls relative to the carboxyl is insufficient to distinguish

193

between 1L-(–)-quinic acid (1) and 1D-(+)-quinic acid (2) or 1L-(–)-epi-quinic acid (3),

194

and 1D-(+)-epi-quinic acid (4) because both enantiomers are identical (1α, 3α, 4α, 5β

195

and 1α, 3α, 4β, 5β, respectively) if IUPAC numbering is applied.

196

To enable these enantiomers to be distinguished it is necessary to apply the CIP

197

descriptors to the meta-hydroxyls (i.e C3 and C5) which in the case of 1L-(–)-

198

enantiomers are both R and in the case of 1D-(+)-enantiomers are both S.


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199


2) In the case of meso forms (muco-quinic acid (5), cis-quinic acid (6), neo-quinic acid (7)

200

and scyllo-quinic acid (8)) the indication of the cis/trans orientations of the OH

201

groups relative to the COOH group is sufficient to distinguish between all species of

202

free acids, but not if these meso-acids are asymmetrically substituted because this

203

creates new R / S enantiomers.

204

For the avoidance of doubt the asymmetrical derivatives would include, for example, 3-acyl

205

and 5-acyl-meso-quinic acids, and 3,5-diacyl derivatives where two different acyl residues

206

are present, e.g. 3-caffeoyl-5-feruloyl-meso-quinic acid and 3-feruloyl-5-caffeoyl-meso-

207

quinic acid.

208

If such asymmetric acyl-meso-quinic acids derivatives were synthesized from 1L-(–)-quinic

209

acid the acyl-meso-quinic acid would be named as if it had a negative rotation, but if

210

synthesized from 1D-(+)-quinic acid would be named as if it had a positive rotation, because

211

the position of acylation would be defined by the 1976 IUPAC rule applied to the precursor:

212

“…when the formula is drawn in a way that the substituent (i.e. OH group) on the

213

lowest numbered asymmetric carbon atom is above the plane of the ring, and the

214

numbering is clockwise, the compound is L; if anti-clockwise, it is D”.

215

Figure 3 demonstrates the marked and confusing influence on perceived structure of two

216

pairs of asymmetrically substituted acyl-meso-quinic acids associated with which

217

enantiomer was chosen as their synthetic precursor. This is exactly the problem

218

encountered and discussed by Corse and Lundin.27.

219

Figure 3 here

220

Accordingly, a convention must be defined so that a meso-quinic acid, whether or not it is

221

substituted, is numbered independently of its actual or perceived precursor. Corse and



222

Lundin favoured the Maquenne system, but that uses non-IUPAC numbering and therefore

223

we suggest:

224 225

“Clockwise numbering should be used for meso forms, with the formula drawn in such

226

a way that the OH group at C1 is above the plane of the ring”.

227 228

Adoption of this convention then permits distinct and unambiguous descriptions for all eight

229

quinic acids and their acyl derivatives, as presented below:

230 231

(±)-Quinic acid and (±)-epi-quinic acid

232

The minimum requirement for unambiguous description of (±)-quinic acid and (±)-epi-quinic

233

acid and their acyl derivatives is the use of IUPAC numbering, and:

234

a)

1L-(–)-quinic acid

3R, 5R-(1α, 3α, 4α, 5β)

235

b)

1D-(+)-quinic acid

3S, 5S-(1α, 3α, 4α, 5β)

236

c)

1L-(–)-epi-quinic acid

3R, 5R-(1α, 3α, 4β, 5β)

237

d)

1D-(+)-epi-quinic acid

3S, 5S-(1α, 3α, 4β, 5β)

238 239

Meso-quinic acids

240

The minimum requirement for unambiguous description of the meso-quinic acids, including

241

the asymmetric acyl-meso-quinic acids is the use of IUPAC numbering and the convention

242

given above, yielding:

243

a)

muco-quinic acid

3S, 5R (1α, 3β, 4α, 5β)

244

b)

cis-quinic acid

3R, 5S (1α, 3α, 4α, 5α)

245

c)

neo-quinic acid

3S, 5R (1α, 3β, 4β, 5β)


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246


d)

scyllo-quinic acid

3R, 5S (1α, 3α, 4β, 5α)

247 248

Guidelines for presenting the structure of these various acyl-quinic acids.

249

It is not easy to convert the descriptions listed above into the associated structures.

250

Moreover, such three dimensional structures are not easily presented on a plane surface, in

251

part because a subtle change in perspective generates structures for a single compound that

252

appear very different to the untrained eye. Accordingly, Table 1 presents for all eight quinic

253

acid isomers the relevant CIP description, the proposed unambiguous description, the

254

Fischer–Tollens structure, both ideal chair conformations, and the two-dimensional

255

structure as viewed from four different perspectives.

256

These different perspectives are ‘from in front’, ‘from behind’, from the left’ and ‘from the

257

right’, these latter necessary because in these structures the carboxyl and hydroxyl at C1 are

258

projecting at right angles to the plane of the medium on which they are presented — the

259

substituent with the hatched bond is projected into the medium and away from the

260

observer and the substituent with the solid bond is projected out of the medium and

261

towards the observer. If the observer is looking straight down the C–C bond of the carboxyl,

262

or the C–O of the hydroxyl, as appropriate, then the other substituent projecting into the

263

medium would be masked by the substituent projecting out of it.

264

Accordingly, the structures have to be presented with the observer looking at an angle

265

either slightly less than 90° (i.e. from the left) or slightly more than 90° (i.e. from the right) in

266

order to see both C1 substituents. Depending on which of these positions is adopted by the

267

observer the carboxyl will either appear to the left and the hydroxyl to the right, or the

268

carboxyl to the right and the hydroxyl to the left, but it is the same compound. This is



Page 18 of 31

269

possibly the most confusing feature associated with presenting three dimensional structures

270

in two dimensions.

271

It is hoped that the nomenclature system proposed here, used in combination with the

272

structures in Table 1 will ensure that free quinic acids and acyl-quinic acids are

273

unambiguously described and correctly presented. Two further problems remain. In the

274

introduction attention was drawn to publications in which IUPAC and non-IUPAC numbering

275

were used simultaneously and without qualification, with, for example, data reported in one

276

paper for 3-CQA non-IUPAC being discussed unwittingly with data from another paper for 3-

277

CQA IUPAC, resulting in unreliable conclusions as discussed elsewhere.10

278

unacceptable and it is essential that only one system is used, preferably IUPAC, and a brief

279

statement to this effect is desirable. To ensure consistency, suppliers’ descriptions of

280

commercial standards, and data from previous publications, should if necessary be

281

amended to the IUPAC numbering system and a clear statement made to this effect. If it is

282

not possible to define which system has been used in a previous publication then this should

283

be clearly noted when discussing that data along with a statement that the numbering and

284

name have been left unchanged.

285

Trivial nomenclature can be found in the literature with IUPAC and non-IUPAC numbering,

286

and there are other complications, for example, the term ‘isochlorogenic acid a’ does not

287

correspond to the term ‘isochlorogenic acid A’.29, 30 A comprehensive referenced listing of

288

trivial names with their IUPAC equivalent is provided as Supplementary Table 1.

289

The correct and unambiguous description of natural products is essential especially when

290

significant properties or attributes are claimed for one particular isomer.

291


This is

Page 19 of 31

292


References References

293 294 295

1.

296

Tetrahedron: Asymmetry 1997, 8, 3551-3554.

297

2.

298

Chinasäure und Derivate). Berichte 1932, 65, 1037-1040.

299

3.

Payen, Untersuchung des Kaffees. Annalen 1846, 60, 286-294.

300

4.

Payen, Memoire sur le café (3o Part). Comptes Rendus 1846, 23, 244-251.

301

5.

Barnes, H. M.; Feldman, J. R.; White, W. V., Isochlorogenic acid isolation from coffee and

302

structure studies. J. Am. Chem. Soc. 1950, 72, 4178-4182.

303

6.

IUPAC, Nomenclature of cyclitols. Biochem. J. 1976, 153, 23-31.

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7.

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375



376

Figure 1 Non-IUPAC

IUPAC 1976

377 378

Figure 1. IUPAC and non-IUPAC numbering of 1L-1(OH),3,4/5-tetrahydroxy-cyclohexanecarboxylic

379

acid [1L-(–)-quinic acid].

380 381


Page 24 of 31

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382 1L-(-)-Quinic acid (IUPAC)

1D-(+)-Quinic acid (IUPAC)

clockwise

anti-clockwise

A

B

Fisher-Tollens projections H O

C

HOOC 1 OH

O

4

5 3 O

OH CH3

O

383 384 385

Figure 2. Selected structures to illustrate the conflicts and complexity of presenting quinic acid

386

enantiomers and associated acyl-quinic acids when using IUPAC recommendations

387

2A. IUPAC recommendations for clockwise and anti-clockwise numbering of enantiomers

388

2B. Fischer–Tollens projections for 1L-(–)-quinic acid and 1D-(+)-quinic acid

389

2C. Two conflicting structures that strict application of IUPAC rules designate as 3-O-acetyl-5-O-

390

formyl-(–)-quinic acid

391



3-Acyl derivative prepared

3-Acyl derivative prepared

from 1L-(–)-quinic acid

from 1D-(+)-quinic acid

3,5-Di-acyl derivative

3,5-Diacyl derivative

prepared from 1L-(–)-quinic

prepared from 1D-(+)-

acid

quinic acid

392 393

394 395 396

Figure 3 Conflicting structures obtained if IUPAC rules are applied to asymmetrically

397

substituted meso-quinic acid enantiomers prepared from 1L-(–)-quinic acid and 1D-(+)-quinic

398

acid

399


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Table 1 An unambiguous nomenclature for the acyl-quinic acids commonly known as chlorogenic acids

Isomer

1. 1L-(–)quinic acid

CIP description and recommended description 1R, 3R, 4S, 5R or 3R, 5R-(1α, 3α, 4α, 5β)

Fischer–Tollens Structure

2D structure using the recommended convention

Conformers

2D structures for individual isomers drawn from four different perspectives

HOOC

1R

OH 5R OH

3R HO (Top one with equatorial COOH and axial 4H is shown in 26 Corse and Lundin 1970. Carboxy 26 equatorial preferred.

OH 4S

1S, 3S, 4R, 5S or 3S, 5S-(1α, 3α, 4α, 5β)

HOOC

5R OH

1S

OH 3S OH

OH 4R HO

1S

1R HOOC OH 5R HO

3S OH OH 4R

HO

3R OH

1S

COOH 5S OH

3S HO 180 deg

COOH

5S HO


3R OH

OH 4S

5S HO (Top one with equatorial COOH and axial 4H is shown in 26 Corse and Lundin 1970). Carboxy 26 equatorial preferred.

COOH

5R HO

OH 4S 2. 1D-(+)quinic acid

1R

OH 180 deg 4S

HO 1R COOH 3R HO

HO

OH 4R

1S HOOC OH 3S HO

5S OH OH 4R


3. 1L-(–)-epiquinic acid (derived from 1L-(–)quinic acid by 4-OH inversion)

1R, 3R, 4S, 5R or 3R, 5R-(1α, 3α, 4β, 5β)

4. 1D-(+)epi-quinic acid (derived from 1D-(+)quinic acid by 4-OH inversion)

1S, 3S, 4R, 5S or 3S, 5S-(1α, 3α, 4β, 5β)

(Top one with axial COOH and 4H is suggested by Corse and Lundin 26 1970). Carboxy axial 26 preferred.

or

Carboxy axial preferred.26


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5. Mucoquinic acid (derived from 1L-(–)quinic acid by 3-OH inversion) meso form


1S, 3S, 4R, 5R or 3S, 5R (1α, 3β, 4α, 5β)

HOOC

1S

OH

3 or 5S HO

5 or 3R OH OH 4R

or

HO

1S

COOH R OH

6. Cis-quinic acid (derived from 1L-(–)quinic acid by 5-OH inversion) meso form

1S

COOH S OH

R HO 180 deg

S HO Carboxy equatorial preferred.26

HO

OH

HOOC

1S

OH

R HO

S OH OH

OH

1R, 3R, 4S, 5S or 3R, 5S (1α, 3α, 4α, 5α)

OH 2 1 COOH OH 6 3 OH OH 5

or

4

Carboxy axial preferred.26

7. Neoquinic acid (derived from 1L-(–)quinic acid by 3-OH and 4-OH inversion) meso form

1S, 3S, 4S, 5R or 3S, 5R (1α, 3β, 4β, 5β)

HOOC

1S

OH

3 or 5S HO

5 or 3R OH OH 4S

or

HO 1S COOH R OH

S HO Carboxy axial preferred.


26

OH 4S

HO

1S

COOH S OH

R HO

OH 180 deg 4S 1S HOOC OH R HO

S OH OH 4S


8. scylloquinic acid (derived from 1L-(–)quinic acid by 4-OH and 5-OH inversion) meso form

Page 30 of 31

1R, 3R, 4R, 5S or 3R, 5S (1α, 3α, 4β, 5α)

or

Carboxy equatorial preferred.


26

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