Synthesis of 13C-labelled ω-hydroxy carboxylic acids of the general formula HO213C-(CH2)n-CH2OH or HO2C-(CH2)n-13CH2OH (n = 12, 16, 20, 28)

Received: 28 April 2021

DOI: 10.1002/jlcr.3931

Revised: 15 June 2021

Accepted: 15 June 2021

R E S E A R C H A R T I C L E

Synthesis of ¹³C-labelled ω-hydroxy carboxylic acids of the

13

general formula HO₂C-(CH₂)_n-CH₂OH or HO₂C-

(CH₂)_n-¹³CH₂OH (n = 12, 16, 20, 28)

Carina Schink¹| Sandra Spielvogel²| Wolfgang Imhof¹

¹Institute of Integrated Natural Sciences,

¹³C-labelled ω-hydroxy-carboxylic acids HO₂¹³C-(CH₂)_n-CH₂OH or HO₂C-

University Koblenz - Landau, Koblenz,

(CH₂)_n-¹³CH₂OH (n = 12, 16, 20, 28) with ¹³C labels selectively introduced

Germany

²Institute of Plant Nutrition and Soil

either at the carboxy group or at the primary alcohol function at the end of the

Science, Christian-Albrechts-University

hydrocarbon chain have been synthesized. Different synthetic strategies had to

Kiel, Kiel, Germany

be applied depending on the position of the label, the chain length of the

respective synthetic target and due to economic considerations. ¹³C labels in

Correspondence

Wolfgang Imhof, Institute of Integrated

general were introduced by nucleophilic substitution of a suitable leaving

Natural Sciences, University Koblenz -

Landau, Universitätsstr. 1, D-57060

group with labelled potassium cyanide and subsequent hydrolysis of the

Koblenz, Germany.

nitriles to produce the corresponding labelled carboxy functions, which may

Email: imhof@uni-koblenz.de

also be reduced to give the labelled primary alcohol group. All new compounds

Funding information

University Koblenz - Landau

are characterized by GC/MS, IR and NMR methods as well as by elemental

analysis.

K E Y W O R D S

¹³C labelling, cutin, fatty acids, suberin, ω-hydroxy-carboxylic acids

1 | INTRODUCTION

additional functional groups in the middle of the hydro-

carbon chain. Chain lengths of 16 or 18 carbon atoms are

most common for the above mentioned constituents of

cutin and suberin although chain lengths up to 26 carbon

atoms have also been observed regularly.^1,13In addition,

there are also significant amounts of aromatic building

blocks like ferulate and in most cases to a lower extend

coumarate, sinapate or caffeate.^14,16–19

In contrast to hydrolysable lipid sources in soil, stud-

ies of microbial transformation of cutin and suberin are

almost absent.^20,21Microbial utilization of specific pre-

cursors, de novo synthesis of individual compounds as

well as transformation and recycling of existing lipids are

known to occur in pure culture systems but have rarely

been investigated in soils.^22–25This is in particular due to

Cutin and suberin are naturally occurring polyesters

being present in plants either in the cuticle or in the roots

acting as the aerial interface between the plant's organs

and the atmosphere or as a barrier between the plant and

the soil environment.^1–11As a consequence of being

described as polyesters, cutin and suberin are composed

of monomeric organic residues containing either alcohol

functions or carboxylic groups.^1,12–15Next to

unsubstituted fatty acids α,ω-dicarboxylic acids,

ω-hydroxy fatty acids, alkane-1-ols and α,ω-alkanediols,

varying amounts of gylcerol are observed in cutin and

suberin. In addition, there are fatty acid derivatives

exhibiting epoxy or one or two hydroxy groups as

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any

medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

J Label Compd Radiopharm. 2021;64:385–402.

wileyonlinelibrary.com/journal/jlcr

385

386

SCHINK ET AL.

the lack of commercially available labelled monomers

that might be used as markers, for example, in ¹³CO₂

arising from the catabolic use of the respective monomers

or for the identification of compounds derived from the

chemical transformation of these compounds. Our

research goal focuses more on the life cycle of these lipid

materials—after they have been produced by the degra-

dation of cutin and suberin—and on their recycling by

soil-based microorganisms. In a preceding paper, we

already presented the synthesis of ¹³C-labelled dicarbox-

ylic acids of the general formula HO₂¹³C-(CH₂)_n-¹³CO₂H

(n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28).²⁶In the present

paper, we will describe strategies for the synthesis of

ω-hydroxy-carboxylic acids HO₂¹³C-(CH₂)_n-CH₂OH or

HO₂C-(CH₂)_n-¹³CH₂OH (n = 12, 16, 20, 28) with ¹³C

labels selectively introduced either at the carboxy group

or at the primary alcohol function at the end of the

hydrocarbon chain.

which would need organometallic catalysts and polar

solvents.^27–29In addition, solid K¹³CN is more easily han-

dled than gaseous reagents, and the exact stoichiometry

also is easily adjusted. This is why K¹³CN has also been

used for the synthesis of labelled calcitroic acid.³⁰Never-

theless, compared with the synthesis of dicarboxylic acids

by the reaction of two equivalents of K¹³CN, it has to be

kept in mind that due to the use of only one equivalent

of K¹³CN for the synthesis of the compounds described in

this contribution, all intermediates before the introduc-

tion of the label have to show an odd number of carbon

atoms.

2.1 | Synthesis of ω-hydroxy carboxylic

acids HO₂¹³C-(CH₂)_n-CH₂OH (n = 12,

16, 20, 28)

Scheme 1 shows the synthetic strategies that led to the

synthesis of ω-hydroxy carboxylic acids HO₂¹³C-(CH₂)_n-

CH₂OH (n = 12, 16, 20, 28), 8a–d, showing the ¹³C label

at the carboxy group. The crucial intermediates were the

ω-bromo-alcohols, 6a–d, in which the carbon chains

already show the desired chain length and which exhibit

two different functional groups in α- and ω-position,

respectively, that allow for the selective transformation of

either of those into the desired functional groups in the

final product.

2 | RESULTS AND DISCUSSION

In a preceding paper describing the synthesis of labelled

dicarboxylic acids, we were able to show that the use of

K¹³CN was the optimal choice to introduce ¹³C by nucle-

ophilic substitution of a suitable leaving group.²⁶This

strategy turned out to be advantageous with respect to

the use of other C₁building blocks as ¹³CO or ¹³CO₂,

SCHEME 1 Synthetic pathway to ω-hydroxy carboxylic acids HO₂¹³C-(CH₂)_n-CH₂OH (n = 12, 16, 20, 28), 8a–d

SCHINK ET AL.

387

The synthesis of 8a representing the product with the

Reaction of the α,ω-diols, 5a–d, with concentrated

hydrobromic acid led to a nucleophilic substitution of

one of the hydroxo groups against a bromine atom and

therefore allowed the isolation of the ω-bromo-alcohols,

6a–d. Nevertheless, it has to be pointed out that the reac-

tion proceeded very slowly with reaction times of up to

72 h and additional portions of hydrobromic acid had

to be added in order to achieve satisfactory yields. Com-

pounds 6a–c were purified by column chromatography

whereas crude 6d precipitated from the reaction mixture

upon the addition of water. The resulting solid was then

recrystallized from a mixture of light petroleum and etha-

nol. The ω-bromo-alcohols were obtained in yields of 71%

(6a), 77% (6b), 69% (6c) and 55% (6d).

shortest carbon chain length may be started from the

corresponding tridecanoic dicarboxylic acid, 1a. In con-

trast to 1a, dicarboxylic acids with 17, 21 or 29 carbon

atoms that would have been needed to synthesize 8b–d

according to the same strategy are either not commer-

cially available or extremely expensive. The

corresponding ω-bromo-alcohols, 6b–d, therefore had to

be synthesized from starting compounds with a lower

number of carbon atoms. Our first idea to elongate

shorter ω-bromo-alcohols protected at the alcohol func-

tion by a Grignard reaction with a suitable α,ω-dibromo-

alkane failed. We therefore treated two equivalents of

commercially available ω-bromo-alkenes with magne-

sium to get the respective Grignard compounds, which

were then coupled with a suitable α,ω-dibromo-alkane in

the presence of lithium tetrachlorocuprate as the catalyst

to produce the α,ω-dienes 4a–c. This means that the reac-

tion of 4-bromo-but-1-ene, 2a, with dibromo-1,9-nonane,

3a, produced 1,16-heptadecadiene, 4a. In analogy,

In the ω-bromo-alcohols, the bromine atom is a much

better leaving group in nucleophilic substitution reac-

tions than the hydroxo group allowing for the selective

substitution of only one of the functional groups. Reac-

tion with cyanide ions in DMSO therefore led to the iso-

lation of ω-hydroxo-nitriles 7a–d. The reaction conditions

were modified compared with a literature procedure of

Jiménez et al.³³Because K¹³CN is quite expensive, we

reduced the amount from three equivalents in the origi-

nal paper to only a slight excess of 1.05 equivalents. Nev-

ertheless, reaction times then had to be drastically

increased from 24 to 72 h, and reaction temperatures had

to be raised from room temperature to 70^ꢀC. In addition,

the reactions had to be monitored by GC/MS in order to

prove that the transformation is complete. The com-

pounds were isolated in excellent yields after chromato-

graphic workup (¹³C-labelled compounds are marked

with an asterisk *: 7a: 95%; 7a*: 96%; 7b: 94%; 7b*: 95%;

7c: 95%; 7c*: 94%; 7d: 94%; 7d*: 95%). Successful labelling

could easily be demonstrated by ¹³C-NMR spectroscopy.

In comparison with the spectrum of the analogous com-

pound of a ¹²C-cyano group, the signal for the carbon

atom of the cyano group at 120.0 ppm is the peak of

highest intensity in the spectrum of the labelled com-

pound. In addition, the signal at 17.2 ppm representing

the methylene group directly attached to the cyano group

is split up to a dublett by carbon–carbon coupling

(¹J_CC= 56.04 Hz). Signals for the next methylene groups

5-bromo-pent-1-ene,

2b,

upon

treatment

with

1,11-dibromo-undecane, 3c, gave heneicosane-1,20-diene,

4b, and the reaction of 9-bromo-non-1-ene, 2c, with

1,11-dibromo-undecane, 3c, allowed the isolation of

nonacosane-1,29-diene, 4c. In order to avoid side prod-

ucts from the reaction of only one equivalent of the

Grignard compound with dibromide, the corresponding

ω-bromo-alkenes, 2a–c, were introduced into the reaction

in a slight excess. Reaction times had to be increased to

18 h as GC/MS measurements after shorter reaction

times showed that there still were side products from

mono-coupling as well as non-reacted dibromide present.

Due to additional contamination with alkenes of unde-

sired chain lengths from transmetallation side reactions,

chromatography became tedious. Small fractions were

taken and analysed, and impure fractions were repurified

a second or even a third time. This procedure led to sam-

ples of 4a–c of high purity and gave combined yields of

71% (4a), 85% (4b) and 77% (4c).

Conversion of the α,ω-dienes, 4a–c, into the

corresponding α,ω-diols, 5b–d, was achieved according to

a procedure published by Drescher et al. by hydro-

boration using disiamylborane, which has to be freshly

prepared immediately before use followed by a workup

with hydrogen peroxide under basic conditions.^31,32This

procedure regioselectively led to the anti-Markovnikov

products in high yields. Compounds 5b (90%) and 5c

(88%) could be purified by column chromatography

whereas 5d (93%) was crystallized from THF. The

shortest α,ω-diol, 5a, could be synthesized by reduction

of the corresponding dicarboxylic acid, 1a, with LiAlH₄

and was isolated in 97% yield after recrystallization from

a heptane/methanol mixture.

2

3

are also split up, although J_CCand J_CCcoupling con-

stants as expected are much smaller (cf. Section 4 and

supporting information). Similar observations can be

1

made in the H-NMR spectra of ¹²C-7a and ¹³C-7a. In

¹²C-7a, the methylene groups directly attached to the

hydroxo group and the cyano group both give tripletts

upon coupling of the homotopic hydrogen atoms with

the two hydrogen atoms of the next methylene group. In

the corresponding spectrum of ¹³C-7a, the signal of the

methylene group next to the hydroxo function still is

observed as a triplett whereas the signal representing the

388

SCHINK ET AL.

methylene group next to the labelled cyano group now is

split up into a complex signal by additional coupling of

the methylene hydrogen atoms with the ¹³C atom of the

cyano group.

the incorporation of the label by K¹³CN followed by a

hydrolytic reaction to produce a labelled carboxy group

and subsequent reduction will lead to the desired labelled

primary alcohol group. Nevertheless, in the target com-

pounds, there is another carboxy group that should

remain non-labelled and that would also be reduced in

the final reaction step. The label therefore had to be

introduced in an early stage of the synthetic procedure

before the non-labelled carboxylic group had to be built

up in an alternative way.

Compounds 2e–h that already show the desired

number of carbon atoms were produced from shorter

ω-bromo-alkenes as the substrates via the route already

depicted in Scheme 1. Nevertheless, in contrast to the

procedure shown before, now an equimolar amount

of the ω-bromo-alkene and the corresponding

α,ω-dibromo-alkane had to be used to still have one

bromine substituent present in the product molecules.

So the reaction of 4-bromo-but-1-ene, 2a, with

1,10-dibromodecane, 3b, produced 14-bromo-tetradec-

1-ene, 2e. If 9-bromo-non-1-ene, 2c, was treated with

1,9-dibromononane, 3a, 19-bromo-nonadec-1-ene, 2f,

was formed. In case of 10-bromo-dec-1-ene, 2d, as the

substrate, the reaction with 1,12-dibromododecane, 3d,

yielded 22-bromo-docos-1-ene, 2g, whereas the reaction

with 1,20-dibromoeicosane, 3e, ended up in the

The target compounds 8a–d were now easily accessi-

ble by hydrolysis of the ω-hydroxo-nitriles, 7a–d, to pro-

duce the corresponding ω-hydroxo carboxylic acids. In

principle, hydrolysis of nitriles might be performed under

basic or acidic conditions. We chose basic conditions

because we expected side reactions of the alcohol func-

tions in the presence of strong acids. In contrast to a simi-

lar reaction reported in the literature, reaction times had

to be drastically increased (up to 24 h instead of 5 h) and

the workup procedures had to be adjusted according to

the significant longer carbon chain lengths.³⁴Instead of

an extractive workup, we added water to the reaction

mixture and adjusted the pH to 1 leading to the precipita-

tion of the crude products. Compounds 8a–d were then

recrystallized from a mixture of ethyl acetate and light

petroleum. Under the reported conditions, the ω-hydroxo

carboxylic acids, 8a–d, are isolated in good yields (8a:

86%; 8a*: 89%; 8b: 88%; 8b*: 91%; 8c: 89%; 8c*: 93%; 8d:

90%; 8d*: 87%).

2.2 | Synthesis of ω-hydroxy carboxylic

acids HO₂C-(CH₂)_n-¹³CH₂OH (n = 12,

16, 20, 28)

formation

of

30-bromo-triacont-1-ene,

2h.

All

α,ω-dibromo-alkanes were commercially available with

the exception of 1,20-dibromoeicosane, 3e, which was

available in two steps from icosanedioc acid via

reduction with LiAlH₄and subsequent bromination

with HBr/Ac₂O.

Scheme 2 shows the synthetic strategies we used to

obtain ω-hydroxy carboxylic acids, 14a–d, with a ¹³C

label at the primary alcohol function. It is obvious that

SCHEME 2 Synthetic pathway to ω-hydroxy carboxylic acids HO₂C-(CH₂)_n-¹³CH₂OH (n = 12, 16, 20, 28), 14a–d

SCHINK ET AL.

389

The ω-bromo-alkenes 2e–h were used as the starting

reaction sequence, obviously, only one of the K¹³CN sam-

ples had the correct purity whereas the others showed

lower purities (cf. supporting information).

compounds to introduce the ¹³C label by nucleophilic sub-

stitution of the bromine substituents against cyano groups.

In analogy to the above mentioned synthesis of 7a–d, the

reaction was performed in DMSO and was monitored by

GC/MS, which led to reaction times of 72 h until the reac-

tion was completed. After extraction of the crude products,

9a–c were purified by column chromatography and 9d by

recrystallization from light petroleum, thus obtaining the

products in good to excellent yields (9a: 91%; 9a*: 88%; 9b:

89%; 9b*: 91%; 9c: 92%; 9c*: 95%; 9d: 84%; 9d*: 89%).

Protection of the carboxy groups in 11a–d was

achieved by esterification with acetic anhydride in pyri-

dine using a bigger excess of acetic anhydride and work-

ing at higher temperatures compared with the published

procedure, thus significantly shortening reaction times.³⁶

The ω-alkenyl acetates 12a–d were purified by column

chromatography and were obtained in high to excellent

yields (12a: 91%; 12a*: 94%; 12b: 97%; 12b*: 94%; 12c:

93%; 12c*: 96%; 12d: 86%; 12d*: 84%).

Hydrolysis of the ω-cyano-alkenes 9a–d was again per-

formed in an ethanolic sodium hydroxide solution due to

the good performance of these conditions in the synthesis

of 8a–d. The crude products were purified by column

chromatography (10a) or by recrystallization from a mix-

ture of ethyl acetate and light petroleum (10b–d). In all

cases, excellent yields of the corresponding ω-alkenyl-

carboxylic acids were realized (10a: 93%; 10a*: 96%; 10b:

90%; 10b*: 93%; 10c: 93%; 10c*: 91%; 10d: 84%; 10d*: 93%).

The intermediates 11a–d were then obtained by

reduction of 10a–d with LiAlH₄, which does not reduce

electron-rich isolated double bonds and was therefore

expected to leave the terminal alkenyl groups unreacted

without having to protect them.³⁵Purification was done

either by column chromatography (11a–c) or by recrys-

tallization from a mixture of ethyl acetate and light petro-

leum (11d). Also in this stage, yields were highly

satisfactory (11a: 93%; 11a*: 90%; 11b: 95%; 11b*: 96%;

11c: 92%; 11c*: 94%; 11d: 84%; 11d*: 92%). In the

¹H-NMR spectra of the ω-alkenyl-alcohols 11a–d, the

most significant signal is related to the methylene group

in which the carbon atom is the ¹³C label. Protons of this

group due to coupling with the two hydrogen atoms of

the next methylene groups are expected to be observed as

a triplett. Because of the additional coupling with the ¹³C

atom in the spectra, a doublet of tripletts is observed

(¹J_CH= 140.9 Hz). Nevertheless, it gets obvious from the

spectra that some of the K¹³CN samples that we used in

the synthesis of a series of the compounds did not have

the purity (99%) that we had expected according to the

specifications of the supplier. Next to the doublet of

tripletts, we in all cases observed a small triplett in the

Oxidative cleavage of the terminal carbon–carbon

double bond leads to the formation of the final carboxyl

group and also reduces the carbon chain length by one

carbon atom (ending up as formic acid). This also is the

reason why all intermediates so far showed one carbon

atom more than the desired number in the final products.

For economical as well as toxicological reasons, we chose

KMnO₄as the oxidative agent although the reaction

would also been possible with RuO₄or OsO₄.^37–39After

extraction, the ω-acetoxy carboxylic acids purified by col-

umn chromatography (13a–c) whereas 13d was filtered

directly from the reaction mixture and was recrystallized

from a mixture of ethyl acetate and light petroleum.

Observed yields were identical or even better than those

reported in the literature (13a: 80%; 13a*: 75%; 13b: 83%;

13b*: 85%; 13c: 86%; 13c*: 82%; 13d: 82%; 13d*: 81%). All

spectroscopic evidence showed that the protective group

at the labelled primary alcohol function stayed intact dur-

ing the reaction and that there was no oxidation of this

functional group to give another carboxyl group.

The final step on the way to ω-hydroxy carboxylic acids

14a–d is a saponification of the ester group in 13a–d using

a concentrated solution of sodium hydroxide in metha-

nol.⁴⁰According to a monitoring of the reaction, it could

be shown that a reaction time of 5 days (7 days for the

reaction of 13d) is needed to completely remove the pro-

tective group. Adjusting pH of the resulting solution to

1 leads to a precipitation of the resulting ω-hydroxy carbox-

ylic acids, 14a–d, which were collected by filtration and

recrystallized from a mixture of ethyl acetate and light

petroleum in acceptable to excellent yields (14a: 85%; 14a*:

89%; 14b: 89%; 14b*: 93%; 14c: 94%; 14c*: 91%; 14d*: 62%).

middle that results from

a compound in which

1

the corresponding carbon atom is ¹²C and no J_CHcou-

pling occurs. As we used three different samples for the

synthesis of the labelled compounds, we observed three

different values for the isotopic purity, which is easily

accessible by integration of the doublett of tripletts

(¹³CH₂group) and the small triplett (¹²CH₂group). For

all compounds 11a*–14a*, the isotopic purity was 84%,

for 11b*,c*–14b*,c* 92% and for 11d*–14d* 99%. Because

there is no way to exchange ¹³C against ¹²C in the

3 | CONCLUSIONS

In conclusion, we presented high yielding syntheses of

¹³C-labelled ω-hydroxy carboxylic acids with chain

lengths of 14, 18, 22 and 30 carbon atoms, either labelled

at the carboxy functionality or adjacent to the hydroxo

group. The label always is introduced by the use of

390

SCHINK ET AL.

economically benign K¹³CN. In case of carboxy group

labelling, the label could be introduced at a late stage of

the synthesis whereas the label had to be introduced at

an earlier stage if it was situated adjacent to the hydroxyl

group.

(358 mg, 1.28 mmol 6a; 429 mg, 1.28 mmol 6b; 501 mg,

1.28 mg 6c; 420 mg, 0.83 mmol 6d, the latter being

suspended in 15 ml of DMSO). Afterwards, the

corresponding amount of K¹³CN was added (1.35 mmol,

89-mg K¹³CN in case of the reaction of 6a–c; 0.88 mmol,

58-mg K¹³CN in case of the reaction of 6d), and the reac-

tion mixture heated to 70^ꢀC (85^ꢀC for the reaction of 6d)

for 3 days. ω-Bromoalcohols dissolved completely upon

heating. After the reaction time expired, the reaction mix-

ture was allowed to reach room temperature before it

was poured into 50 ml of water and was then extracted

four times with 50-ml ethyl acetate each. In case of the

synthesis of 7d*, the extraction was performed four times

with 60 ml of chloroform each. The combined organic

phases were washed with brine and subsequently with

water, dried over Na₂SO₄, filtered and evaporated to dry-

ness under reduced pressure. Purification of 7a*–c* was

achieved by column chromatography using a mixture of

light petroleum and ethyl acetate (1:3) and yielded the

compounds as colourless, crystalline solids (7a*: 278 mg,

96%; 7b*: 343 mg, 95%; 7c*: 407 mg, 94%). Purification of

7d* was performed by column chromatography using

chloroform as the eluent. The resulting crude product

was then recrystallized from a mixture of light petroleum

and ethanol by first suspending the compound in boiling

light petroleum before adding just the appropriate

amount of ethanol to dissolve the compound. After stand-

ing in the refrigerator overnight, 7d* was obtained as

colourless crystals, which were filtered, washed with

3-ml light petroleum and dried under reduced pressure

(7d*: 356 mg, 95%).

4 | EXPERIMENTAL

4.1 | General

All chemicals and solvents have been purchased from

Sigma-Aldrich, ABCR, Acros Organics, Alfa Aesar, TCI

and VWR and were used without further purifications

after having checked their purity by spectroscopic

methods. Deuterated solvents for NMR spectroscopy and

K¹³CN (99%, cf. supporting information) have been pur-

chased from Deutero GmbH, Kastellaun, Germany.

Anhydrous diethylether and THF were obtained by

heating the respective solvent over sodium/benzophe-

none. Freshly distilled portions were introduced to reac-

tion mixtures in which anhydrous solvents had to be

used. Preparative column chromatography was per-

formed at silica 60 (particle size 0.040–0.063 mm) from

Macherey & Nagel. Colourless compounds were detected

by UV light. IR spectra were recorded at 298 K using a

Shimadzu IR Prestige-21 FTIR spectrometer with a MIR-

acle ATR unit from PIKE Technologies. GC-MS spectra

were recorded by a Finnigan MAT GCQ system equipped

with a Macherey & Nagel GC column (5% dip-

henylsiloxane, 95% dimethylsiloxane, length 30 m, inner

diameter 0.25 mm, film thickness 0.25 μm). NMR spectra

were obtained by the use of either a Bruker Avance

400, a Bruker Avance DRX 600 or a JEOL JNM-ECZ500R

spectrometer. CHN analyses were performed for

compounds that so far had not been described in the

literature using a vario EL III or a vario MICRO

cube analyser both purchased from Elementar

Analysensysteme GmbH.

4.2.1 | [1-¹³C]14-Hydroxytetradecanenitrile

(7a*)

m.p. 51–52^ꢀC; ¹H-NMR (600 MHz, CDCl₃, 298 K): δ

(ppm) = 1.26–1.38 (m, 16 H, HOCH₂CH₂(CH₂)₈CH₂

CH₂CH₂¹³CN), 1.41–1.48 (m, 2 H, CH₂CH₂CH₂¹³CN),

1.54–1.60 (m, 2 H, CH₂CH₂OH), 1.62–1.70 (m, 2 H,

In the following reaction protocols and spectroscopic

data for labelled compounds (marked with an asterisk *)

are shown. Synthetic procedures and analytical data for

all other intermediates and products with a natural distri-

bution of isotopes are given in the supporting

information.

CH₂CH₂¹³CN), 2.34 (dt, ²J_CH2/13C= 9.45 Hz, J_CH2/

3

_CH2= 7.30 Hz,

2

H, CH₂¹³CN), 3.65 (t, ³J_CH2/

_CH2= 6.59 Hz, 2 H, CH₂OH); ¹³C-NMR (151 MHz, CDCl₃,

298 K): δ (ppm) = 17.07 (d, ¹J_13C/C= 56.74 Hz, CH₂¹³CN),

25.32 (d, ²J_13C/C= 2.41 Hz, CH₂CH₂¹³CN), 25.69

(CH₂CH₂CH₂OH),

28.61

(d,

³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CN), 28.71, 29.24, 29.37, 29.42, 29.50, 29.52

(7 ꢁ CH₂), 32.75 (CH₂CH₂OH), 63.01 (CH₂OH), 119.84

(¹³CN); IR (ATR): eν (cm^ꢂ1) = 3383 (m, OH), 2916

(s, CH₂), 2849 (s, CH₂), 2193 (w, ¹³Cꢃ N), 1470 (m, CH₂),

1346 (w), 1051 (m, C─O), 1035 (m), 1012 (m), 989 (m),

970 (m), 721 (m, CH₂), 586 (m); MS (EI): m/z (%) = 225

(5) [M⁺ꢂ H], 207 (12) [M⁺ꢂ H ꢂ H₂O], 193 (12),

4.2 | Synthesis and characterization of

the ω-hydroxynitriles 7a*–d* (modified

after Jiménez et al.³³)

In a 50-ml round flask equipped with a reflux condensor,

the ω-bromoalcohol was suspended in 10 ml of DMSO

SCHINK ET AL.

391

178(28) [M⁺ꢂ H₂O ꢂ C₂H₅], 165(36) [M⁺ꢂ H₂O ꢂ C₃H₆],

153 (17) [M⁺ꢂ H₂O ꢂ C₄H₈], 151 (46) [C₉¹³CH₁₆N⁺],

139 (23) [C₈¹³CH₁₆N⁺], 137 (100) [C₈¹³CH₁₄N⁺],

125 (34) [C₇¹³CH₁₄N⁺], 123 (100) [C₇¹³CH₁₂N⁺], 111 (45)

(CH₂CH₂CH₂OH),

28.63

(d,

³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CN), 28.73, 29.27, 29.40, 29.47, 29.56, 29.58,

29.60, 29.65 (15 ꢁ CH₂), 32.77 (CH₂CH₂OH), 63.02

(CH₂OH), 119.84 (¹³CN); IR (ATR): eν (cm^ꢂ1) = 3379

(m, OH), 2914 (s, CH₂), 2849 (s, CH₂), 2193 (w, ¹³Cꢃ N),

1472 (m, CH₂), 1344 (w), 1057 (m, C─O), 1042 (m),

716 (m, CH₂), 584 (m); MS (EI): m/z (%) = 338 (5) [M⁺],

320 (13) [M⁺ꢂ H₂O], 291 (31) [M⁺ꢂ H₂O ꢂ C₂H₅],

279 (13) [M⁺ꢂ C₃H₇O], 277 (26) [M⁺ꢂ H₂O ꢂ C₃H₇],

263 (15) [M⁺ꢂ H₂O ꢂ C₄H₉], 251 (10) [M⁺ꢂ C₅H₁₁O],

249 (14) [C₁₆¹³CH₃₀N⁺], 237 (12) [C₁₅¹³CH₃₀N⁺],

235 (11) [C₁₅¹³CH₂₈N⁺], 223 (7) [C₁₄¹³CH₂₈N⁺],

221 (11) [C₁₄¹³CH₂₆N⁺], 209 (16) [C₁₃¹³CH₂₆N⁺],

207 (28) [C₁₃¹³CH₂₄N⁺], 195 (8) [C₁₂¹³CH₂₄N⁺],

193 (16) [C₁₂¹³CH₂₂N⁺], 181 (13) [C₁₁¹³CH₂₂N⁺],

179 (15) [C₁₁¹³CH₂₀N⁺], 167 (14) [C₁₀¹³CH₂₀N⁺],

165 (12) [C₁₀¹³CH₁₈N⁺], 151 (18) [C₉¹³CH₁₈N⁺],

151 (21) [C₉¹³CH₁₆N⁺], 139 (20) [C₈¹³CH₁₆N⁺],

137 (37) [C₈¹³CH₁₄N⁺], 125 (31) [C₇¹³CH₁₄N⁺],

123 (43) [C₇¹³CH₁₂N⁺], 111 (66) [C₆¹³CH₁₂N⁺],

98 (64) [C₅¹³CH₁₁N⁺], 97 (100) [C₅¹³CH₁₀N⁺],

83 (97) [C₄¹³CH₈N⁺]; elemental analysis: calcd C 78.34,

H 12.08, N 4,14, found C 78.84, H 12.36, N 3.78.

[C₆¹³CH₁₂N⁺], 98 (43) [C₅¹³CH₁₁N⁺], 97 (71) [C₅

13

CH₁₀N⁺], 83 (69) [C₄¹³CH₈N⁺]; elemental analysis: calcd

C 74.72, H 12.02, N 6.19, found C 74.53, H 12.13, N 6.15.

4.2.2 | [1-¹³C]18-Hydroxyoctadecanenitrile

(7b*)

m.p. 69–70^ꢀC; ¹H-NMR (600 MHz, CDCl₃, 298 K):

δ

(ppm) = 1.25–1.38 (m, 24 H, HOCH₂CH₂

(CH₂)₁₂CH₂CH₂CH₂¹³CN),00201.42–1.49 (m,

H,

CH₂CH₂CH₂¹³CN), 1.54–1.61 (m, 2 H, CH₂CH₂OH),

2

1.62–1.70 (m,

2

H, CH₂CH₂¹³CN), 2.34 (dt,

²J_CH2/13C= 9.45 Hz, ³J_CH2/CH2= 7.30 Hz, 2 H, CH₂¹³CN),

3.65 (t, ³J_CH2/CH2= 6.59 Hz, 2 H, CH₂OH); ¹³C-NMR

1

(151 MHz, CDCl₃, 298 K): δ (ppm) = 17.07 (d, J_13C/

_C= 55.53 Hz, CH₂¹³CN), 25.33 (d, ²J_13C/C= 2.41 Hz,

3

CH₂CH₂¹³CN), 25.70 (CH₂CH₂CH₂OH), 28.62 (d, J_13C/

_C= 3.62 Hz, CH₂CH₂CH₂¹³CN), 28.72, 29.26, 29.40,

29.45, 29.55, 29.58, 29.61 (11 ꢁ CH₂), 32.76 (CH₂CH₂OH),

63.02 (CH₂OH), 119.84 (¹³CN); IR (ATR): eν (cm^ꢂ1) = 3377

(m, OH), 2914 (s, CH₂), 2849 (s, CH₂), 2191 (w, ¹³Cꢃ N),

1472 (m, CH₂), 1346 (w), 1055 (m, C─O), 1045 (m),

717 (m, CH₂), 583 (m); MS (EI): m/z (%) = 282 (3) [M⁺],

264 (5) [M⁺ꢂ H₂O], 235 (12) [M⁺ꢂ H₂O ꢂ C₂H₅],

221 (17) [M⁺ꢂ H₂O ꢂ C₃H₇], 209 (7) [M⁺ꢂ C₄H₉O],

207 (16) [M⁺ꢂ H₂O ꢂ C₄H₈], 195 (8) [C₁₂¹³CH₂₄N⁺],

193 (13) [C₁₂¹³CH₂₂N⁺], 181 (8) [C₁₁¹³CH₂₂N⁺],

179 (13) [C₁₁¹³CH₂₀N⁺], 165 (15) [C₁₀¹³CH₁₈N⁺],

151 (24) [C₉¹³CH₁₆N⁺], 139 (16) [C₈¹³CH₁₆N⁺],

137 (48) [C₈¹³CH₁₄N⁺], 125 (25) [C₇¹³CH₁₄N⁺],

123 (63) [C₇¹³CH₁₂N⁺], 111 (64) [C₆¹³CH₁₂N⁺],

98 (47) [C₅¹³CH₁₁N⁺], 97 (95) [C₅¹³CH₁₀N⁺], 83 (100)

[C₄¹³CH₈N⁺]; elemental analysis: calcd C 76.89, H 12.49,

N 4.96, found C 76.25, H 12.00, N 4.64.

4.2.4 | [1-¹³C]30-Hydroxytriacontanenitrile

(7d*)

m.p. 94–95^ꢀC; ¹H-NMR (600 MHz, CDCl₃, 298 K): δ

(ppm) = 1.22–1.37 (m, 48 H, HOCH₂CH₂(CH₂)₂₄CH₂

CH₂CH₂¹³CN), 1.41–1.38 (m, 2 H, CH₂CH₂CH₂¹³CN),

1.54–1.60 (m, 2 H, CH₂CH₂OH), 1.62–1.71 (m, 2 H,

CH₂CH₂¹³CN), 2.34 (dt, ²J_CH2/13C= 9.45 Hz, J_CH2/

3

_CH2= 7.30 Hz,

2

H, CH₂¹³CN), 3.65 (t, ³J_CH2/

_CH2= 6.59 Hz, 2 H, CH₂OH); ¹³C-NMR (151 MHz,

1

CDCl₃, 298 K): δ (ppm) = 17.06 (d, J_13C/C= 55.53 Hz,

CH₂¹³CN), 25.36 (d, ²J_13C/C= 2.41 Hz, CH₂CH₂¹³CN),

25.72 (CH₂CH₂CH₂OH), 28.66 (d, ³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CN), 28.75, 29.28, 29.42, 29.49, 29.59, 29.69

(23 ꢁ CH₂), 32.80 (CH₂CH₂OH), 63.09 (CH₂OH), 119.86

(¹³CN); IR (ATR): eν (cm^ꢂ1) = 3344 (m, OH), 2914

(s, CH₂), 2849 (s, CH₂), 2192 (w, ¹³Cꢃ N), 1472 (m, CH₂),

1350 (w), 1057 (m, C─O), 1035 (m), 716 (m, CH₂),

584 (m); elemental analysis: calcd C 80.15, H 13.19, N

3.11, found C 79.71, H 12.84, N 3.02.

4.2.3 | [1-¹³C]22-Hydroxydocosanenitrile

(7c*)

m.p. 81–82^ꢀC; ¹H-NMR (600 MHz, CDCl₃, 298 K): δ

(ppm) = 1.24–1.38 (m, 32 H, HOCH₂CH₂(CH₂)₁₆CH₂

CH₂CH₂¹³CN), 1.42–1.48 (m, 2 H, CH₂CH₂CH₂¹³CN),

1.54–1.61 (m, 2 H, CH₂CH₂OH), 1.62–1.71 (m, 2 H,

4.3 | Synthesis and characterization of

the ω-hydroxycarboxylic acids 8a*–d*

(modified after Nacsa and Lambert³⁴)

3

CH₂CH₂¹³CN), 2.34 (dt, ²J_CH2/13C= 9.74 Hz, J_CH2/

_CH2= 7.16 Hz,

2

H, CH₂¹³CN), 3.65 (t, ³J_CH2/

_CH2= 6.59 Hz, 2 H, CH₂OH); ¹³C-NMR (151 MHz, CDCl₃,

298 K): δ (ppm) = 17.07 (d, ¹J_13C/C= 55.53 Hz, CH₂¹³CN),

25.33 (d, ²J_13C/C= 2.41 Hz, CH₂CH₂¹³CN), 25.70

In a 100-ml round flask equipped with a reflux con-

denser, the ω-hydroxynitrile (7a*: 224 mg, 0.99 mmol;

392

SCHINK ET AL.

7b*: 280 mg, 0.99 mmol; 7c*: 200 mg, 0.59 mmol; 7d*:

266 mg, 0.59 mmol) were dissolved in methanol. In case

of the reaction of 7a*–b*, the substrates were dissolved in

35 ml of methanol, and the resulting solution then

treated with 35-ml NaOH (5 M), heated to 70^ꢀC for 18 h

and subsequently refluxed for another 7 h. In case of the

reaction of 7c*–d*, the substrates were treated with a solu-

tion of 2.9-g NaOH in 80 ml of ethanol and the resulting

mixture was refluxed for 24 h for 7c* or 48 h for 7d*. After

the respective mixture was allowed to cool down to room

temperature, it was poured into 150 ml of water and acidi-

fied with half concentrated hydrochloric acid leading to

the precipitation of a colorless solid, which was filtered,

washed with 30 ml of water and dried overnight at 55^ꢀC

in a drying chamber. For purification, the crude products

were transferred into another round flask and 40 ml of hot

ethyl acetate were added. The resulting mixture was fil-

tered over a G3 frit as hot as possible. The flask and the frit

also are treated twice with additional 5 ml of hot ethyl

acetate to completely collect the material. Following this,

the filtrate was concentrated under reduced pressure to

approximately one third of the original volume. The

resulting products 8a*–b* were then recrystallized from a

mixture of light petroleum and ethyl acetate by first

suspending the compound in boiling light petroleum

before adding just the appropriate amount of ethyl acetate

to dissolve the compound. Products 8c*–d* were rec-

rystallized from pure ethyl acetate. After standing in the

refrigerator overnight, 8a*–d* were obtained as colourless

crystals, which were filtered, washed with 3-ml light petro-

leum and dried under reduced pressure (8a*: 216 mg, 89%;

8b*: 272 mg, 91%; 8c*: 196 mg, 93%; 8d*: 241 mg, 87%).

4.3.2 | [1-¹³C]18-Hydroxyoctadecanoic acid

(8b*)

m.p. 98–99^ꢀC; ¹H-NMR (500 MHz, THF, 298 K): δ (ppm)

13

= 1.26–1.37 (m, 26 H, HOCH₂CH₂(CH₂)₁₃CH₂CH₂

COOH), 1.43–1.50 (m, 2 H, CH₂CH₂¹³COOH), 1.53–1.60

3

(m, 2 H, CH₂CH₂OH), 2.20 (quar, J_CH2/CH2= 7.06 Hz,

3

²J_CH2/13C= 7.06 Hz, 2 H, CH₂¹³COOH), 3.46 (t, J_CH2/

_CH2= 6.30 Hz, 2 H, CH₂OH); ¹³C-NMR (151 MHz, THF,

298 K): δ (ppm) = 26.02 (CH₂CH₂¹³COOH), 27.11 (CH₂

CH₂CH₂OH), 30.31 (d, ³J_13C/C= 3.62 Hz, CH₂CH₂

CH₂¹³COOH), 30.52, 30.66, 30.74, 30.76, 30.82, 30.87

1

(11 ꢁ CH₂), 34.27 (CH₂CH₂OH), 34.43 (d, J_13C/

_C= 55.53 Hz, CH₂¹³COOH), 62.72 (CH₂OH), 174.67

(CH₂¹³COOH); IR (ATR): eν (cm^ꢂ1) = 3500–2500 (m, OH),

2913 (s, CH₂), 2847 (s, CH₂), 1659 (m, ¹³C═O), 1470

(s, CH₂), 1402 (w, OH), 1267 (m, CH₂), 1053 (m, C─O),

718 (m, CH₂), 533 (w); elemental analysis: calcd C 72.04,

H 12.04, found C 71.49, H 11.50.

4.3.3 | [1-¹³C]22-Hydroxydocosanoic acid

(8c*)

m.p. 107–108^ꢀC; ¹H-NMR (500 MHz, THF, 298 K): δ

(ppm) = 1.24–1.37 (m, 34 H, HOCH₂CH₂(CH₂)₁₇

CH₂CH₂¹³COOH), 1.42–1.49 (m, 2 H, CH₂CH₂¹³COOH),

3

1.52–1.60 (m, 2 H, CH₂CH₂OH), 2.20 (quar, J_CH2/

2

_CH2= 7.45 Hz, J_CH2/13C= 7.45 Hz, 2 H, CH₂¹³COOH),

3.45 (t, ³J_CH2/CH2= 6.59 Hz, 2 H, CH₂OH); ¹³C-NMR

(151 MHz,

THF,

298 K):

δ

(ppm) = 26.04

(CH₂CH₂¹³COOH), 27.11 (CH₂CH₂CH₂OH), 30.31

(d, ³J_13C/C= 3.62 Hz, CH₂CH₂CH₂¹³COOH), 30.52, 30.66,

30.74, 30.77, 30.82, 30.87 (15 ꢁ CH₂), 34.28 (CH₂CH₂OH),

34.44 (d, ¹J_13C/C= 55.53 Hz, CH₂¹³COOH), 62.72

4.3.1 | [1-¹³C]14-Hydroxytetradecanoic acid

(8a*)

(CH₂OH), 174.68 (CH₂¹³COOH); IR (ATR): eν (cm^ꢂ1

)

= 3500–2500 (m, OH), 2913 (s, CH₂), 2847 (s, CH₂), 1659

(m, ¹³C═O), 1472 (m, CH₂), 1408 (w, OH), 1265

(w, CH₂), 1059 (m, C─O), 716 (m, CH₂), 533 (w);

elemental analysis: calcd C 74.17, H 12.40, found C 73.82,

H 11.84.

m.p. 91–92^ꢀC; ¹H-NMR (500 MHz, THF, 298 K): δ (ppm)

= 1.26–1.37

(m,

18

H,

HOCH₂CH₂(CH₂)₉CH₂

CH₂¹³COOH), 1.43–1.50 (m, 2 H, CH₂CH₂¹³COOH),

3

1.53–1.60 (m, 2 H, CH₂CH₂OH), 2.20 (quar, J_CH2/

_CH2= 7.26 Hz, ²J_CH2/13C= 7.26 Hz, 2 H, CH₂¹³COOH),

3.46 (t, ³J_CH2/CH2= 6.30 Hz, 2 H, CH₂OH); ¹³C-NMR

4.3.4 | [1-¹³C]30-Hydroxytriacontanoic acid

(151 MHz, THF, 298 K):

δ

(ppm) = 26.03 (CH₂

(8d*)

3

CH₂¹³COOH), 27.11(CH₂CH₂CH₂OH), 30.30 (d, J_13C/

_C= 3.62 Hz, CH₂CH₂CH₂¹³COOH), 30.51, 30.65, 30.73,

30.76, 30.79 (7 ꢁ CH₂), 30.85, 34.26 (CH₂CH₂OH), 34.43

(d, ¹J_13C/C= 55.53 Hz, CH₂¹³COOH), 62.72 (CH₂OH),

174.67 (CH₂¹³COOH); IR (ATR): eν (cm^ꢂ1) = 3500–2500

(m, OH), 2913 (m, CH₂), 2845 (m, CH₂), 1643 (s, ¹³C═O),

1470 (s, CH₂), 1410 (w, OH), 1275 (m, CH₂), 1049 (m,

C─O), 718 (m, CH₂), 529 (m); elemental analysis: calcd C

68.94, H 11.50, found C 68.63, H 11.54.

m.p. 107–109^ꢀC; ¹H-NMR (500 MHz, THF, 298 K): δ

(ppm) = 1.24–1.38

(m,

50

H,

HOCH₂

CH₂(CH₂)₂₅CH₂CH₂¹³COOH), 1.42–1.50 (m,

2

H,

CH₂CH₂¹³COOH), 1.52–1.61 (m, 2 H, CH₂CH₂OH), 2.20

(quar, ³J_CH2/CH2= 7.45 Hz, ²J_CH2/13C= 7.45 Hz, 2 H,

CH₂¹³COOH), 3.45 (t, ³J_CH2/CH2= 6.59 Hz, 2 H, CH₂OH);

¹³C-NMR (151 MHz, THF, 298 K): δ (ppm) = 26.03

(CH₂CH₂¹³COOH), 27.12 (CH₂CH₂CH₂OH), 30.31

SCHINK ET AL.

393

(d, ³J_13C/C= 3.62 Hz, CH₂CH₂CH₂¹³COOH), 30.52, 30.67,

30.74, 30.82, 30.87 (23 ꢁ CH₂), 34.29 (CH₂CH₂OH), 34.42

(d, ¹J_13C/C= 55.53 Hz, CH₂¹³COOH), 62.72 (CH₂OH),

174.68 (¹³COOH); IR (ATR): eν (cm^ꢂ1) = 3344 (m, OH),

2918 (s, CH₂), 2846 (s, CH₂), 1462 (m, CH₂), 1442

(m, OH), 1051 (m, C─O), 1016 (m), 997 (w),

727 (m, CH₂); elemental analysis: calcd C 76.91, H 12.87,

found C 77.07, H 12.58.

(CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3078 (w, ═CH₂),

2922 (s, CH₂), 2853 (s, CH₂), 2193 (w, ¹³Cꢃ N), 1640

(m, C═C), 1464 (m, CH₂), 993 (m, ─HC═CH₂),

908 (m, ─HC═CH₂), 721 (m, CH₂); MS (EI): m/z (%)

= 221

(3)

[M⁺ꢂ H],

207

(4)

[M⁺ꢂ CH₃],

193 (14) [M⁺ꢂ C₂H₅], 179 (20) [M⁺ꢂ C₃H₇],

165 (18) [C₁₀¹³CH₁₈⁺], 151 (24) [C₉¹³CH₁₆⁺],

137 (65) [C₈¹³CH₁₄⁺], 123 (100) [C₇¹³CH₁₂⁺],

111 (16) [C₆¹³CH₁₂⁺], 109 (25) [C₆¹³CH₁₀⁺],

97 (37) [C₅¹³CH₁₀⁺], 95 (57) [C₅¹³CH₈⁺], 83 (48) [C₄¹³C

H₈⁺]; elemental analysis: calcd C 81.46, H 12.24, N 6.30,

found C 81.39, H 12.17, N 6.30.

4.4 | Synthesis and characterization of

the ω-alkenylnitriles 9a*–d* (modified after

Rosillo et al.⁴¹)

4.4.2 | [1-¹³C]Nonadec-18-enenitrile (9b*)

In a 25-ml round flask, 3.02 mmol of the corresponding

ω-bromoalkene (831-mg 2e, 1.001-g 2f, 1.170-g 2g,

1.509-g 2h) were treated with 8 ml of DMSO and subse-

quently with 3.18 mmol (210 mg) K¹³CN. The reaction

mixture was then heated to 85^ꢀC for 3 days. After the

pale yellow reaction mixture was cooled to room temper-

ature, it was poured into 40 ml of water and extracted

four times with 40 ml of ethyl acetate each. The com-

bined organic phases were then washed twice with 40 ml

of water, dried over Na₂SO₄and filtered, and the solvent

was then evaporated under reduced pressure. In case of

oily crude reaction products (9a*–9c*), they were purified

by column chromatography using a mixture of light

petroleum and ethyl acetate (1:1) as the eluent yielding

9a* as a colourless oil and 9b*–c* as colourless solids. In

case of 9d*, the crude reaction product already was solid

and purified by recrystallization from light petroleum.

Crystallization was achieved by keeping the solution in

the refrigerator overnight. Pure 9d* was then collected by

filtration and dried under reduced pressure. Obtained

yields were 591-mg (88%) 9a*, 765-mg (91%) 9b*, 960-mg

(95%) 9c* and 1.201-g (89%) 9d*.

m.p. 29–30^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.23–1.47

(m,

26

H,

N¹³CCH₂

H,

CH₂(CH₂)₁₃CH₂CH═CH₂),

1.62–1.71

(m,

2

CH₂CH₂¹³CN), 2.01–2.08 (m, 2 H, CH₂CH═CH₂), 2.34

(dt, ²J_CH2/13C= 9.74 Hz, ³J_CH2/CH2= 7.16 Hz,

2

H,

CH₂¹³CN), 4.91–5.04 (m, 2 H, CH₂CH═CH₂), 5.82

(ddt, ³J_CH/CH2[E]= 17.11 Hz, ³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/CH2= 6.66 Hz,

1

H, CH₂CH═CH₂); ¹³C-NMR

1

(126 MHz, CDCl₃, 298 K): δ (ppm) = 17.08 (d, J_13C/

_C= 56.74 Hz, CH₂¹³CN), 25.35 (d, ²J_13C/C= 2.41 Hz,

CH₂CH₂¹³CN),

28.64

(d,

³J_13C/C= 3.66 Hz,

CH₂CH₂CH₂¹³CN), 28.74, 28.93, 29.13, 29.28, 29.48, 29.59

(12 ꢁ CH₂),

33.80

119.84

(CH₂CH═CH₂),

(CH₂¹³CN),

114.05

139.24

(CH₂CH═CH₂),

(CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3077 (w, ═CH₂),

2914 (s, CH₂), 2849 (s, CH₂), 2189 (w, ¹³Cꢃ N), 1643

(m, C═C), 1472 (m, CH₂), 993 (m, ─HC═CH₂),

926 (m, ─HC═CH₂), 718 (m, CH₂); MS (EI): m/z (%)

= 278 (4) [M⁺], 263 (7) [M⁺ꢂ CH₃], 249 (19) [M⁺ꢂ C₂H₅],

235 (24) [M⁺ꢂ C₃H₇], 221 (18) [M⁺ꢂ C₄H₉],

207 (18) [C₁₃¹³CH₂₄⁺], 192 (20) [C₁₂¹³CH₂₂⁺],

178 (19) [C₁₁¹³CH₂₀⁺], 165 (18) [C₁₀¹³CH₁₈⁺],

151 (30) [C₉¹³CH₁₆⁺], 137 (71) [C₈¹³CH₁₄⁺], 123 (100)

[C₇¹³CH₁₂⁺], 111 (30) [C₆¹³CH₁₂⁺], 97 (49) [C₅¹³CH₁₀⁺],

83 (63) [C₄¹³C H₈⁺]; elemental analysis: calcd C 82.30, H

12.67, N 5.03, found C 82.14, H 12.44, N 4.82.

4.4.1 | [1-¹³C]Pentadec-14-enenitrile (9a*)

¹H-NMR (500 MHz, CDCl₃, 298 K): δ (ppm) = 1.24–1.48

(m, 18 H, N¹³CCH₂CH₂(CH₂)₉CH₂CH═CH₂), 1.62–1.70

(m,

2

H, CH₂CH₂¹³CN), 2.02–2.08 (m,

2

H,

CH₂CH═CH₂), 2.34 (dt, ²J_CH2/13C= 9.45 Hz, J_CH2/

_CH2= 7.02 Hz, 2 H, CH₂¹³CN), 4.91–5.03 (m, 2 H,

4.4.3 | [1-¹³C]Tricos-22-enenitrile (9c*)

3

CH₂CH═CH₂), 5.82 (ddt, ³J_CH/CH2[E]= 17.04 Hz, J_CH/

m.p. 45–46^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

3

_CH2[Z]= 10.31 Hz,

³J_CH/CH2= 6.66 Hz,

1

H,

(ppm) = 1.23–1.48

(m,

34

H,

N¹³CCH₂CH₂

CH₂CH═CH₂); ¹³C-NMR (126 MHz, CDCl₃, 298 K): δ

(ppm) = 17.08 (d, ¹J_13C/C= 55.53 Hz, CH₂¹³CN), 25.35

(CH₂)₁₇CH₂CH═CH₂), 1.61–1.72 (m, 2 H, CH₂CH₂¹³CN),

2.00–2.09

(m,

2

H,

CH₂CH═CH₂),

2.34

H,

(d, ²J_13C/C= 2.17 Hz, CH₂CH₂¹³CN), 28.64 (d, J_13C/

(dt, ²J_CH2/13C= 9.45 Hz, ³J_CH2/CH2= 7.02 Hz,

2

3

_C= 3.62 Hz, CH₂CH₂CH₂¹³CN), 28.74, 28.91, 29.11,

29.27, 29.46, 29.53 (8 ꢁ CH₂), 33.79 (CH₂CH═CH₂),

114.07 (CH₂CH═CH₂), 119.84 (CH₂¹³CN), 139.22

CH₂¹³CN), 4.90–5.03 (m, 2 H, CH₂CH═CH₂), 5.82

(ddt, ³J_CH/CH2[E]= 16.97 Hz, ³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/CH2= 6.73 Hz,

1

H, CH₂CH═CH₂); ¹³C-NMR

394

SCHINK ET AL.

1

(126 MHz, CDCl₃, 298 K): δ (ppm) = 17.09 (d, J_13C/

_C= 56.74 Hz, CH₂¹³CN), 25.36 (d, ²J_13C/C= 2.41 Hz,

equipped with a reflux condenser and were dissolved in a

solution of 8.8-g (0.22 mol) NaOH in 200 ml of ethanol.

The reaction mixture was then refluxed for 24 h. The

reaction mixture was then poured into 200 ml of water

and acidified with half concentrated hydrochloric acid. In

case of the reaction of 9a*, the resulting solution was

then divided into equal shares each of those being

extracted four times with 50 ml of ethyl acetate each. The

combined organic phases were then washed with water,

dried over Na₂SO₄and filtered, and the solvent was evap-

orated under reduced pressure. The crude product 10a*

was purified by column chromatography using a mixture

of ethyl acetate and light petroleum (1:2) as the eluent

producing 10a* as a colourless crystalline material after

the solvent was evaporated (10a*: 640 mg, 96%). In case

of the reaction of 9b*–d*, acidification of the reaction

mixture led to the precipitation of a white solid, which

was filtered, washed with 50 ml of water and dried under

reduced pressure. The resulting products 10b*–d* were

then recrystallized from a mixture of light petroleum and

ethyl acetate by first suspending the compound in boiling

light petroleum before adding just the appropriate

amount of ethyl acetate to dissolve the compound. After

standing in the refrigerator overnight, 10b*–d* were

obtained as colourless crystals, which were filtered,

washed with 5 ml of cooled light petroleum and dried

under reduced pressure (10b*: 764 mg, 93%; 10c*:

888 mg, 91%; 10d*: 1.196 g, 93%).

CH₂CH₂¹³CN),

28.66

(d,

³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CN), 28.76, 28.94, 29.15, 29.29, 29.50,

29.58, 29.63, 29.68 (16 ꢁ CH₂), 33.81 (CH₂CH═CH₂),

114.05 (CH₂CH═CH₂), 119.85 (CH₂¹³CN), 139.26

(CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3075 (w, ═CH₂),

2913 (s, CH₂), 2849 (s, CH₂), 2191 (w, ¹³Cꢃ N), 1641 (m,

C═C), 1472 (m, CH₂), 990 (m, ─HC═CH₂), 914 (m,

─HC═CH₂), 718 (m, CH₂); MS (EI): m/z (%) = 334

(7) [M⁺], 305 (25) [M⁺ꢂ C₂H₅], 291 (44) [M⁺ꢂ C₃H₇],

277 (38) [M⁺ꢂ C₄H₉], 263 (35) [M⁺ꢂ C₅H₁₁],

249

221

(31)

(27)

[C₁₇H₃₀⁺],

[C₁₅H₂₆⁺],

235

207

(26)

(27)

[C₁₆H₂₈⁺],

[C₁₃¹³CH₂₄⁺],

193 (20) [C₁₂¹³CH₂₂⁺], 181 (22) [C₁₁¹³CH₂₂⁺],

179 (22) [C₁₁¹³CH₂₀⁺], 167 (24) [C₁₀¹³CH₂₀⁺],

165 (29) [C₁₀¹³CH₁₈⁺], 151 (46) [C₉¹³CH₁₆⁺],

137 (91) [C₈¹³CH₁₄⁺], 123 (100) [C₇¹³CH₁₂⁺],

111 (64) [C₆¹³CH₁₂⁺], 97 (87) [C₅¹³CH₁₀⁺], 83 (69) [C₄¹³C

H₈⁺]; elemental analysis: calcd C 82.86, H 12.95, N 4.19,

found C 82.79, H 12.69, N 4.10.

4.4.4 | [1-¹³C]Hentriacont-30-enenitrile

(9d*)

m.p. 69–70^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.23–1.47

(m,

50

H,

N¹³CCH₂CH₂

(CH₂)₂₅CH₂CH═CH₂), 1.61–1.71 (m, 2 H, CH₂CH₂¹³CN),

2.00–2.09

(m,

2

H,

CH₂CH═CH₂),

2.34

H,

(dt, ²J_CH2/13C= 9.45 Hz, ³J_CH2/CH2= 7.02 Hz,

2

CH₂¹³CN), 4.90–5.04 (m, 2 H, CH₂CH═CH₂), 5.82 (ddt,

³J_CH/CH2[E]= 16.90 Hz, ³J_CH/CH2[Z]= 10.31 Hz, ³J_CH/

_CH2= 6.73 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

4.5.1 | [1-¹³C]Pentadec-14-enoic acid (10a*)

m.p. 50–51^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.22–1.43 (m, 18 H, HOO¹³CCH₂CH₂

1

CDCl₃, 298 K): δ (ppm) = 17.06 (d, J_13C/C= 55.53 Hz,

CH₂¹³CN), 25.36 (d, ²J_13C/C= 2.41 Hz, CH₂CH₂¹³CN),

28.66 (d, ³J_13C/C= 3.62 Hz, CH₂CH₂CH₂¹³CN), 28.76,

28.94, 29.15, 29.29, 29.50, 29.58, 29.61, 29.69 (24 ꢁ CH₂),

33.82 (CH₂CH═CH₂), 114.05 (CH₂CH═CH₂), 119.84

(CH₂)₉CH₂CH═CH₂), 1.59–1.68 (m, 2 H, CH₂CH₂

13

COOH), 2.00–2.09 (m, 2 H, CH₂CH═CH₂), 2.36 (quar,

³J_CH2/CH2= 7.26 Hz, ²J_CH2/13C= 7.26 Hz, 2 H, CH₂

13

COOH), 4.90–5.04 (m,

(ddt, ³J_CH/CH2[E]= 17.11 Hz, ³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/CH2= 6.66 Hz, H, CH₂CH═CH₂); ¹³C-NMR

(126 MHz, CDCl₃,

2 H, CH₂CH═CH₂), 5.82

(CH₂¹³CN), 139.26 (CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1

)

= 3076 (w, ═CH₂), 2914 (s, CH₂), 2847 (s, CH₂), 2195

(w, ¹³Cꢃ N), 1641 (m, C═C), 1472 (m, CH₂),

991 (m, ─HC═CH₂), 912 (m, ─HC═CH₂), 720 (m, CH₂);

elemental analysis: calcd C 83.56, H 13.31, N 3.13, found

C 83.55, H 12.81, N 3.01.

1

298 K):

δ

(ppm) = 24.65

3

(CH₂CH₂¹³COOH), 28.93 (CH₂), 29.04 (d, J_13C/

_C= 3.62 Hz, CH₂CH₂CH₂¹³COOH), 29.14, 29.22, 29.41,

29.49,

29.55,

29.57,

34.03

114.06

29.59

(d,

(CH₂CH═CH₂),

(7 ꢁ CH₂),

¹J_13C/C= 56.74 Hz,

139.26

33.81

(CH₂CH═CH₂),

CH₂¹³COOH),

4.5 | Synthesis and characterization of

the ω-alkenylcarboxylic acids 10a*–d*

(modified after Coxon et al.⁴²)

(CH₂CH═CH₂), 180.17 (¹³COOH); IR (ATR): eν (cm^ꢂ1

)

= 3300–2500 (m, OH), 3077 (w, ═CH₂), 2914 (s, CH₂),

2847 (s, CH₂), 1654 (s, ¹³C═O), 1643 (m, C═C), 1462

(m, CH₂), 1409 (m, OH), 1277 (m, CH₂),

991 (m, ─HC═CH₂), 939 (m, OH), 912 (m, ─HC═CH₂),

727 (m, CH₂), 687 (m), 548 (m); MS (EI): m/z (%) = 241

(1) [M⁺], 233 (6) [M⁺ꢂ H₂O], 194 (5) [C₁₂¹³CH₂₁O⁺],

A

total of 2.76 mmol of the corresponding

ω-alkenylnitrile (614-mg 9a*, 769-mg 9b*, 924-mg 9c*,

1.233-g 9d*) were placed in a 250-ml round flask

SCHINK ET AL.

395

180 (7) [C₁₁¹³CH₁₉O⁺], 166 (7) [C₁₀¹³CH₁₇O⁺],

152 (14) [C₉¹³CH₁₅O⁺], 138 (18) [C₈¹³CH₁₃O⁺],

124 (30) [C₇¹³CH₁₁O⁺], 111 (24) [C₆¹³CH₁₀O⁺],

99 (66) [C₄¹³CH₆O₂⁺], 81 (100) [C₅H₇⁺]; elemental analy-

sis: calcd C 75.05, H 11.69, found C 74.99, H 11.59.

4.5.4 | [1-¹³C]Hentriacont-30-enoic acid

(10d*)

m.p. 90–91^ꢀC; ¹H-NMR (500 MHz, DMSO, 373 K): δ

(ppm) = 1.10–1.44 (m, 50 H, HOO¹³CCH₂CH₂(CH₂)₂₅

CH₂CH═CH₂), 1.48–1.60 (m, 2 H, CH₂CH₂¹³COOH),

2.02 (q, ³J_CH2/CH2= 6.87 Hz, 2 H, CH₂CH═CH₂), 2.18

(quar, ³J_CH2/CH2= 7.45 Hz, ²J_CH2/13C= 7.45 Hz, 2 H,

CH₂¹³COOH), 4.89–5.04 (m, 2 H, CH₂CH═CH₂), 5.80

4.5.2 | [1-¹³C]Nonadec-18-enoic acid (10b*)

m.p. 65–66^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

3

(ppm) = 1.21–1.44

(m,

26

H,

HOO¹³CCH₂CH₂

(ddt, J_CH/CH2[E]= 17.18 Hz, J_CH/CH2[Z]= 9.74 Hz, J_CH/

_CH26+= 6.87 Hz,

H, CH₂CH═CH₂); ¹³C-NMR

(126 MHz, CDCl₃,

13

(CH₂)₁₃CH₂CH═CH₂), 1.59–1.69 (m, 2 H, CH₂CH₂

COOH), 2.01–2.09 (m, 2 H, CH₂CH═CH₂), 2.35 (quar,

1

298 K):

δ

(ppm) = 24.03

³J_CH2/CH2= 7.45 Hz, ²J_CH2/13C= 7.45 Hz, 2 H, CH₂

(CH₂CH₂¹³COOH), 27.80, 27.93 (2 ꢁ CH₂), 28.08

13

COOH), 4.90–5.04 (m, 2 H, CH₂CH═CH₂), 5.82 (ddt, ³J_CH/

(d, J_13C/C= 2.4 Hz, CH₂CH₂CH₂¹³COOH), 28.15, 28.27,

3

1

_CH2[E]= 16.97 Hz,

³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/

28.39 (22 ꢁ CH₂), 32.50 (CH₂CH═CH₂), 33.28 (d, J_13C/

_CH2= 6.73 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

CDCl₃, 298 K): δ (ppm) = 24.67 (CH₂CH₂¹³COOH), 28.95

_C= 55.53 Hz, CH₂¹³COOH), 113.69 (CH₂CH═CH₂),

138.18 (CH₂CH═CH₂), 173.49 (¹³COOH); IR (ATR): eν

(cm^ꢂ1) = 3300–2500 (m, OH), 3073 (w, ═CH₂), 2914 (s,

CH₂), 2847 (s, CH₂), 1657 (s, ¹³C═O), 1643 (m, C═C),

1462 (m, CH₂), 1409 (m, OH), 1277 (m, CH₂),

991 (m, ─HC═CH₂), 943 (m, OH), 912 (m, ─HC═CH₂),

720 (m, CH₂), 689 (m), 544 (m); elemental analysis: calcd

C 80.15, H 12.98, found C 80.09, H 12.81.

3

(CH₂), 29.06 (d, J_13C/C= 3.62 Hz, CH₂CH₂CH₂¹³COOH),

29.16, 29.24, 29.43, 29.51, 29.59, 29.62, 29.67 (11 ꢁ CH₂),

33.83 (CH₂CH═CH₂), 34.02 (d, ¹J_13C/C= 55.53 Hz,

CH₂¹³COOH),

114.06

(CH₂CH═CH₂),

139.27

(CH₂CH═CH₂), 180.01 (¹³COOH); IR (ATR): eν (cm^ꢂ1

)

= 3300–2500 (m, OH), 3077 (w, ═CH₂), 2914 (s, CH₂),

2847 (s, CH₂), 1657 (s, ¹³C═O), 1643 (m, C═C), 1462

(m, CH₂), 1410 (m, OH), 1273 (m, CH₂),

991 (m, ─HC═CH₂), 941 (m, OH), 912 (m, ─HC═CH₂),

720 (m, CH₂), 687 (m), 548 (m); elemental analysis: calcd

C 77.05, H 12.20, found C 77.01, H 11.88.

4.6 | Synthesis and characterization of

the ω-alkenylalcohols 11a*–d* (modified

after Franchini et al.⁴³)

4.5.3 | [1-¹³C]Tricos-22-enoic acid (10c*)

In a 100-ml two-necked flask equipped with a reflux con-

denser and a septum, 448-mg (11.8 mmol) LiAlH₄were

suspended in 15 ml of anhydrous THF under a nitrogen

atmosphere. After the mixture was cooled to 0^ꢀC with an

ice bath, a solution of 2.36 mmol of the corresponding

ω-alkenylcarboxylic acid (570-mg 10a*, 702-mg 10b*,

835-mg 10c*, 1.100-g 10d*) in 15 ml of anhydrous THF

was added dropwise with a syringe so slowly that the

reaction mixture only boiled smoothly. After the addition

was completed, the suspension was heated to reflux for

another 4 h. Then the reaction mixture was again cooled

down to 0^ꢀC with an ice bath before water was added

dropwise to decompose excess LiAlH₄. Afterwards, the

mixture was transferred into 50 ml (250 ml in case of

the reaction of 10d*) of water and acidified with half con-

centrated hydrochloric acid to dissolve the formed

Al(OH)₃. If 10a*–c* are reacted, the aqueous phase was

now extracted four times with 50 ml of diethylether each;

the combined organic phases are washed with a diluted

solution of NaHCO₃and then with brine. The organic

phases were then dried over Na₂SO₄, filtered and evapo-

rated under reduced pressure. Purification of the crude

products 11a*–c* was performed by column chromatog-

m.p. 74–75^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.20–1.43 (m, 34 H, HOO¹³CCH₂CH₂

13

(CH₂)₁₇CH₂CH═CH₂), 1.59–1.69 (m, 2 H, CH₂CH₂

COOH), 2.00–2.09 (m, 2 H, CH₂CH═CH₂), 2.36 (quar,

³J_CH2/CH2= 7.45 Hz, ²J_CH2/13C= 7.45 Hz, 2 H, CH₂

13

COOH), 4.91–5.03 (m,

(ddt, ³J_CH/CH2[E]= 17.04 Hz, ³J_CH/CH2[Z]= 10.17 Hz,

³J_CH/CH2= 6.44 Hz, H, CH₂CH═CH₂); ¹³C-NMR

(126 MHz, CDCl₃, 298 K): (ppm) = 24.67

2 H, CH₂CH═CH₂), 5.82

1

δ

(CH₂CH₂¹³COOH), 28.95 (CH₂), 29.06 (d, J_13C/

_C= 3.62 Hz, CH₂CH₂CH₂¹³COOH), 29.16, 29.24, 29.44,

29.52, 29.59, 29.62, 29.64, 29.69 (15 ꢁ CH₂), 33.83

3

(CH₂CH═CH₂),

CH₂¹³COOH),

34.02

114.06

(d,

(CH₂CH═CH₂),

¹J_13C/C= 55.42 Hz,

139.28

(CH₂CH═CH₂), 179.89 (¹³COOH); IR (ATR): eν (cm^ꢂ1

)

= 3300–2500 (m, OH), 3075 (w, ═CH₂), 2914 (s, CH₂),

2847 (s, CH₂), 1657 (s, ¹³C═O), 1643 (m, C═C), 1462

(m, CH₂), 1409 (m, OH), 1282 (m, CH₂),

990 (m, ─HC═CH₂), 942 (m, OH), 912 (m, ─HC═CH₂),

720 (m, CH₂), 687 (m), 546 (m); elemental analysis: calcd

C 78.41, H 12.54, found C 78.09, H 12.26.

396

SCHINK ET AL.

3

raphy using a mixture of diethylether and light petroleum

(1:5 for 11a*, 1:1 for 11b*–c*) as the eluent producing the

products as colourless crystalline compounds after evapo-

ration of the solvent (11a*: 483 mg, 90%; 11b*: 642 mg,

96%; 11c*: 753 mg, 94%). In case of the reaction of 10d*,

acidification of the reaction mixture led to a colourless

precipitate, which was collected by filtration. The

resulting crude product 11d* was then recrystallized from

a mixture of light petroleum and ethyl acetate by first

suspending the compound in boiling light petroleum

before adding just the appropriate amount of ethyl ace-

tate to dissolve the compound. After standing in the

refrigerator overnight, 11d* was obtained as colourless

crystals, which were filtered and dried under reduced

pressure (11d*: 981 mg, 92%).

2.01–2.09 (m, 2 H, CH₂CH═CH₂), 3.64 (dt, J_CH2/

_CH2= 6.59 Hz, J_13CH2/13C= 140.90 Hz, 2 H, ¹³CH₂OH),

4.90–5.03 (m, 2 H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2

1

3

_[E]= 17.11 Hz,

³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/

_CH2= 6.66 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

CDCl₃, 298 K): δ (ppm) = 25.72 (CH₂CH₂¹³CH₂OH),

28.94, 29.15 (2 ꢁ CH₂), 29.43 (d, ³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CH₂OH), 29.50, 29.60, 29.67 (10 ꢁ CH₂),

32.79 (d, ¹J_13C/C= 36.22 Hz, CH₂¹³CH₂OH), 33.81

(CH₂CH═CH₂), 63.07 (¹³CH₂OH), 114.05 (CH₂CH═CH₂),

139.27 (CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3319

(m, OH), 3077 (w, ═CH₂), 2916 (s, CH₂), 2847 (s, CH₂),

1641 (m, C═C), 1462 (m, CH₂), 1362 (w, CH₂), 1042

(m, ¹³C─O), 991 (m, ─HC═CH₂), 920 (w),

912 (m, ─HC═CH₂), 720 (m, CH₂), 644 (m); MS (EI): m/z

(%) = 282 (1) [M⁺ꢂ H], 265 (1) [M⁺ꢂ H₂O],

236 (1) [M⁺ꢂ H₂O ꢂ C¹³CH₄], 222 (1) [M⁺ꢂ H₂O ꢂ C₂

13

4.6.1 | [1-¹³C]Pentadec-14-en-1-ol (11a*)

CH₆], 209 (1) [M⁺ꢂ H₂O ꢂ C₄H₈], 208 (1) [M⁺ꢂ H₂O ꢂ

C₃¹³CH₈], 194 (1) [C₁₄H₂₆⁺], 181 (1) [C₁₂¹³CH₂₄⁺],

180 (1) [C₁₃H₂₄⁺], 167 (1) [C₁₁¹³CH₂₂⁺], 166 (1)

[C₁₂H₂₂⁺], 165 (1) [C₁₂H₂₁⁺], 153 (1) [C₁₀¹³CH₂₀⁺],

152 (2) [C₁₁H₂₀⁺], 151 (1) [C₁₁H₁₉⁺], 139 (3) [C₉¹³CH₁₈⁺],

138 (5) [C₁₀H₁₈⁺], 137 (4) [C₁₀H₁₇⁺], 125 (7) [C₈¹³CH₁₆⁺],

124 (12) [C₉H₁₆⁺], 123 (11) [C₉H₁₅⁺], 111 (7)

[C₇¹³CH₁₄⁺], 110 (12) [C₈H₁₄⁺], 109 (11) [C₈H₁₃⁺],

97 (23) [C₆¹³CH₁₂⁺], 96 (37) [C₇H₁₂⁺], 95 (37) [C₇H₁₁⁺],

82 (59) [C₆H₁₀⁺], 81 (100) [C₆H₉⁺]; elemental analysis:

calcd C 80.85, H 13.51, found C 80.49, H 13.20.

m.p. 34–35^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.21–1.42 (m, 20 H, HO¹³CH₂CH₂(CH₂)₁₀

CH₂CH═CH₂), 1.50–1.60 (m, 2 H, CH₂¹³CH₂OH), 1.98–

3

2.06 (m,

2

H, CH₂CH═CH₂), 3.62 (dt, J_CH2/

_CH2= 6.59 Hz, J_13CH2/13C= 140.90 Hz, 2 H, ¹³CH₂OH),

1

3

4.88–5.02 (m, 2 H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2

_[E]= 17.11 Hz,

³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/

_CH2= 6.66 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

CDCl₃, 298 K): δ (ppm) = 25.72 (CH₂CH₂¹³CH₂OH),

28.93, 29.14 (2 ꢁ CH₂), 29.42 (d, ³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CH₂OH), 29.50, 29.59, 29.63 (6 ꢁ CH₂),

32.78 (d, ¹J_13C/C= 37.42 Hz, CH₂¹³CH₂OH), 33.81

(CH₂CH═CH₂), 63.07 (¹³CH₂OH), 114.06 (CH₂CH═CH₂),

139.26 (CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3319

(m, OH), 3067 (w, ═CH₂), 2914 (s, CH₂), 2849 (s, CH₂),

1642 (m, C═C), 1462 (m, CH₂), 1342 (w, CH₂), 1045

(m, ¹³C─O), 990 (m, ─HC═CH₂), 912 (m, ─HC═CH₂),

720 (m, CH₂), 644 (m); MS (EI): m/z (%) = 226

(1) [M⁺ꢂ H], 209 (1) [M⁺ꢂ H₂O], 194 (1) [M⁺ꢂ ¹³CH₄O],

181 (1) [M⁺ꢂ H₂O ꢂ C₂H₄], 180 (1) [M⁺ꢂ H₂O ꢂ ¹³C₂H₄],

4.6.3 | [1-¹³C]Tricos-22-en-1-ol (11c*)

m.p. 66–67^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.21–1.42

(m,

36

H,

HO¹³CH₂CH₂

(CH₂)₁₈CH₂CH═CH₂), 1.52–1.62 (m, 2 H, CH₂¹³CH₂OH),

3

2.00–2.08 (m, 2 H, CH₂CH═CH₂), 3.64 (dt, J_CH2/

_CH2= 6.59 Hz, J_13CH2/13C= 140.90 Hz, 2 H, ¹³CH₂OH),

1

3

4.90–5.03 (m, 2 H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2

_[E]= 17.11 Hz,

³J_CH/CH2[Z]= 10.24 Hz,

³J_CH/

167

(1)

[C₁₁¹³CH₂₂⁺],

166

(1)

[C₁₂H₂₂⁺],

_CH2= 6.66 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

CDCl₃, 298 K): δ (ppm) = 25.72 (CH₂CH₂¹³CH₂OH),

28.94, 29.15 (2 ꢁ CH₂), 29.43 (d, ³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CH₂OH), 29.51, 29.61, 29.69 (14 ꢁ CH₂),

32.78 (d, ¹J_13C/C= 37.42 Hz, CH₂¹³CH₂OH), 33.82

(CH₂CH═CH₂), 63.07 (¹³CH₂OH), 114.05 (CH₂CH═CH₂),

139.26 (CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3321

(m, OH), 3077 (w, ═CH₂), 2917 (s, CH₂), 2847 (s, CH₂),

1641 (m, C═C), 1462 (m, CH₂), 1364 (w, CH₂), 1026

(m, ¹³C─O), 991 (m, ─HC═CH₂), 920 (w),

912 (m, ─HC═CH₂), 720 (m, CH₂), 644 (m); MS (EI): m/z

152 (1) [C₁₁H₂₀⁺], 151 (1) [C₁₁H₁₉⁺], 125 (3) [C₈¹³CH₁₆⁺],

124 (4) [C₉H₁₆⁺], 123 (3) [C₉H₁₅⁺], 111 (5) [C₇¹³CH₁₄⁺],

110 (10) [C₈H₁₄⁺], 109 (8) [C₈H₁₃⁺], 97 (15) [C₆¹³CH₁₂⁺],

96 (30) [C₇H₁₂⁺], 95 (34) [C₇H₁₁⁺], 82 (66) [C₆H₁₀⁺],

81 (100) [C₆H₉⁺]; elemental analysis: calcd C 79.67, H

13.30, found C 79.45, H 13.02.

4.6.2 | [1-¹³C]Nonadec-18-en-1-ol (11b*)

m.p. 53–54^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.22–1.42 (m, 28 H, HO¹³CH₂CH₂(CH₂)₁₄

(%) = 340 (1) [M⁺

+

H], 321 (2) [M⁺ꢂ H₂O],

293 (2) [M⁺ꢂ H₂O ꢂ C₂H₄], 265 (2) [M⁺ꢂ H₂O ꢂ C₄H₈],

CH₂CH═CH₂), 1.52–1.62 (m,

2

H, CH₂¹³CH₂OH),

250 (1) [M⁺ꢂ H₂O ꢂ C₄¹³CH₁₀], 222 (1) [C₁₆H₃₀⁺],

SCHINK ET AL.

397

194 (2) [C₁₄H₂₆⁺], 181 (2) [C₁₂¹³CH₂₄⁺], 180 (2)

[C₁₃H₂₄⁺], 166 (3) [C₁₂H₂₂⁺], 153 (3) [C₁₀¹³CH₂₀⁺],

152 (6) [C₁₁H₂₀⁺], 151 (3) [C₁₁H₁₉⁺], 139 (8) [C₉¹³CH₁₈⁺],

138 (12) [C₁₀H₁₈⁺], 137 (8) [C₁₀H₁₇⁺], 125 (17)

[C₈¹³CH₁₆⁺], 124 (22) [C₉H₁₆⁺], 123 (13) [C₉H₁₅⁺],

111 (18) [C₇¹³CH₁₄⁺], 97 (41) [C₆¹³CH₁₂⁺], 96 (65)

[C₇H₁₂⁺], 95 (48) [C₇H₁₁⁺], 82 (75) [C₆H₁₀⁺], 81 (100)

[C₆H₉⁺]; elemental analysis: calcd C 81.64, H 13.65,

found C 81.46, H 13.37.

the eluent. Products were obtained either as a colourless

oil (12a*: 550 mg, 94%) or as colourless solids (12b*:

644 mg, 94%; 12c*: 795 mg, 96%; 12d*: 900 mg, 84%).

4.7.1 | [1-¹³C]Pentadec-14-enyl acetate

(12a*)

¹H-NMR (500 MHz, CDCl₃, 298 K): δ (ppm) = 1.21–1.43

(m, 20 H, CH₃COO¹³CH₂CH₂(CH₂)₁₀CH₂CH═CH₂),

1.57–1.67 (m,

2

H, CH₃COO¹³CH₂CH₂), 2.00–2.09

4.6.4 | [1-¹³C]Hentricont-30-en-1-ol (11d*)

(m, 2 H, CH₂CH═CH₂), 2.05 (s, 3H, CH₃COO¹³CH₂),

4.06 (dt, ³J_CH2/CH2= 6.87 Hz, ¹J_13CH2/13C= 146.63 Hz,

2 H, CH₃COO¹³CH₂), 4.90–5.04 (m, 2 H, CH₂CH═CH₂),

m.p. 83–84^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.20–1.39 (m, 52 H, HO¹³CH₂CH₂(CH₂)₂₆

3

5.82 (ddt, J_CH/CH2[E]= 17.11 Hz, J_CH/CH2[Z]= 10.24 Hz,

CH₂CH═CH₂), 1.51–1.61 (m,

2

H, CH₂¹³CH₂OH),

³J_CH/CH2= 6.66 Hz, H, CH₂CH═CH₂); ¹³C-NMR

1

3

1.99–2.07 (m, 2 H, CH₂CH═CH₂), 3.63 (dt, J_CH2/

(126 MHz, CDCl₃, 298 K): δ (ppm) = 21.01 (CH₃), 25.90

(CH₃COO¹³CH₂CH₂CH₂), 28.58 (d, ¹J_13C/C= 38.63 Hz,

CH₃COO¹³CH₂CH₂), 28.93, 29.14 (2 ꢁ CH₂), 29.25

1

_CH2= 6.59 Hz, J_13CH2/13C= 140.90 Hz, 2 H, ¹³CH₂OH),

3

4.89–5.03 (m, 2 H, CH₂CH═CH₂), 5.81 (ddt, J_CH/CH2

_[E]= 16.61 Hz,

³J_CH/CH2[Z]= 10.31 Hz,

³J_CH/

(d,

³J_13C/C= 3.62 Hz,

CH₃COO¹³CH₂CH₂CH₂CH₂),

_CH2= 6.87 Hz, 1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz,

CDCl₃, 298 K): δ (ppm) = 25.69 (CH₂CH₂¹³CH₂OH),

28.90, 29.12 (2 ꢁ CH₂), 29.40 (d, ³J_13C/C= 3.62 Hz,

CH₂CH₂CH₂¹³CH₂OH), 29.47, 29.57, 29.66 (22 ꢁ CH₂),

32.68 (d, ¹J_13C/C= 37.42 Hz, CH₂¹³CH₂OH), 33.79

(CH₂CH═CH₂), 62.93 (¹³CH₂OH), 114.01 (CH₂CH═CH₂),

139.27 (CH₂CH═CH₂); IR (ATR): eν (cm^ꢂ1) = 3320

(m, OH), 3077 (w, ═CH₂), 2916 (s, CH₂), 2847 (s, CH₂),

1641 (m, C═C), 1462 (m, CH₂), 1045 (m, ¹³C─O),

991 (m, ─HC═CH₂), 912 (m, ─HC═CH₂), 720 (m, CH₂),

644 (m); elemental analysis: calcd C 82.63, H 13.83, found

C 82.28, H 13.42.

29.50, 29.54, 29.61 (6 ꢁ CH₂), 33.81 (CH₂CH═CH₂), 64.66

(CH₃COO¹³CH₂),

114.06 (CH₂CH═CH₂), 139.25

(CH₂CH═CH₂), 171.24 (CH₃COO¹³CH₂); IR (ATR): eν

(cm^ꢂ1) = 3077 (w, ═CH₂), 2922 (s, CH₂), 2853 (s, CH₂),

1742 (s, C═O), 1641 (m, C═C), 1464 (m, CH₂), 1364

(m, CH₂), 1233 (s, ═C─O), 1030 (s, ¹³C─O), 993 (m,

─HC═CH₂), 909 (m, ─HC═CH₂), 721 (m, CH₂), 633 (m),

606 (m); MS (EI): m/z (%) = 270 (1) [M⁺],

209 (1) [M⁺ꢂ C₂H₄O₂], 181 (1) [M⁺ꢂ C₂H₄O₂ꢂ C₂H₄],

180 (1) [M⁺ꢂ C₄H₈O₂], 166 (1) [M⁺ꢂ C₅H₁₀O₂],

152 (3) [C₁₁H₂₀⁺], 138 (3) [C₁₀H₁₈⁺], 125 (6) [C₈¹³CH₁₆⁺],

124 (8) [C₉H₁₆⁺], 123 (5) [C₉H₁₅⁺], 111 (6)

[C₇¹³CH₁₄⁺], 110 (11) [C₈H₁₄⁺], 109 (10) [C₈H₁₃⁺],

97

(18)

[C₆¹³CH₁₂⁺],

96

(34)

[C₇H₁₂⁺],

4.7 | Synthesis and characterization of

the ω-alkenylacetates 12a*–d* (modified

after Tashiro and Mori³⁶)

95 (36) [C₇H₁₁⁺], 82 (63) [C₆H₁₀⁺], 81 (100) [C₆H₉⁺];

elemental analysis: calcd C 76.15, H 11.97, found C 76.12,

H 11.89.

In a 25-ml round flask, 2.17 mmol of the corresponding

ω-alkenylalcohol (493-mg 11a*, 615-mg 11b*, 737-mg

11c*, 980-mg 11d*) were dissolved in 12 ml of pyridine.

After 1.23-ml (13.02 mmol) acetic anhydride were added

dropwise at 0^ꢀC, the reaction mixture was heated to 70^ꢀC

for another 3 h. After the reaction mixture reached room

temperature, it was poured into 60 ml of water and was

then extracted four times with 50 ml of diethylether each.

The combined organic phases were then washed with

diluted hydrochloric acid (1 M), a saturated solution of

NaHCO₃and brine. The organic phase was then dried

over Na₂SO₄and filtered, and the solvent was evaporated

under reduced pressure. Crude 12a*–d* were purified by

column chromatography using a mixture of ethyl acetate

and light petroleum (1:18 for 12a*–c*, 1:10 for 12d*) as

4.7.2 | [1-¹³C]Nonadec-18-enyl acetate

(12b*)

m.p. 29–30^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.21–1.43 (m, 28 H, CH₃COO¹³CH₂CH₂(CH₂)₁₄

CH₂CH═CH₂), 1.57–1.67 (m, 2 H, CH₃COO¹³CH₂CH₂),

2.00–2.10 (m,

2 H, CH₂CH═CH₂), 2.05 (s, 3H,

CH₃COO¹³CH₂),

4.06

(dt,

³J_CH2/CH2= 6.59 Hz,

¹J_13CH2/13C= 146.06 Hz, 2 H, CH₃COO¹³CH₂), 4.90–5.04

3

(m, 2 H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2[E]= 17.04,

³J_CH/CH2[Z]= 10.31,

³J_CH/CH2= 6.66 Hz,

1

H,

CH₂CH═CH₂); ¹³C-NMR (126 MHz, CDCl₃, 298 K): δ

(ppm) = 21.00 (CH₃), 25.90 (CH₃COO¹³CH₂CH₂CH₂),

1

28.58 (d, J_13C/C= 38.63 Hz, CH₃COO¹³CH₂CH₂), 28.94,

398

SCHINK ET AL.

3

29.14 (2 ꢁ CH₂), 29.25 (d, J_13C/C= 3.62 Hz, CH₃COO¹³

CH₂CH₂CH₂CH₂), 29.50, 29.55, 29.60, 29.66 (10 ꢁ CH₂),

33.81 (CH₂CH═CH₂), 64.66 (CH₃COO¹³CH₂), 114.05

elemental analysis: calcd C 78.94, H 12.68, found C 78.88,

H 12.32.

(CH₂CH═CH₂),

139.25

(CH₂CH═CH₂),

171.23

(CH₃COO¹³CH₂); IR (ATR): eν (cm^ꢂ1) = 3077 (w, ═CH₂),

2914 (s, CH₂), 2849 (s, CH₂), 1728 (s, C═O), 1641

(m, C═C), 1462 (m, CH₂), 1367 (m, CH₂), 1240 (s,

═C─O), 1030 (s, ¹³C─O), 993 (m, ─HC═CH₂),

910 (m, ─HC═CH₂), 718 (m, CH₂), 644 (m), 607 (m); MS

(EI): m/z (%) = 325 (1) [M⁺], 265 (4) [M⁺ꢂ C₂H₄O₂],

4.7.4 | [1-¹³C]Hentriacont-30-enyl acetate

(12d*)

m.p. 67–68^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.19–1.43 (m, 52 H, CH₃COO¹³CH₂CH₂

(CH₂)₂₆CH₂CH═CH₂), 1.57–1.67 (m, 2 H, CH₃COO¹³CH₂

CH₂), 2.01–2.10 (m, 2 H, CH₂CH═CH₂), 2.05 (s, 3H,

237 (2) [M⁺ꢂ C₂H₄O₂ꢂ C₂H₄], 222 (2) [M⁺ꢂ C₄

13

CH₁₀O₂], 208 (3) [M⁺ꢂ C₅¹³CH₁₂O₂], 194 (1) [M⁺ꢂ C₆

CH₃COO¹³CH₂),

4.06

(dt,

³J_CH2/CH2= 6.87 Hz,

13

CH₁₄O₂], 181 (2) [C₁₂¹³CH₂₄⁺], 180 (2) [C₁₃H₂₄⁺],

166 (3) [C₁₂H₂₂⁺], 152 (7) [C₁₁H₂₀⁺], 138 (13) [C₁₀H₁₈⁺],

125 (16) [C₈¹³CH₁₆⁺], 124 (16) [C₉H₁₆⁺], 110 (17)

[C₈H₁₄⁺], 96 (53) [C₇H₁₂⁺], 82 (68) [C₆H₁₀⁺], 81 (100)

[C₆H₉⁺]; elemental analysis: calcd C 77.79, H 12.39,

found C 77.59, H 12.04.

¹J_13CH2/13C= 146.06 Hz, 2 H, CH₃COO¹³CH₂), 4.90–5.04

3

(m, 2 H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2[E]= 17.04 Hz,

³J_CH/CH2[Z]= 10.17 Hz,

³J_CH/CH2= 6.44 Hz,

1

H,

CH₂CH═CH₂); ¹³C-NMR (126 MHz, CDCl₃, 298 K): δ

(ppm) = 21.01 (CH₃), 25.91 (CH₃COO¹³CH₂CH₂CH₂),

1

28.59 (d, J_13C/C= 38.63 Hz, CH₃COO¹³CH₂CH₂), 28.95,

29.16 (2 ꢁ CH₂), 29.26 (d, J_13C/C= 3.62 Hz, CH₃COO¹³

3

CH₂CH₂CH₂CH₂), 29.52, 29.57, 29.62, 29.70 (23 ꢁ CH₂),

33.83 (CH₂CH═CH₂), 64.67 (CH₃COO¹³CH₂), 114.06

(CH₂CH═CH₂), 139.27 (CH₂CH═CH₂), 171.24 (CH₃COO

CH₂); IR (ATR): eν (cm^ꢂ1) = 3077 (w, ═CH₂), 2914

(s, CH₂), 2847 (s, CH₂), 1738 (s, C═O), 1641 (m, C═C),

1462 (m, CH₂), 1367 (m, CH₂), 1242 (s, ═C─O), 1036

(s, ¹³C─O), 993 (m, ─HC═CH₂), 912 (m, ─HC═CH₂),

720 (m, CH₂), 642 (m), 606 (m); elemental analysis: calcd

C 80.46, H 13.06, found C 79.95, H 12.62.

4.7.3 | [1-¹³C]Tricos-22-enyl acetate (12c*)

m.p. 45–46^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.21–1.43 (m, 36 H, CH₃COO¹³CH₂CH₂(CH₂)₁₈

CH₂CH═CH₂), 1.57–1.67 (m, 2 H, CH₃COO¹³CH₂CH₂),

2.00–2.10 (m,

2 H, CH₂CH═CH₂), 2.05 (s, 3H,

CH₃COO¹³CH₂),

4.06

(dt,

³J_CH2/CH2= 6.87 Hz,

¹J_13CH2/13C= 146.63 Hz, 2 H, CH₃COO¹³CH₂), 4.90–5.04

3

(m,

2

H, CH₂CH═CH₂), 5.82 (ddt, J_CH/CH2[E]

=

16.90 Hz, ³J_CH/CH2[Z]= 10.31 Hz, ³J_CH/CH2= 6.73 Hz,

1 H, CH₂CH═CH₂); ¹³C-NMR (126 MHz, CDCl₃, 298 K):

δ (ppm) = 21.00 (CH₃), 25.90 (CH₃COO¹³CH₂CH₂CH₂),

4.8 | Synthesis and characterization of

the ω-acetoxycarboxylic acids 13a*–d*

(modified after Lee et al.³⁹)

28.58 (d, J_13C/C= 38.63 Hz, CH₃COO¹³CH₂CH₂), 28.94,

1

29.15

CH₃COO¹³CH₂CH₂CH₂CH₂), 29.51, 29.56, 29.61, 29.63,

29.68 (CH₂CH═CH₂), 64.66

(14 ꢁ CH₂), 33.81

(CH₃COO¹³CH₂),

114.05 (CH₂CH═CH₂), 139.25

(2 ꢁ CH₂),

29.25

(d,

³J_13C/C= 3.62 Hz,

In a 25-ml round flask were placed 6.3 ml of water,

which then were acidified with 0.75 ml of concentrated

sulfuric acid and 0.15 ml of glacial acetic acid. Then the

mixture was treated with 20 mg of the phase transfer cat-

alyst Adogen 464 and a solution of 1.12 mmol of the

corresponding ω-alkenylacetate (302-mg 12a*, 365-mg

12b*, 426-mg 12c*, 553-mg 12d*) in 6.3-ml dic-

hloromethane. While cooling with ice, 530-mg

(3.36 mmol) KMnO₄were added in portions over a

period of 3 h under vigorous stirring. Afterwards, the

reaction mixture was stirred at room temperature for

another 24 h before another portion of 89-mg

(0.56 mmol) KMnO₄was added followed by stirring the

mixture for additional 48 h at room temperature. After

the reaction time had expired, the now biphasic reaction

mixture was treated in portions with 428 mg

(4.12 mmol) of solid NaHSO₃, thus reducing excess

(CH₂CH═CH₂), 171.23 (CH₃COOCH₂); IR (ATR): eν

(cm^ꢂ1) = 3076 (w, ═CH₂), 2914 (s, CH₂), 2847 (s, CH₂),

1732 (s, C═O), 1642 (m, C═C), 1462 (m, CH₂), 1367

(m, CH₂), 1242 (s, ═C─O), 1034 (s, ¹³C─O),

991 (m, ─HC═CH₂), 912 (m, ─HC═CH₂), 720 (m, CH₂),

644 (m), 606 (m); MS (EI): m/z (%) = 354 (1) [M⁺],

321 (5) [M⁺ꢂ CH₄O], 293 (1) [M⁺ꢂ C₂H₄O₂],

278 (1) [M⁺ꢂ C₂¹³CH₆O₂], 264 (4) [M⁺ꢂ C₃¹³CH₈O₂],

251 (3) [M⁺ꢂ C₂H₄O₂ꢂ C₃H₆], 236 (3) [C₁₇H₃₂⁺],

223

(1)

[C₁₅¹³CH₃₀⁺],

222

(1)

[C₁₆H₃₀⁺],

208 (3) [C₁₅H₂₈⁺], 194 (2) [C₁₃H₂₄⁺], 180 (3) [C₁₃H₂₄⁺],

166 (3) [C₁₂H₂₂⁺], 152 (7) [C₁₁H₂₀⁺], 138 (21) [C₁₀H₁₈⁺],

124

(26)

[C₉H₁₆⁺],

110

(23)

[C₈H₁₄⁺],

96 (72) [C₇H₁₂⁺], 82 (8) [C₆H₁₀⁺], 81 (100) [C₆H₉⁺];

SCHINK ET AL.

399

KMnO₄and by that discolouring the system. In case of

the reaction of 12a*–c*, the mixture was then treated

with 50 ml of water and was subsequently extracted

four times with 50-ml dichloromethane each. The com-

bined organic phases were washed with water and

brine, dried over Na₂SO₄, filtered and evaporated under

reduced pressure. Purification of crude 13a*–c* was

achieved by column chromatography using a mixture of

diethylether and light petroleum (1:2) as the eluent and

yielding the pure products as colourless solids after

evaporation of the solvents (13a*: 226 mg, 75%; 13b*:

310 mg, 85%; 13c*: 351 mg, 82%). In case of the

reaction of 12d* following the addition of NaHSO₃dic-

hloromethane was evaporated under reduced pressure

and to the resulting aqueous phase was added another

portion of 150 ml of water leading to the precipitation

of the crude products, which were filtered, washed with

20 ml of water and dried under reduced pressure. The

resulting crude product 13d* was then recrystallized

from a mixture of light petroleum and ethyl acetate by

first suspending the compound in boiling light

petroleum before adding just the appropriate amount of

ethyl acetate to dissolve the compound. After standing

in the refrigerator overnight, 13d* was obtained as

colourless crystals, which were filtered, washed with

5 ml of cooled light petroleum and dried under reduced

pressure (13d*: 464 mg, 81%).

[C₇¹³CH₁₅⁺], 98 (93) [C₇H₁₄⁺], 83 (100) [C₆H₁₁⁺];

elemental analysis: calcd C 67.21, H 10.52, found C 67.13,

H 10.31.

4.8.2 | [18-¹³C]18-Acetoxyoctadecanoic acid

(13b*)

m.p. 71–73^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.21–1.40

CH₂CH₂(CH₂)₁₃CH₂CH₂COOH), 1.57–1.68 (m,

CH₃COO¹³CH₂CH₂, CH₂CH₂COOH), 2.05 (s, 3H,

CH₃COO¹³CH₂), 2.35 (t, ³J_CH2/CH2= 7.45 Hz,

H,

CH₂COOH), 4.06 (dt,

³J_CH2/CH2= 6.87 Hz,

(m,

26

H,

CH₃COO¹³

4

H,

2

¹J_13CH2/13C= 146.63 Hz, 2 H, CH₃COO¹³CH₂); ¹³C-NMR

(126 MHz, CDCl₃, 298 K): δ (ppm) = 21.00 (CH₃), 24.66

(CH₂CH₂COOH), 25.89 (CH₃COO¹³CH₂CH₂CH₂), 28.57

(d, ¹J_13C/C= 38.63 Hz, CH₃COO¹³CH₂CH₂), 29.04

(CH₂CH₂CH₂COOH), 29.24 (d, ³J_13C/C= 4.83 Hz,

CH₃COO¹³CH₂CH₂CH₂CH₂), 29.41, 29.50, 29.56, 29.61,

29.64

(10 ꢁ CH₂),

33.99

(CH₂COOH),

64.69

(CH₃COO¹³CH₂), 171.34 (CH₃COO), 179.76 (COOH); IR

(ATR): eν (cm^ꢂ1) = 3300–2500 (m, OH), 2914 (s, CH₂),

2847 (s, CH₂), 1728 (s, C═O_Ester), 1793 (s, C═O_Säure),

1462 (m, CH₂), 1427 (m, OH), 1367 (m, CH₂), 1246

(s, ═C─O_Ester), 1034 (s, ¹³C─O_Ester), 929 (m, OH),

720 (m, CH₂); elemental analysis: calcd C 70.22, H 11.15,

found C 70.14, H 10.88.

4.8.1 | [14-¹³C]14-Acetoxytetradecanoic acid

(13a*)

4.8.3 | [22-¹³C]22-Acetoxydocosanoic acid

(13c*)

m.p. 56–57^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.23–1.40 (m, 18 H, CH₃COO¹³CH₂CH₂(CH₂)₉

CH₂CH₂COOH), 1.57–1.68 (m, 4 H, CH₃COO¹³CH₂CH₂,

CH₂CH₂COOH), 2.05 (s, 3H, CH₃COO¹³CH₂), 2.35

m.p. 80–82^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.20–1.40

CH₂CH₂(CH₂)₁₇CH₂CH₂COOH), 1.57–1.68 (m,

CH₃COO¹³CH₂CH₂, CH₂CH₂COOH), 2.05 (s, 3H,

CH₃COO¹³CH₂), 2.35 (t, ³J_CH2/CH2= 7.45 Hz,

H,

CH₂COOH), 4.06 (dt,

³J_CH2/CH2= 6.87 Hz,

(m,

34

H,

CH₃COO¹³

4

H,

3

(t, J_CH2/CH2= 7.73 Hz, 2 H, CH₂COOH), 4.06 (dt, J_CH2/

1

_CH2= 6.87 Hz, J_13CH2/13C= 146.06 Hz, 2 H, CH₃COO¹³

2

CH₂); ¹³C-NMR (126 MHz, CDCl₃, 298 K): δ (ppm)

= 21.01 (CH₃), 24.66 (CH₂CH₂COOH), 25.88 (CH₃COO¹³

CH₂CH₂CH₂), 28.57 (d, ¹J_13C/C= 37.42 Hz, CH₃COO¹³

¹J_13CH2/13C= 146.63 Hz, 2 H, CH₃COO¹³CH₂); ¹³C-NMR

(126 MHz, CDCl₃, 298 K): δ (ppm) = 21.01 (CH₃), 24.67

(CH₂CH₂COOH), 25.89 (CH₃COO¹³CH₂CH₂CH₂), 28.57

(d, ¹J_13C/C= 38.63 Hz, CH₃COO¹³CH₂CH₂), 29.04

(CH₂CH₂CH₂COOH), 29.25 (d, ³J_13C/C= 4.83 Hz,

CH₃COO¹³CH₂CH₂CH₂CH₂), 29.42, 29.51, 29.55, 29.57,

29.63, 29.67 (14 ꢁ CH₂), 33.97 (CH₂COOH), 64.69

(CH₃COO¹³CH₂), 171.34 (CH₃COO), 179.63 (COOH); IR

(ATR): eν (cm^ꢂ1) = 3300–2500 (m, OH), 2914 (s, CH₂),

2847 (s, CH₂), 1730 (s, C═O_Ester), 1797 (s, C═O_Säure),

1462 (m, CH₂), 1429 (m, OH), 1371 (m, CH₂), 1252

(s, ═C─O_Ester), 1035 (s, ¹³C─O_Ester), 944 (m, OH),

720 (m, CH₂); elemental analysis: calcd C 72.38, H 11.60,

found C 72.00, H 11.23.

3

CH₂CH₂), 29.03 (CH₂CH₂CH₂COOH), 29.23 (d, J_13C/

_C= 3.62 Hz, CH₃COO¹³CH₂CH₂CH₂CH₂), 29.39, 29.48,

29.52, 29.55 (6 ꢁ CH₂), 33.98 (CH₂COOH), 64.69

(CH₃COO¹³CH₂), 171.35 (CH₃COO), 179.74 (COOH); IR

(ATR): eν (cm^ꢂ1) = 3300–2500 (m, OH), 2914 (s, CH₂),

2847 (s, CH₂), 1728 (s, C═O_Ester), 1697 (s, C═O_Säure),

1464 (m, CH₂), 1429 (m, OH), 1372 (m, CH₂), 1248

(s, ═C─O_Ester), 1034 (s, ¹³C─O_Ester), 937 (m, OH),

721 (m, CH₂); MS (EI): m/z (%) = 287 (1) [M⁺], 227 (10)

[M⁺ꢂ C₂H₄O₂], 209 (6) [M⁺ꢂ C₂H₄O₂ꢂ H₂O], 180 (3)

[C₁₂¹³CH₂₃⁺], 166 (8) [C₁₁¹³CH₂₁⁺], 152 (8)

[C₁₀¹³CH₁₉⁺], 138 (8) [C₉¹³CH₁₇⁺], 112 (30)

400

SCHINK ET AL.

4.8.4 | [30-¹³C]30-Acetoxytriacontanoic acid

(13d*)

product compounds (14a*: 90 mg, 89%; 14b*: 115 mg,

93%; 14c*: 133 mg, 91%; 14d*: 119 mg, 62%).

m.p. 94–95^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.20–1.39

CH₂CH₂(CH₂)₁₇CH₂CH₂COOH), 1.55–1.66 (m,

CH₃COO¹³CH₂CH₂, CH₂CH₂COOH), 2.03 (s, 3H,

CH₃COO¹³CH₂), 2.31 (t, ³J_CH2/CH2= 7.73 Hz,

H,

CH₂COOH), 4.04 (dt,

³J_CH2/CH2= 6.87 Hz,

¹J_13CH2/13C= 146.06 Hz, 2 H, CH₃COO¹³CH₂); ¹³C-NMR

(126 MHz, CDCl₃/MEOD, 298 K): (ppm) = 20.94

(CH₃), 24.75 (CH₂CH₂COOH), 25.85 (CH₃COO¹³

CH₂CH₂CH₂), 28.52 (d,

¹J_13C/C= 37.42 Hz,

CH₃COO¹³CH₂CH₂), 29.06 (CH₂CH₂CH₂COOH), 29.21

(d,

³J_13C/C= 3.62 Hz, CH₃COO¹³CH₂CH₂CH₂CH₂),

(m,

34

H,

CH₃COO¹³

4.9.1 | [14-¹³C]14-Hydroxytetradecanoic acid

(14a*)

4

H,

2

m.p. 91–92^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ (ppm)

= 1.20–1.39 (m, 18 H, HO¹³CH₂CH₂(CH₂)₉CH₂CH₂COOH),

1.50–1.67 (m, 4 H, CH₂CH₂COOH, CH₂CH₂¹³OH), 2.33

3

δ

(t, J_CH2/CH2= 7.73 Hz, 2 H, CH₂COOH), 3.63 (dt, J_CH2/

_CH2= 6.87 Hz, ¹J_13CH2/13C= 140.90 Hz, 2 H, CH₂¹³OH);

¹³C-NMR (151 MHz, CDCl₃, 298 K): δ (ppm) = 24.68

(CH₂CH₂COOH),

25.69

(CH₂CH₂¹³CH₂OH),

28.99

(CH₂CH₂CH₂COOH), 29.14, 29.32, 29.36, 29.44, 29.47

(7 ꢁ CH₂), 32.71 (d, ¹J_13C/C= 36.22 Hz, CH₂¹³CH₂OH),

33.88 (CH₂COOH), 63.08 (¹³CH₂OH), 178.88 (CH₂COOH);

IR (ATR): eν (cm^ꢂ1) = 3500–2500 (m, OH), 2913 (s, CH₂),

2847 (s, CH₂), 1682 (m, C═O), 1470 (s, CH₂), 1410

(w, OH), 1306 (m, CH₂), 1020 (m, ¹³C─O), 718 (m, CH₂),

529 (w); elemental analysis: calcd C 68.94, H 11.50, found

C 68.91, H 11.08.

29.41, 29.47, 29.52, 29.55, 29.65 (22 ꢁ CH₂), 33.91

(CH₂COOH), 64.72 (CH₃COO¹³CH₂), 171.47 (CH₃COO),

177.92 (COOH); IR (ATR): eν (cm^ꢂ1) = 3300–2500

(m, OH), 2914 (s, CH₂), 2847 (s, CH₂), 1732 (s, C═O_Ester),

1697 (s, C═O_Säure), 1462 (m, CH₂), 1429 (m, OH), 1370

(m, CH₂), 1244 (s, ═C─O_Ester), 1034 (s, ¹³C─O_Ester),

949 (m, OH), 720 (m, CH₂); elemental analysis: calcd C

75.29, H 12.21, found C 74.84, H 11.89.

4.9.2 | [18-¹³C]18-Hydroxyoctadecanoic acid

(14b*)

4.9 | Synthesis and characterization of

the ω-hydroxycarboxylic acids 14a*–d*

(modified after Tori et al.⁴⁰)

m.p. 97–99^ꢀC; ¹H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.22–1.40 (m, 26 H, HO¹³CH₂CH₂(CH₂)₁₃

CH₂CH₂COOH), 1.53–1.68 (m, 4 H, CH₂CH₂COOH,

In a 100-ml round flask were placed 0.41 mmol of the

corresponding ω-acetoxycarboxylic acid (118-mg 13a*,

141-mg 13b*, 164-mg 13c*, 210-mg 13d*), which were

then treated with a solution of 4.5-g NaOH in 100 ml of

methanol. The reaction mixture was then stirred for

5 days at room temperature (in case of the reaction of

13d*, 7.5-g NaOH were used and stirring was performed

for 7 days). After the reaction time had expired, the

mixture was poured into 200 ml of water and was then

acidified by half concentrated hydrochloric acid leading

to the precipitation of a colourless solid. This suspension

was then stirred for 2 h at room temperature. Then the

solution was filtered, and the precipitate washed with

50 ml of water and dried under reduced pressure over-

night. For purification, the crude products were treated

with an excess of hot ethyl acetate and filtered using a G3

frit, which was then washed twice with an additional por-

tion of hot ethyl acetate. The combined organic solutions

were then reduced to approximately one third of the orig-

inal volume and was then treated with light petroleum.

This solution was allowed to stand in the refrigerator

overnight. The resulting crystals were filtered, washed

with 3-ml cooled light petroleum and dried under

reduced pressure yielding colourless crystals of the

CH₂CH₂¹³OH), 2.35 (t, ³J_CH2/CH2= 7.45 Hz,

2

H,

³J_CH2/CH2= 6.59 Hz,

H, CH₂¹³OH); ¹³C-NMR

298 K): (ppm) = 26.03

CH₂COOH),

¹J_13CH2/13C= 141.48 Hz,

(151 MHz, THF,

3.65

(dt,

2

δ

(CH₂CH₂COOH), 27.11 (CH₂CH₂¹³CH₂OH), 30.31

(CH₂CH₂CH₂COOH), 30.52, 30.66, 30.72, 30.76, 30.82,

30.87 (11 ꢁ CH₂), 34.27 (d, ¹J_13C/C= 38.63 Hz,

CH₂¹³CH₂OH), 34.44 (CH₂COOH), 62.72 (¹³CH₂OH),

174.66 (CH₂COOH); IR (ATR): eν (cm^ꢂ1) = 3500–2500

(m, OH), 2914 (s, CH₂), 2849 (s, CH₂), 1705 (m, C═O),

1470 (s, CH₂), 1412 (w, OH), 1294 (m, CH₂), 1042 (m,

¹³C─O), 718 (m, CH₂), 528 (w); elemental analysis: calcd

C 72.04, H 12.04, found C 71.60, H 11.80.

4.9.3 | [22-¹³C]22-Hydroxydocosanoic acid

(14c*)

1

m.p. 107–108^ꢀC; H-NMR (500 MHz, CDCl₃, 298 K): δ

(ppm) = 1.20–1.41 (m, 34 H, HO¹³CH₂CH₂(CH₂)₁₇CH₂

CH₂COOH), 1.53–1.68 (m, 4 H, CH₂CH₂COOH, CH₂

CH₂¹³OH), 2.36 (t, ³J_CH2/CH2= 7.45 Hz, 2 H, CH₂COOH),

3.65 (dt, ³J_CH2/CH2= 6.59 Hz, ¹J_13CH2/13C= 140.90 Hz,

SCHINK ET AL.

401

2 H, CH₂¹³OH); ¹³C-NMR (151 MHz, THF, 298 K): δ

(ppm) = 26.04 (CH₂CH₂COOH), 27.11 (CH₂CH₂¹³CH₂

OH), 30.31 (CH₂CH₂CH₂COOH), 30.52, 30.67, 30.72,

ORCID

Wolfgang Imhof https://orcid.org/0000-0003-0954-5464

1

30.77, 30.82, 30.87 (15 ꢁ CH₂), 34.27 (d, J_13C/

REFERENCES

_C= 38.63 Hz, CH₂¹³CH₂OH), 34.44 (CH₂COOH), 62.72

1. Pollard M, Beisson F, Li Y, Ohlrogge JB. Building lipid barriers:

biosynthesis of cutin and suberin. Trends Plant Sci. 2008;13(5):

236-246.

2. Cheynier V, Comte G, Davies KM, Lattanzio V, Martens S.

Plant phenolics: recent advances on their biosynthesis, genet-

ics, and ecophysiology. Plant Physiol Biochem. 2013;72:1-20.

3. Isaacson T, Kosma DK, Matas AJ, et al. Cutin deficiency in the

tomato fruit cuticle consistently affects resistance to microbial

infection and biomechanical properties, but not transpirational

water loss. Plant J. 2009;60(2):363-377.

(¹³CH₂OH), 174.66 (CH₂COOH); IR (ATR): eν (cm^ꢂ1

)

= 3500–2500 (m, OH), 2913 (s, CH₂), 2847 (s, CH₂), 1697

(m, C═O), 1471 (s, CH₂), 1411 (w, OH), 1298 (m, CH₂),

1041 (m, ¹³C─O), 717 (m, CH₂), 533 (w); elemental analy-

sis: calcd C 74.17, H 12.40, found C 73.60, H 12.08.

4.9.4 | [30-¹³C]30-Hydroxytricontanoic acid

4. Kissinger M, Tuvia-Alkalai S, Shalom Y, et al. Characterization

of physiological and biochemical factors with postharvest water

loss in ripe pepper fruit during storage. J Am Soc Hort Sci.

2005;130(5):735-741.

5. Leide J, Hildebrandt U, Reussing K, Riederer M, Vogg G. The

developmental pattern of tomato fruit wax accumulation and

its impact on cuticular transpiration barrier properties: effects

of a deficiency in a β-ketoacyl-coenzyme A synthase (LeCER6).

Plant Physiol. 2007;144(3):1667-1679.

(14d*)

1

m.p. 105–108^ꢀC; H-NMR (500 MHz, DMSO, 373 K): δ

(ppm) = 1.20–1.35 (m, 34 H, HO¹³CH₂CH₂(CH₂)₁₇

CH₂CH₂COOH), 1.39–1.57 (m, 4 H, CH₂CH₂COOH,

CH₂CH₂¹³OH), 2.19 (t, ³J_CH2/CH2= 7.45 Hz,

2

H,

=

3

1

CH₂COOH), 3.40 (dt, J_CH2/CH2= 6.30 Hz, J_13CH2/13C

138.04 Hz, 2 H, CH₂¹³OH); ¹³C-NMR (151 MHz, THF,

6. Franke R, Schreiber L. Suberin—a biopolyester forming apo-

plastic plant interfaces. Curr Opin Plant Biol. 2007;10(3):252-259.

7. Kolattukudy PE. Polyesters in higher plants. In: Scheper T,

Babel W, Blanch HW, et al., eds. Advances in Biochemical Engine-

ering/Biotechnology. Berlin Heidelberg: Springer; 2001:1-49.

8. Bernards MA. Demystifying suberin. Can J Bot. 2002;80(3):

227-240.

9. Ranathunge K, Schreiber L, Franke R. Suberin research in the

genomics era—new interest for an old polymer. Plant Sci.

2011;180(3):399-413.

298 K):

δ

(ppm) = 24.13 (CH₂CH₂COOH), 27.11

(CH₂CH₂¹³CH₂OH), 28.17 (CH₂CH₂CH₂COOH), 28.28,

28.53, 28.65 (23 ꢁ CH₂), 32.17 (d, ¹J_13C/C= 37.42 Hz,

CH₂¹³CH₂OH), 33.37 (CH₂COOH), 60.47 (¹³CH₂OH),

173.74 (CH₂COOH); IR (ATR): eν (cm^ꢂ1) = 3500–2500

(m, OH), 2913 (s, CH₂), 2847 (s, CH₂), 1703 (m, C═O),

1472 (s, CH₂), 1411 (w, OH), 1274 (m, CH₂), 1037

(m, ¹³C─O), 716 (m, CH₂), 532 (w); elemental analysis:

calcd C 76.91, H 12.87, found C 76.40, H 12.48.

10. Franke R, Dombrink I, Schreiber L. Suberin goes genomics:

use of a short living plant to investigate a long lasting polymer.

Front Plant Sci. 2012;3:1-8.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge elemental analyses

being performed at the Institute of Chemistry and Bioen-

gineering at Technical University Ilmenau, Germany.

The research has been funded by the research fund of the

University Koblenz - Landau.

11. Beisson F, Li-Beisson Y, Pollard M. Solving the puzzles of cutin

and suberin polymer biosynthesis. Curr Opin Plant Biol. 2012;

15(3):329-337.

12. Fich EA, Segerson NA, Rose JKC. The plant polyester cutin:

biosynthesis, structure, and biological roles. Annu Rev Plant

Biol. 2016;67(1):207-233.

Open Access funding enabled and organized by

Projekt DEAL.

13. Vishwanath SJ, Delude C, Domergue F, Rowland O. Suberin:

biosynthesis, regulation, and polymer assembly of a protective

extracellular barrier. Plant Cell Rep. 2015;34(4):573-586.

14. Schreiber L. Transport barriers made of cutin, suberin and

associated waxes. Trends Plant Sci. 2010;15(10):546-553.

15. Enstone DE, Peterson CA, Ma F. Root endodermis and exoder-

mis: structure, function, and responses to the environment.

J Plant Growth Regul. 2002;21(4):335-351.

16. Holloway PJ. Structure and histochemistry of plant cuticular

membranes. In: Cutler DF, Alvin KL, Price CE, eds. The Plant

Cuticle. London: Academic; 1982:45-85.

17. Graça J, Schreiber L, Rodrigues J, Pereira H. Glycerol and glyc-

eryl esters of omega-hydroxyacids in cutins. Phytochemistry.

2002;61(2):205-215.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available

from the corresponding author upon reasonable request.

Supporting information contains synthetic procedures

and analytical data for compounds 2e–h, 4a–g, 5a–d,

6a–d, 7a–d, 8a–d, 9a–d, 10a–d, 11a–d, 12a–d, 13a–d and

14a–c as well as ¹H- and ¹³C-NMR spectra of compounds

2e–h, 4a–g, 5a–d, 6a–d, 7a–d, 8a–d, 9a–d, 10a–d, 11a–d,

12a–d, 13a–d and 14a–c. All compounds except 2e–h,

4a–g, 5a–d and 6a–d were synthesized with and without

a label. Compounds with a ¹³C label are marked with an

asterisk (*). In addition, investigations on the isotopic

purity of K¹³CN starting material are available.²⁶

18. Graça J, Pereira H. Suberin structure in potato periderm:

glycerol, long-chain monomers, and glyceryl and feruloyl

dimers. J Agric Food Chem. 2000;48(11):5476-5483.

402

SCHINK ET AL.

19. Graça J, Santos S. Glycerol-derived ester oligomers from cork

suberin. Chem Phys Lipids. 2006;144(1):96-107.

20. Lavrieux M, Breheret JG, Disnar JR, Jacob J, Le Milbeau C,

Zocatelli R. Preservation of an ancient grassland biomarker

signature in a forest soil from the French Massif Central. Org

Geochem. 2012;51:1-10.

21. Lichtfouse E, Leblond C, Da Silva M, Behar F. Occurrence of

biomarkers and straight-chain biopolymers in humin: implica-

tion for the origin of soil organic matter. Naturwissenschaften.

1998;85(10):497-501.

22. Lichtfouse E, Chenu C, Baudin F, et al. A novel pathway of soil

organic matter formation by selective preservation of resistant

straight-chain biopolymers: chemical and isotope evidence. Org

Geochem. 1998;28(6):411-415.

23. Jandl G, Leinweber P, Schulten HR, Ekschmitt K. Contribution

of primary organic matter to the fatty acid pool in agricultural

soils. Soil Biol Biochem. 2005;37(6):1033-1041.

24. Dennis M, Kolattukudy PE. A cobalt-porphyrin enzyme con-

verts a fatty aldehyde to a hydrocarbon and CO. Proc Natl Acad

Sci U S A. 1992;89(12):5306-5310.

25. Rhead MM, Eglinton G, Draffan GH, England PJ. Conversion

of oleic acid to saturated fatty acids in Severn Estuary sedi-

ments. Nature. 1971;232(5309):327-330.

34. Nacsa ED, Lambert TH. Cyclopropenone catalyzed substitution

of alcohols with mesylate ion. Org Lett. 2013;15(1):38-41.

35. Latscha HP, Kazmaier U, Klein HA. Organische Chemie. Berlin,

Heidelberg: Springer Spektrum; 2016.

36. Tashiro T, Mori K. Synthesis of sphingolipids with an

ω-esterified long acyl chain, ceramide components of the

human epidermis. Biosci Biotechnol Biochem. 2012;76(9):

1715-1720.

37. Zimmermann F, Meux E, Mieloszynski J-L, Lecuire J-M,

Oget N. Ruthenium catalysed oxidation without CCl₄of oleic

acid, other monoenic fatty acids and alkenes. Tetrahedron Lett.

2005;46(18):3201-3203.

38. Travis BR, Narayan RS, Borhan B. Osmiumtetroxide-promoted

catalytic oxidative cleavage of olefins: an organometallic

ozonolysis. J Am Chem Soc. 2002;124(15):3824-3825.

39. Lee DG, Lamb SE, Chang VS. Carboxylic acids from the oxida-

tion of terminal alkenes by permanganate: nonadecanoic acid.

Org Synth. 1981;60:11-14.

40. Tori M, Sono M, Asakawa Y. Hydroxylation of aliphatic

compounds with m-chloroperbenzoic acid. Synthesis of

hydroxylated vitamin K analogues. Bull Chem Soc Jpn. 1985;58

(9):2669-2672.

ꢀ

41. Rosillo M, Arnaiz E, Abdi D, Blanco-Urgoiti J, Domínguez G,

26. Schink C, Spielvogel S, Imhof W. Synthesis and characteriza-

tion of ¹³C-labelled dicarboxylic acids of the general formula

HO₂¹³C-(CH₂)_n-¹³CO₂H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26,

28). J Label Compd Radiopharm. 2021;64(1):14-29.

27. Takano Y, Chikaraishi Y, Ogawa NO, et al. Sedimentary mem-

brane lipids recycled by deep-sea benthic archaea. Nat Geosci.

2010;3(12):858-861.

28. Tortajada A, Duan Y, Sahoo B, et al. Catalytic dec-

arboxylation/carboxylation platform for accessing isotopically

labeled carboxylic acids. ACS Catal. 2019;9(7):5897-5901.

29. Gauthier DR Jr, Rivera NR, Yang H, Schultz DM, Shultz CS.

Palladium-catalyzed carbon isotope exchange on aliphatic and

Pérez-Castells J. Combination of RCM and the Pauson-Khand

reaction: one-step synthesis of tricyclic structures. Eur J Org

Chem. 2008;2008(23):3917-3927.

42. Coxon GD, Al Dulayymi J'aR, Morehouse C, et al. Synthesis

and properties of methyl 5-(1⁰R,2⁰S)-(2-octadecylcycloprop-1-yl)

pentanoate and other ω-19 chiral cyclopropane fatty acids and

esters related to mycobacterial mycolic acids. Chem Phys Lipids.

2004;127(1):35-46.

43. Franchini L, Panza L, Kongmanas K, Tanphaichitr N,

Faull KF, Ronchetti F. An efficient and convenient synthesis of

deuterium-labelled seminolipid isotopomers and their ESI-MS

characterization. Chem Phys Lipids. 2008;152(2):78-85.

benzoic acid chlorides.

15596-15600.

30. Kingston C, Wallace MA, Allentoff AJ, et al. Direct carbon

isotope exchange through decarboxylative carboxylation. J Am

Chem Soc. 2019;141(2):774-779.

31. Drescher S, Meister A, Blume A, Karlsson G, Almgren M,

Dobner B. General synthesis and aggregation behaviour of a

series of single-chain 1,ω-bis (phosphocholines). Chem A Eur J.

2007;13(18):5300-5307.

32. Zweifel G, Nagase K, Brown HC. Hydroboration. XIII. The

hydroboration of dienes with disiamylborane. A convenient

procedure for the conversion of selected dienes into unsatu-

rated alcohols. J Am Chem Soc. 1962;84(2):190-195.

33. Jiménez T, Barea E, Oltra JE, Cuerva JM, Justicia J. Mn(0)-

mediated chemoselective reduction of aldehydes. Application

to the synthesis of α-deuterioalcohols. J Org Chem. 2010;75(20):

7022-7025.

J Am Chem Soc. 2018;140(46):

SUPPORTING INFORMATION

Additional supporting information may be found online

in the Supporting Information section at the end of this

article.

How to cite this article: Schink C, Spielvogel S,

Imhof W. Synthesis of ¹³C-labelled ω-hydroxy

carboxylic acids of the general formula

HO₂¹³C-(CH₂)_n-CH₂OH or HO₂C-(CH₂)_n-¹³CH₂OH

(n = 12, 16, 20, 28). J Label Compd Radiopharm.

2021;64:385–402. https://doi.org/10.1002/jlcr.3931

Article Doi

Synthesis of 13C-labelled ω-hydroxy carboxylic acids of the general formula HO213C-(CH2)n-CH2OH or HO2C-(CH2)n-13CH2OH (n = 12, 16, 20, 28)

DOI: 10.1002/jlcr.3931

Source and publish data:

Authors:

Article abstract of DOI:10.1002/jlcr.3931

Full text of DOI:10.1002/jlcr.3931

Products guided by the article

R&D Labs maybe for 338389-27-8

Relevant to this article

Hot Product