Synthesis of halogenated 1-O-alkylglycerols from ricinoleic acid derivatives

Article abstract of DOI:10.1080/00397911.2020.1750034

Resistance to the existing drugs and increasing numbers of diseases result in identifying new drug candidates with new forms of activity. As marine organisms are well known to provide a wide range of original compounds, Herein, we report the synthesis of new non-natural brominated, iodinated and chlorinated-substituted 1-O-alkylglycerols 5–7, analogs of a prominent 1-O-alkylglycerol (AKG) of the natural shark liver oil (SLO) mixture, namely the AKGs 18:1, n-9.

Full text of DOI:10.1080/00397911.2020.1750034

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
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Synthesis of halogenated 1-O-alkylglycerols from
ricinoleic acid derivatives
René Pemha, Dieudonné Emmanuel Pegnyemb & Paul Mosset
To cite this article: René Pemha, Dieudonné Emmanuel Pegnyemb & Paul Mosset (2020):
Synthesis of halogenated 1-O-alkylglycerols from ricinoleic acid derivatives, Synthetic
Communications, DOI: 10.1080/00397911.2020.1750034
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https://doi.org/10.1080/00397911.2020.1750034
Synthesis of halogenated 1-O-alkylglycerols from ricinoleic
acid derivatives
a,b
c
d
ꢀ
ꢀ
, Dieudonne Emmanuel Pegnyemb , and Paul Mosset
Rene Pemha
a
ꢀ
ꢀ
Universite de Rennes, Ecole Nationale Superieure de Chimie de Rennes, CNRS, UMR 6226, Rennes,
b
France; AGIR, EA 4294, UFR of Pharmacy, Jules Verne University of Picardie, Amiens, France;
c
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Departement de Chimie Organique, Faculte des Sciences, Universite de Yaounde I, Yaounde,
d
ꢀ
Cameroun; Universite de Rennes, CNRS, ISCR, UMR 6226, Rennes, France
ABSTRACT
ARTICLE HISTORY
Received 27 February 2020
Resistance to the existing drugs and increasing numbers of diseases
result in identifying new drug candidates with new forms of activity.
As marine organisms are well known to provide a wide range of
original compounds, Herein, we report the synthesis of new non-nat-
ural brominated, iodinated and chlorinated-substituted 1-O-alkylgly-
cerols 5–7, analogs of a prominent 1-O-alkylglycerol (AKG) of the
natural shark liver oil (SLO) mixture, namely the AKGs 18:1, n-9.
KEYWORDS
Alkylglycerol (AKG); fatty
acids; halogenated
compounds; lipids; marine
natural products
GRAPHICAL ABSTRACT
Introduction
Marine algae produce a cocktail of halogenated metabolites with potential commercial
value. Structures exhibited by these compounds go from acyclic entities with a linear
chain to complex polycyclic molecules. In the last decade, their medical and pharma-
ceutical application were investigated.[1] Bromide is more frequently used by algae for
organohalogen production, although chlorine occurs in higher concentrations than
bromine in seawater. The prevalence of halogens is not similar in marine algae: chlorine
ꢀ
ꢀ ꢀ
Universite de Rennes, Ecole Nationale Superieure de Chimie de
CONTACT Rene Pemha
pemharene@gmail.com
ꢀ
Rennes, CNRS, UMR 6226, 11 allee de Bealieu, 35708 Rennes, France; AGIR, EA 4294, UFR of Pharmacy, Jules Verne
University of Picardie, 80037 Amiens, France.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

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R. PEMHA ET AL.
Figure 1. Synthesized AKGs 1–4 from ricinoleic acid.
and bromine appear to be the main halogens used to increase biological activity of sec-
ondary metabolites, whereas iodine and fluorine remain quite unusual within the chem-
ical structures.[2]
Natural 1-O-alkylglycerols (AKGs) are bioactive ether lipids present in body cells and flu-
ids. They are precursors of ether phospholipids participating in structures and functions of
membranes in certain cells such as white blood cells or macrophages. AKGs are also found
in bone marrow lipids and milk.[3] Marine sources of AKGs such as the liver oil of certain
shark species or ratfish (elasmobranch fishes) contain high levels of these compounds as a
mixture of few species varying by length and unsaturation or saturation of the alkyl chain.
The composition of AKGs in the shark liver oil (SLO) mixture is as follows: 12:0, 1–2%;
14:0, 1–3%; 16:0, 9–13%; 16:1 n-7, 11–13%; 18:0, 1–5%; 18:1 n-9, 54–68%; 18:1 n-7, 4–6%;
and minor species (<1%). They have multiple biological activities such as hematopoiesis
stimulation,[4] lowering radiotherapy-induced injuries,[5] reducing tumor growth[6] and
improving vaccination efficiency.[7,8]
Currently, resistance to the existing drugs and increasing numbers of diseases result
in identifying new drug candidates with new forms of activities. Thus, synthesized non-
natural halogenated AKGs derivatives of natural fatty acids could be one new source of
drug delivery systems. Additionally, defined synthetic routes for these targets will facili-
tate further investigation of biological activities, as natural AKGs were found present in
various human cells but only in trace quantities. Likewise, in contrast to brominated
and chlorinated metabolites, iodinated and fluorinated compounds are quite rare.[9]
Non-natural synthesized AKGs 1–4 display antimicrobial activity to different extents
alone, and some beneficial synergistic effects were also observed when AKG 1 was com-
bined with gentamicin, and when AKG 3 was combined with ciprofloxacin and ampicil-
lin.[10] However, despite known biological activities of compounds containing a
difluoromethylene group or fluorine atoms,[11,12] AKG 4 exhibited less antimicrobial
activity than other AKGs 1–3.[10] This slightly antimicrobial activity observed for com-
pound 4 may be due to the lack of a second asymmetric center at the 12 position in the
alkyl chain, or the presence of the fluorine atoms in its structure (Figure 1).
Biological properties of halogenated compounds were researched in the past decades,
resulting in antibacterial, antifungal, antiviral, anti-inflammatory, antiproliferative, anti-
fouling, antifeedant, cytotoxic, ichthyotoxic, and insecticidal activities.[13–15] Taking into
account halogenated compounds, natural and non-natural alkylglycerols’ beneficial
effects, herein, we report the synthesis of new non-natural brominated, iodinated and
chlorinated-substituted 1-O-alkylglycerols 5–7, analogs of a prominent AKG of the nat-
ural shark liver oil (SLO) mixture, namely the AKG 18:1, n-9 (Figure 2).

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Figure 2. Non-natural synthesized halogenated 1-O-alkylglycerols (AKGs) 5–7.
Results and discussion
Among known natural fatty acids, ricinoleic acid (RA) is one of the major fatty acids
occurring in castor oil (almost 90%).[16] Such a high concentration of this unusual
unsaturated fatty acid may be responsible for castor oil’s remarkable healing abilities. It
is known to be effective in preventing the growth of numerous species of viruses, bac-
teria, yeasts, and molds.[17,18] Due to the many beneficial effects of this fatty acid com-
ponent, the use of castor oil can be applied topically to treat a wide variety of health
complaints,[19] and it also has pharmacological effects on the human gastrointes-
tinal tract.[20]
Therefore, AKGs 5–7 were designed as analogs of a prominent AKG of the natural
shark liver oil (SLO) mixture, namely the AKG 18:1, n-9, with the same alkyl chain
length C18 and D9 unsaturation which are both favorable for the biological activity,[10,21]
but with either a bromine, iodine or chlorine atom at the position 12 in the alkyl chain.
The preparation of AKGs 5–7 required a protection–deprotection sequence to yield the
penultimate intermediate 17. The synthesis of 5–7 began with the esterification of RA 8
into methyl ricinoleate 9 in 75% yield using boron trifluoride in methanol, along with
4% of a by-product (dimer) 10, arising from a subsequent esterification of the secondary
alcohol of 9 formed with RA.[22] Compound 10 gave spectroscopic properties (1H and
13C NMR, as well as correlation spectra) in full agreement with its structure. This was
confirmed by HRMS (ESI, m/z) showing 615.4971 for [M þ Na]þ (Scheme 1). Although
it is not strictly necessary, the process could be improved by converting this very minor
by-product 10 into 9 by transesterification and thus eliminating it by a subsequent
treatment of 10 containing 9 by potassium carbonate in methanol.
The hydroxyl group protection of 9 with a chlorotriisopropylsilane in the presence of
imidazole as a base in DMF provided 11 in 61% yield.[23] Afterward, 11 was reduced to
the alcohol 12 in 75% yield using Red-Al in diethyl ether (Scheme 1). Compound 12
upon mesylation conditions using mesyl chloride in DCM and Et3N provided 13 in
76% yield, which was in turn alkylated under anhydrous conditions with 2,3-isopropyli-
dene-sn-glycerol 14 in DMF in the presence of sodium hydride to provide acetonide 15
in 68% yield. Following this, silyl ether group was removed using TBAF in THF at
room temperature to provide 16 in 92% yield, which under mesylation conditions using
mesylchloride in DCM and Et3N, yielded 17 in 59% yield (Scheme 1).
17 under substitution of the mesylate intermediate group by SN2 substitution reaction
using consecutively benzyltriethylammonium chloride in DMF provided 18 in 81%

4
R. PEMHA ET AL.
Scheme 1. Synthesis of the penultimate intermediate 17. Reagents and conditions: (a) BF3ꢁ2MeOH,
MeOH, 50 ꢀC, 15 h, 75% of 9 and 4% of 10; (b) K2CO3, MeOH, rt, 42 h, quantitative conversion of 10
into 9; (c) ClSii-Pr3, imidazole, DMF, 48 h, rt, 61%; (d) Red-Al, Et2O, 0 ꢀC, 5 h, 94%; (e) MsCl, Et3N, DCM,
ꢂ50 ꢀC, 2 h, 76%; (f) NaH, DMF, 15 h, rt, 68%; (g) TBAF, THF, rt, 20 h, 92%; (h) MsCl, Et3N, DCM,
ꢂ50 ꢀC, 4 h, 59%.
yield, lithium bromide in acetonitrile gave 19 in 60% and sodium iodide in acetone pro-
vided 20 in 59% yield. Easy acetonide 18–20 cleavage under acid conditions (p-toluene-
sulfonic acid monohydrate in MeOH/H2O (9:1)) provided AKG 5 in 69% yield, AKG 6
in 89% yield and AKG 7 in 74% yield (Scheme 2). Supplementary materials of all syn-
thetic compounds for this sequence are attached in a file as figure S1.1–S1.28.
Experimental section
Generalities
Moisture sensitive reactions were performed under nitrogen. Anhydrous tetrahydrofuran
(THF) and diethyl ether (Et2O) were obtained by percolation through a column of a
drying resin. Anhydrous N,N-dimethylformamide (DMF) over molecular sieves was
used as commercially supplied (Acros). Room temperature (rt) means a temperature
generally in the range of 18–20 ꢀC. Column chromatography was performed over silica
gel Kielselgel 60 (40–60 mm). Routine monitoring of reactions was carried out using
Merck silica gel 60 F254 TLC plates (TLC: thin layer chromatography) purchased from
Fluka and visualized by UV light (254 nm) inspection followed by staining with an
acidic ethanolic solution of p-anisaldehyde, or with a solution of phosphomolybdic acid

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5
Scheme 2. Synthesis of AKGs 5–7. Reagents and conditions: (i) benzyltriethylammonium chloride,
DMF, 40 ꢀC, 72 h, 81%; (j) LiBr, acetonitrile, 40 ꢀC, 72 h, 60%; (k) NaI, acetone, 40 ꢀC, 72 h, 59%; (l) p-
TsOH.H2O (0.05 equiv.), MeOH/H2O (9:1), 60 ꢀC, 5 h, 69%; (m) p-TsOH.H2O (0.05 equiv), MeOH/H2O
(9:1), 60 ꢀC, 5 h, 89%; (n) p-TsOH.H2O (0.05 equiv), MeOH/H2O (9:1), 60 ꢀC, 5 h, 74%.
(5 g in 100 mL 95% ethanol). Infrared spectra were recorded with a Thermo Nicolet
1
Avatar 250 FTIR and were reported using the frequency of absorption (cmꢂ1). H NMR
spectra (400.13 MHz) and 13C NMR spectra (100.61 MHz) were recorded on an Avance
400 Bruker spectrometer using TMS as an internal standard. Multiplicity was tabulated
using standard abbreviations: s for singlet, d for doublet, dd for doublet of doublets, t
for triplet, q for quadruplet and m for multiplet. Specific rotations were measured on a
Perkin Elmer 341 polarimeter, with 1 dm length cuvette and a continuous wave lamp at
sodium D-line (589 nm). High resolution mass spectra (HRMS) were recorded using a
MicrO-Tof-Q II spectrometer under electrospray using methanol as solvent.
Microanalyses were performed with a Flash EA1112 CHNS Thermo-Finnigan analyzer.
Compound 2,3-isopropylidene-sn-glycerol (14) (ꢃ95% pure) was purchased from Alfa
Aesar and ricinoleic acid (8) (ꢄ80% pure) was purchased from Fluka.
Synthesis
The synthetic route to prepare compounds 9–13 and 15–16 has already been described
by our research team.[10] Full experimental detail for all compounds described is pro-
vided in supplementary material.
General procedure for key intermediate 18–20
To a solution of 17 (0.3 or 0.4 mmol) in appropriate solvent (1 or 2 mL), was added
either benzyltriethylammonium chloride or LiBr or NaI (2 or 3 equiv.). The flask was
then purged with nitrogen, stoppered and dipped in a preheated bath at 40 ꢀC. Stirring
was maintained for 72 h at the same temperature. TLC monitoring showed completion
of the reaction and it was brought back to rt and solvent was evaporated. Extraction
was carried out with petroleum ether and organic layers were washed with brine and
dried over Na2SO4. Solvent was removed under reduced pressure and the crude product
was then purified by column chromatography on silica gel (0%–2% acetone in petrol-
eum ether) to provide all compounds as a colorless oil.

6
R. PEMHA ET AL.
(R)-4-((((S,Z)-12-chlorooctadec-9-en-1-yl)oxy)methyl)-2,2-dimethyl-1,3-dioxolane (18)
Compound 17 (190.7 mg, 0.4 mmol) in DMF (2 mL) was reacted with benzyltrie-
thylammonium chloride (182.2 mg, 0.8 mmol, 2 equiv.) according to the general pro-
cedure to provide 18 (135.1 mg, 81%). Rf ¼ 0.68 (petroleum ether/acetone 80:20).
IR (KBr) ꢀ 3445, 2929, 2856, 1466, 1456, 1379, 1370, 1256, 1214, 1119, 1056, 847,
725, 514 cmꢂ1
1H NMR(400 MHz, CDCl3) d 5.55–4.49 (m, 1H), 5.45–5.39 (m, 1H), 4.29–4.23 (m,
1H), 4.06 (dd, 1H, J ¼ 8.0, 8.0 Hz), 3.93–3.87 (m, 1H), 3.73 (dd, 1H, J ¼ 8.0, 8.0 Hz),
3.54–3.40 (m, 4H), 2.51–2.47 (m, 2H), 2.05–2.00 (m, 2H), 1.80–1.63 (m, 2H), 1.59–1.49
(m, 4H), 1.42–1.29 (m, 22H), 0.90–0.89 (m, 3H). 13C NMR(100 MHz, CDCl3) d 132.85
(CH¼CH), 124.91(CH¼CH), 109.37(C), 74.77 (CH), 71.88 (CH2), 71.84 (CH2), 66.94
(CH2), 63.48 (CH), 37.84 (CH2), 36.24 (CH2), 31.71 (CH2), 29.56 (CH2), 29.50 (CH2),
29.47 (CH2), 29.42 (CH2), 29.25 (CH2), 28.82 (CH2), 27.52 (CH2), 26.78 (CH3), 26.49
(CH2), 26.05 (CH2), 25.43 (CH3), 22.59 (CH2), 14.07 (CH3)
20
[a]D ¼ ꢂ16.6 (c 0.1, acetone)
Elementary analysis calculated for C24H45O3Cl: C, 69.12, H, 10.88, found: C, 69.36,
H, 10.99.
(R)-4-((((S,Z)-12-bromooctadec-9-en-1-yl)oxy)methyl)-2,2-dimethyl-1,3-dioxo-
lane (19)
Compound 17 (130 mg, 0.3 mmol) in acetonitrile (2 mL), was reacted with LiBr
(71.05 mg, 0.82 mmol, 3 equiv.) according to the general procedure to provide 19
(75 mg, 60%). Rf ¼ 0.45 (petroleum ether/acetone 95:5).
IR (KBr) ꢀ 3403, 3012, 297, 2926, 2854, 1654, 1466, 1120, 1047, 724 cmꢂ1
1H NMR(400 MHz, CDCl3) d 5.56–5.49 (m, 1H), 5.45–5.39 (m, 1H), 4.30–4.24 (m,
1H), 4.08–3.99 (m, 2H), 3.73 (dd, 1H, J ¼ 8.0, 8.0 Hz), 3.54–3.40 (m, 4H), 2.63–2.60 (m,
2H), 2.05–2.00 (m, 2H), 1.84–1.78 (m, 2H), 1.61–1.53 (m, 4H), 1.43–1.25 (m, 22H),
0.90–0.87 (m, 3H). 13C NMR(100 MHz, CDCl3) d 132.78 (CH¼CH), 125.66 (CH¼CH),
109.37 (C), 74.75 (CH), 71.87 (CH2), 71.83 (CH2), 66.93 (CH2), 57.51 (CH), 38.46
(CH2), 36.87 (CH2), 31.69 (CH2), 29.48 (CH2), 29.47 (CH2), 29.42 (CH2), 29.26 (CH2),
28.69 (CH2), 27.60 (CH2), 27.58 (CH2), 27.58 (CH2), 26.78 (CH3), 26.05 (CH2), 25.43
(CH3), 22.59 (CH2), 14.07 (CH3).
20
[a]D ¼ þ18.3 (c 0.1 CHCl3)
HRMS (ESI, m/z) calculated for C24H4579BrO3Na [M þ Na]þ: 483.249, found: 483.249
(R)-4-((((S,Z)-12-iodooctadec-9-en-1-yl)oxy)methyl)-2,2-dimethyl-1,3-dioxolane (20)
Compound 17 (100 mg, 0.3 mmol) in acetone (1 mL) was reacted with NaI (94.43 mg,
0.63 mmol, 3 equiv.) according to the general procedure to provide 20 (61.7 mg, 59%).
Rf ¼ 0.45 (petroleum ether/acetone 95:5).
IR (KBr) ꢀ 3445, 2927, 2855, 1466, 1456, 1379, 1369, 1256, 1213, 1119, 1056,
847, 724 cmꢂ1
.
1H NMR(400 MHz, CDCl3) d 5.56–5.49 (m, 1H), 5.41–5.35 (m, 1H), 4.29–4.23 (m,
1H), 4.12–4.04 (m, 2H), 3.73 (dd, 1H, J ¼ 8.0, 8.0 Hz), 3.54–3.40 (m, 4H), 2.72–2.57 (m,
2H), 2.05–1.99 (m, 2H), 1.89–1.79 (m, 1H), 1.73–1.64 (m, 1H), 1.58–1.50 (m, 4H),
1.42–1.19 (m, 22H), 0.91–0.87 (m, 3H). 13C NMR(100 MHz, CDCl3) d 132.54
(CH¼CH), 127.27 (CH¼CH), 109.36 (C), 74.76 (CH), 71.88 (CH2), 71.84 (CH2), 66.95
(CH2), 39.93 (CH2), 38.54 (CH), 38.42 (CH2), 31.68 (CH2), 29.60 (CH2), 29.56 (CH2),

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7
29.46 (2CH2), 29.42 (CH2), 29.28 (CH2), 28.48 (CH2), 27.68 (CH2), 26.79 (CH3), 26.05
(CH2), 25.44 (CH3), 22.60 (CH2), 14.07 (CH3)
20
[a]D ¼ þ5.9 (c 0.1, CHCl3)
HRMS (ESI, m/z) calculated for C24H45IO3Na [M þ Na]þ: 531.231, found: 531.231
General procedure for AKGs 5–7
To a solution either of 18 or 19 or 20 (0.1 or 0.2 or 0.4 mmol) in methanol (0.5 or 1.1
or 1.4 mL), was added p-toluenesulfonic acid monohydrate (0.05 equiv.) and distilled
water (1/10 of methanol volume). The flask was then purged with nitrogen, stoppered
and dipped in a preheated bath at 60 ꢀC. Stirring was maintained for 4 h at 60 ꢀC. TLC
monitoring showed completion of the reaction, and sodium carbonate (0.06 equiv.) was
added to the mixture and the stirring was continued for 1 h at 60 ꢀC. Methanol was
removed under reduced pressure and the crude product was purified by column chro-
matography on silica gel (0%–5% acetone in petroleum ether and then petroleum ether
þ 5% acetone þ 12% methanol) to provide AKGs 5–7 as ocher oil.
(S)-3-(((S,Z)-12-bromooctadec-9-en-1-yl)oxy)propane-1,2-diol (5)
19 (100 mg, 0.22 mmol) in methanol (1.1 mL), was added p-toluenesulfonic acid
monohydrate (2.1 mg, 0.05 equiv.) and distilled water (0.1 mL) according to the general
procedure to provide AKG 5 (81 mg, 89%). Rf ¼ 0.04 (petroleum ether/acetone 80:20).
1H NMR(400 MHz, CDCl3) d 5.56–5.49 (m, 1H), 5.45–5.37 (m, 1H), 4.05–3.99 (m,
1H), 3.88–3.84 (m, 1H), 3.72–3.64 (m, 2H), 3.56–3.50 (m, 4H), 2.83–2.80 (m, 2H),
2.19–2.17 (m, 1H), 2.08–2.00 (m, 2H), 1.84–1.78 (m, 2H), 1.61–1.53 (m, 5H), 1.38–1.26
(m, 16H), 0.90–0.89 (m, 3H). 13C NMR(100 MHz, CDCl3) d 132.75 (CH¼CH), 125.68
(CH¼CH), 72.54 (CH2), 71.83 (CH2), 70.39 (CH), 64.32 (CH2), 57.49 (CH), 38.46
(CH2), 36.87 (CH2), 31.68 (CH2), 29.57 (CH2), 29.46 (CH2), 29.44 (CH2), 29.40 (CH2),
29.25 (CH2), 28.69 (CH2), 27.57 (CH2), 27.57 (CH2), 26.07 (CH2), 22.58 (CH2),
14.06 (CH3).
20
[a]D ¼ þ11.4 (c 0.1 CHCl3)
HRMS (ESI, m/z) calculated for C21H4179BrO3Na [M þ Na]þ: 443.208, found: 443.209
(S)-3-(((S,Z)-12-iodooctadec-9-en-1-yl)oxy)propane-1,2-diol (6)
20 (50 mg, 0.01 mmol) in methanol (0.5 mL), was added p-toluenesulfonic acid mono-
hydrate (1 mg, 0.05 equiv.) and distilled water (0.05 mL) according to the general pro-
cedure to provide AKG 6 (34 mg, 74%). Rf ¼ 0.04 (petroleum ether/acetone 80:20).
1H NMR(400 MHz, CDCl3) d 5.56–5.49 (m, 1H), 5.42–5.35 (m, 1H), 4.12–4.06 (m,
1H), 3.88–3.84 (m, 1H), 3.74–3.63 (m, 2H), 3.56–3.44 (m, 4H), 2.73–2.57 (m, 3H),
2.17–2.12 (m, 1H), 2.05–2.00 (m, 2H), 1.88–1.79 (m, 1H), 1.73–1.49 (m, 7H),
1.40–1.25(m, 14H), 0.91–0.89 (m, 3H). 13C NMR(100 MHz, CDCl3) d 132.52 (CH¼CH),
127.30 (CH¼CH), 72.55 (CH2), 71.84 (CH2), 70.40 (CH), 64.33 (CH2), 39.93 (CH2),
38.56 (CH2), 38.43 (CH2), 31.68 (CH2), 29.58 (CH2), 29.60 (CH2), 29.59 (CH2), 29.45
(2CH2), 29.41 (CH2), 29.27 (CH2), 28.49 (CH2), 27.67 (CH2), 26.08 (CH2), 22.60 (CH2),
14.07 (CH3).
20
[a]D ¼ þ12.8 (c 0.1, CHCl3)
HRMS (ESI, m/z) calculated for C21H41IO3Na [M þ Na]þ: 491.199, found: 491.198
(S)-3-(((S,Z)-12-chlorooctadec-9-en-1-yl)oxy)propane-1,2-diol (7)

8
R. PEMHA ET AL.
18 (135.1 mg, 0.4 mmol) in methanol (1.4 mL), was added p-toluenesulfonic acid
monohydrate (3.32 mg, 0.05 equiv.) and distilled water (0.14 mL) according to the gen-
eral procedure to provide AKG 7 (89 mg, 69%). Rf ¼ 0.04 (petroleum ether/acet-
one 80:20).
IR (KBr) ꢀ 3393, 3013, 2928, 2855, 1654, 1466, 1120, 1047, 724 cmꢂ1
1H NMR(400 MHz, CDCl3) d 5.55–5.48 (m, 1H), 5.45–5.38 (m, 1H), 3.73–3.63 (m,
2H), 3.55–3.44 (m, 4H), 2.65 (d, 1H, J ¼ 4.0 Hz), 2.51–2.47 (m, 2H), 2.24 (broad s, 1H),
2.03 (dd, 2H, J ¼ 8.0, 12.0 Hz), 1.79–1.47 (m, 7H), 1.42–1.25 (m, 17H), 0.90–0.86 (m,
3H). 13C NMR(100 MHz, CDCl3) d 132.83 (CH¼CH), 124.93(CH¼CH), 72.53 (CH2),
71.84 (CH2), 70.43 (CH), 64.31 (CH2), 63.49 (CH), 37.84 (CH2), 36.25 (CH2), 31.71
(CH2), 29.58 (CH2), 29.49 (CH2), 29.46 (CH2), 29.41 (CH2), 29.25 (CH2), 28.82 (CH2),
27.52 (CH2), 26.49 (CH2), 26.08 (CH2), 22.59 (CH2), 14.07 (CH3).
22
[a]D ¼ ꢂ13.7 (c 0.1, CHCl3)
HRMS (ESI, m/z) calculated for C21H41O335ClNa [M þ Na]þ: 399.264, found: 399.265
Conclusion
A series of novel non-natural halogenated 1-O-alkylglycerol 5–7 analogs of a prominent
AKG of the shark liver oil (SLO) mixture were synthesized from commercially available
ricinoleic acid (8). The structures of these new compounds were characterized by NMR
experiments as well as from the HRMS data. The biological evaluation of these new
AKGs will be investigated in due course.
1
Full experimental detail and the copies of H and 13C NMR spectra for all synthetic
compounds (5–7, 9–13 and 15–20) are included in the attached supplementary materials
as the Figures: S1.1–S1.28. This material can be found via the “supplementary content”
section of this article’s webpage.
Acknowledgments
ꢀ
We thank the Agence Universitaire de la Francophonie, Region de Bretagne, CNRS (UMR 6226)
ꢀ
and the Universite de Rennes 1 for their financial support. We also thank the CRMPO (Center
ꢀ
Regional de Mesures Physiques de l’Ouest, Rennes, France) for HRMS spectra and microanalyses.
Disclosure statement
The authors declare no conflict of interest.
ORCID
ꢀ
Rene Pemha
http://orcid.org/0000-0003-3152-0685
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