A metathesis approach for the preparation of polyhydroxylated compounds as head groups in surfactant synthesis

Article abstract of DOI:10.1002/ejoc.200500614

Starting from methyl-α-D-glucopyranoside, an efficient protocol for the preparation of polyhydroxylated surfactant head-groups is demonstrated and applied in the synthesis of a typical surfactant. The key transformation is a metathesis reaction between tw

Full text of DOI:10.1002/ejoc.200500614

FULL PAPER
DOI: 10.1002/ejoc.200500614
A Metathesis Approach for the Preparation of Polyhydroxylated Compounds
as Head Groups in Surfactant Synthesis
Kristina Neimert-Andersson[a] and Peter Somfai*[a]
Keywords: Carbohydrates / Metathesis / Protecting groups / Surfactants / Polyols
Starting from methyl-α-
D
-glucopyranoside, an efficient pro-
octahydroxydecen. The importance of a strategic protecting-
group constellation for a successful metathesis reaction is
also investigated.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
tocol for the preparation of polyhydroxylated surfactant
head-groups is demonstrated and applied in the synthesis of
a typical surfactant. The key transformation is a metathesis
reaction between two monosaccharide residues to afford an
used as the hydrophobic part in commercial surfactants.[7]
It has furthermore been reported that surfactants holding
larger hydrophilic groups induce lower haemolysis com-
pared to surfactants with the same length of the hydro-
phobic chain but with a smaller hydrophilic group,[4,8–10]
the reason for why we required a strategy to easily control
the length of the hydrophilic part.
Introduction
Surfactants, also called tensides, belong to a class of
compounds that carry a hydrophilic part (often called the
head group) and a hydrophobic part (the tail group) in the
same molecule. As a result the molecules assemble at inter-
faces between hydrophilic and hydrophobic media. Adsorp-
tion of the surfactant to the interface is spontaneous and
the driving force is the lowering of interfacial energy.[1,2]
The ability of surfactants to lower the energy of a surface
in a system makes their use valuable in a wide variety of
applications, such as solubilizers and emulsifying agents in
pharmaceutical and food industry, as components in paints
and detergents, as well as in the manufacturing of papers.[1]
As the active component of a drug commonly suffers from
low water solubility, surfactants are often employed as solu-
bilizers for aqueous formulations.[3] This application re-
quires the surfactant to be nontoxic and possess a low hae-
molytic activity, as well as having a high solubilizing ca-
pacity. Existing ethylene oxide-based surfactants for drug
delivery are often complex mixtures of hundreds of dif-
ferent components. This might be beneficial for the func-
tion of the surfactant, but major drawbacks are large batch-
to-batch variations and severe side-effects, among which
histamine release might be the most acute.[4–6] Conse-
quently, there is an obvious need for new efficient surfac-
tants for drug-delivery applications that are free from ad-
verse effects. With this in mind, we wanted to design and
synthesize a surfactant with a defined composition and a
low haemolytic activity. Several reasons exist for proposing
a surfactant with the generic structure A shown in
Scheme 1. First, hydroxy fatty acids have been successfully
Scheme 1. Retrosynthetic analysis.
Following the retrosynthetic pathway outlined in
Scheme 1, surfactant A can be accessed by an ester coupling
between 12-hydroxystearic acid (B) and olefin C, which
contains a double bond that can be further derivatized.
Since carbohydrates already encompass consecutive hy-
droxy groups with a defined stereochemistry, we speculated
[a] KTH Chemical Science and Engineering, Organic Chemistry,
100 44 Stockholm, Sweden
Fax: +46-8-791-2333
E-mail: somfai@kth.se
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
978
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Polyhydroxylated Compounds as Head Groups in Surfactant Synthesis
FULL PAPER
that monosaccharides would be a suitable starting point in ceeded sluggishly and produced a mixture of by-products,
the preparation of polyol C. We needed a simple and ef- from which the 2-deoxygenated aldehyde 3a could be iso-
ficient way to extend the monosaccharide carbohydrate lated.[11] To suppress formation of this 2-dexoygenated com-
chain, and thus opted for a metathesis strategy combining pound acetylation of the hydroxy group in iodide 2 there-
the building blocks D and E to afford olefin C. Compounds fore proved necessary. After screening several solvent sys-
D and E can be obtained from a Boord-type reaction[11] of tems for the fragmentation,[18–20] addition of four equiva-
a 6-deoxy-6-halo pyranose (F). This methodology presents lents of NH4Cl to the reaction mixture[21] and LiAlH4 re-
a straightforward way to prepare polyhydroxy head-groups duction of the intermediate aldehyde 3b gave the desired
with high purity for surfactant synthesis, and can further- olefin 4a in modest yield. Several reports on cross metathe-
more be applied in the synthesis of higher sugars, which are sis with substrates containing allylic alcohols or ethers have
common structural motifs in various natural products.[12,13] been published lately, although it is unclear whether allylic
alcohols or ethers facilitate the metathesis of the adjacent
double bond or rather have an adverse effect on the reac-
Results and Discussion
tion.[22–25] As part of our synthetic plan, we therefore de-
Preparation of Head-Group Building Blocks
cided to initiate a brief investigation on alcohol protecting-
group strategies for the outcome of a metathesis reaction.
Olefin 4a therefore served as starting material for com-
pounds 4b and 4c, which have different protecting-group
constellations. To expand the number of possible metathesis
substrates olefins 4d–g were prepared from protected gluco-
side 5,[26] which was iodinated and reductively fragmented
as described for 1.
The synthesis of surfactants is complicated by the often
difficult purification of the target compounds, therefore the
choice of protecting groups is critical for the success of the
strategy − they should preferentially be removable without
need for purification in the last step. Useful alcohol protect-
ing groups are, for example, acetonide and benzyl groups.[14]
We selected two monosaccharides − glucose and galactose
− for preparation of building blocks E and F. Methyl-α--
galactopyranoside was selectively protected as the corre-
sponding 3,4-di-O-isopropylidene compound 1[15] prior
to 6-deoxyiodination, which furnished iodide 2[16,17]
Olefin Metathesis
With the seven hydroxylated olefins 4a–g in hand a sys-
(Scheme 2). The subsequent fragmentation of iodide 2 pro- tematic investigation of Ru-catalyzed metathesis conditions
Scheme 2. Preparation of terminal olefins based on -galactose and -glucose. Reaction conditions: (a) PPh3, I2, imidazole, toluene, 2:
48%, 6: 94%; (b) i) Ac2O, pyridine, DMAP, CH2Cl2, 100%; ii) Zn, NH4Cl, THF/H2O (10:1); (c) LAH, Et2O, 4a: 55% over two steps,
4d: 71% over two steps; (d) 2-methoxypropene, pTsOH, DMF, 87%; (e) i) NaH, Bu4NI, BnBr, THF, 61%. ii) HCl, THF, 85%; (f) Zn,
NH4Cl, THF/H2O (10:1); (g) DDQ, CH2Cl2/H2O (25:1), 4e: 36%, 4g: 81%; (h) TBSCl, imidazole, DMF, 69%.
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K. Neimert-Andersson, P. Somfai
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was initiated, with the intention of dimerizing olefin 4 prove this theory, substrates 4f and 4g were subjected to the
(Table 1). The two Ru catalysts 8 and 9 were chosen, of previously employed metathesis conditions, and, indeed, 4f
which 9 has been reported to be more active.[27] In this was recovered quantitatively even after stirring for several
study, however, no significant differences between the two days, while 4g was almost instantly converted into the de-
catalysts were experienced. Surprisingly, olefin 4a was com- sired dimer 7g in good yield and as a single detected isomer
pletely unreactive under the applied conditions (entries 1 (entries 9–11).
and 2), and the starting material was recovered quantita-
tively even after repeated additions of catalyst and pro-
Completion of the Surfactants
longed reaction times. Bis-acetonide 4b was equally unreac-
tive in refluxing CH2Cl2, while only decomposition prod-
ucts were isolated at 70 °C in toluene (entries 3 and 4). We
speculated that this low reactivity might result from steric
crowding in the cis-substituted five-membered acetonide
present in compounds 4a and 4b, therefore olefin 4c, which
possesses a more flexible structure, was subjected to the
same reaction conditions. The reactivity was, indeed, higher,
however only by-products were isolated (entry 5). Continu-
ing the investigation with the glucose-derived olefins 4d–g,
4d was unreactive in refluxing CH2Cl2 (entry 6), and when
the solvent was changed to toluene and the temperature
raised to 60 °C a mixture of unreacted olefin and decompo-
sition products was isolated (entry 7). The deprotected diol
4e proved to be even less suitable in the metathesis reaction
as it resulted in a mixture of unidentified products even at
room temp. (entry 8). We therefore speculated that the hy-
droxy groups at C1–C3 need to be protected, while a steri-
cally demanding protecting group on the allylic hydroxy
Delighted to have found a good dimerization protocol
for olefin 4g, we designed surfactants 10–12 with a head
group based on polyol 7g (Figure 1). It is well known that
polyhydroxy-based surfactants might suffer from low water
solubility due to favorable intermolecular hydrogen bond-
ing and high crystallization energy. Therefore surfactants 11
and 12 were designed, which are similar to surfactant 10
but presumably have a lower affinity for intermolecular hy-
drogen bonding and crystallization due to the more bulky
structure, which might aid the solubility.[28]
group cannot be tolerated in the metathesis reaction. To Figure 1. Target surfactants.
Table 1. Olefin metathesis.[a]
Entry
Olefin
Cat.
Solvent / temp. [°C]
Product / yield [%]
1
2
3
4
5
6
7
8
4a
4a
4b
4b
4c
4d
4d
4e
4f
R = R1 = C(Me)2, R2 = R3 = H, S,S
R = R1 = (CMe)2, R2 = R3 = H, S,S
R = R1 = R2 = R3 = C(Me)2, S,S
9
CH2Cl2 / 40
toluene / 70
CH2Cl2 / 40
toluene / 70
toluene / 70
CH2Cl2 / r.t.
toluene / 60
CH2Cl2 / r.t.
CH2Cl2 / r.t.
toluene / 60
CH2Cl2 / 40
– / 0[b]
– / 0[b]
– / 0[b]
– / 0[c]
– / 0[c]
– / 0[b]
– / 0[d]
– / 0[c]
– / 0[b]
– / 0[d]
7g / 67[e]
8/9
8/9
8/9
8
R = R1 = R2 = R3 = (CMe)2, S,S
R = R1 = H, R2 = R3 = Bn, S,S
R = PMB, R1 = R2 = Bn, R3 = H; R,R
R = PMB, R1 = R2 = Bn, R3 = H; R,R
R = R3 = H, R1 = R2 = Bn; R,R
8
8
8
9
10
11
R = PMB, R1 = R2 = Bn, R3 = TBS; R,R
R = PMB, R1 = R2 = Bn, R3 = TBS; R,R
R = H, R1 = R2 = Bn, R3 = TBS; R,R
8
4f
8
4g
8
[a] Reaction conditions: (a) Catalysts 8 or 9[27] (10–20 mol-%) in CH2Cl2 at room temp. to 40 °C or in toluene at 60–70 °C. No significant
differences were seen between the two catalysts. [b] Starting material was recovered. [c] Starting material was consumed. [d] Starting
material was recovered together with decomposition products. [e] E:Z Ͼ 99:1, Determined from coupling constants in compound 19.
980
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Polyhydroxylated Compounds as Head Groups in Surfactant Synthesis
FULL PAPER
Starting from olefin 7g, the allylic hydroxy groups were
successfully benzylated,[29] acylated, and methylated to give
13, 14, and 15 respectively (Scheme 3). Cleavage of the TBS
groups to deliver alcohols 16, 17, and 18, respectively, was
accomplished under acidic conditions,[30] which proved nec-
essary in order to circumvent scrambling of the acetyl
groups in 17. To selectively obtain the monoester rather
than the bis-ester in the subsequent esterification step, a
fivefold excess of alcohols 16–18 to the (R)-12-hydroxystea-
ric acid[31] was used. This stoichiometry, in combination
with the Yamaguchi esterification protocol,[32] successfully
provided the desired surfactant precursors 19–21, together
with recovered alcohols 16–18. From the coupling con-
stants of the vinylic protons in ester 19 it was furthermore
possible to verify the stereochemistry of the double bond
to be E (J = 15.5 Hz).
Scheme 4. Hydrogenolysis of compound 19. Reaction conditions:
(a) H2, Pd/C, MeOH, 61%.
Conclusions
Using a Ru-catalyzed metathesis reaction as the key step
we have developed an efficient synthesis of polyhy-
droxylated compounds to be used as surfactant head-
groups. This strategy allows the synthesis of enantiomer-
ically pure surfactants and should permit the synthesis of
polyols with a different stereochemistry from other mono-
saccharides as starting materials. We have also demon-
strated the importance of using a tactical protecting-group
constellation to be successful in olefin metathesis of hydrox-
ylated compounds. The surface chemical properties of sur-
factant 10 will be evaluated and presented in due course.
Experimental Section
1
General: H and 13C NMR spectra were recorded on Bruker dpx
400 MHz or avance 500 MHz spectrometers in CDCl3 or CD3OD
using the residual peak of the corresponding solvent (1H NMR: δ =
7.26 and 3.33 ppm, respectively; 13C NMR: δ = 77.0 and 49.0 ppm,
respectively) or added TMS (δ = 0.00 ppm), as internal standard.
Optical rotations, [α]D were measured on a Perkin–Elmer 343 po-
larimeter at the sodium D line at ambient temperature. Infrared
spectra were recorded with an ATI Mattson FTIR spectrophotom-
eter, and only the strongest/structurally most important peaks are
listed. High-resolution mass spectra were recorded with a JEOL
SX-102 spectrometer. Analytical thin-layer chromatography was
performed on Merck silica gel 60 F254 plates, and visualized with
UV light and phosphomolybdic acid staining reagent (5 wt.-% solu-
tion in EtOH) or H2SO4 (5 wt.-% solution in EtOH). Flash
chromatography employed Grace Amicon silica gel 60 (35–70 µm)
or Biotage SP4 flash system using Flash 12+M, 25+M and 40+M
cartridges. Air- and moisture-sensitive reactions were carried out
in flame-dried, septum-capped flasks under an atmospheric pres-
sure of nitrogen. All liquid reagents were transferred with oven-
dried syringes. THF and CH2Cl2 were taken from a GlassContour
Seca Solvent system or freshly distilled from sodium-benzophenone
ketyl and CaH2, respectively. DMF and toluene were taken from a
GlassContour Seca Solvent system.
Scheme 3. Preparation of surfactant precursors 19–21. Reaction
conditions: (a) KHMDS, BnBr, THF, –78 °C Ǟ room temp., 71%;
(b) Ac2O, Et3N, DMAP, CH2Cl2, 99%; (c) KHMDS, MeI, THF,
–78 °C Ǟ room temp., 99%; (d) HOAc/H2O/THF (1:3:3), 50 °C,
16: 79%, 17: 73%, 18: 99%; (e) (R)-12-hydroxystearic acid, 2,4,6-
trichlorobenzoyl chloride, Et3N, DMAP, 19: 73%, 20: 84%, 21:
82%.
(S)-1-[(4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]ethane-1,2-
diol (4a). Acetylation of compound 2: Ac2O (28 mL, 29.1 mmol),
pyridine (1.17 mL, 14.55 mmol), and DMAP (cat.) were added to
a solution of compound 2[16,17] (1.9 g, 5.5 mmol) in CH2Cl2
(150 mL). The reaction mixture was stirred overnight and then
washed with H2O, dried (MgSO4), and evaporated to give the ace-
tate in 94% yield (2.0 g, 5.17 mmol). This material was immediately
used for the Zn-promoted ring opening reaction.
Benzyl ethers are frequently used as hydroxy protecting
groups since the hydrogenolytic deprotection usually only
requires filtration and evaporation as workup.[14,33] This
methodology was successfully applied to yield surfactant 10
(Scheme 4). A bit surprisingly, surfactant precursors 20 and
21 gave inseparable product mixtures when treated with H2
and Pd/C in a variety of solvents and under different pres-
sures, which forced us to temporarily leave those com-
pounds.[34]
General Procedure for the Reductive Opening of 6-Deoxy-6-iodo-
hexoses. Synthesis of Compounds 4a–4d: The protected sugar (2.0 g,
5.17 mmol) was redissolved in THF/H2O (11:1, 220 mL). Zn dust
(3.4 g, 52.3 mmol) and NH4Cl (1.1 g, 20.9 mmol) were added and
the reaction mixture heated at 50 °C until no starting material re-
mained (Ͻ10 min, TLC). The reaction mixture was cooled to room
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K. Neimert-Andersson, P. Somfai
FULL PAPER
temp., and was then filtered through a plug of celite and concen-
trated to give the crude aldehyde. The oily residue was redissolved
in Et2O (80 mL) and then transferred through a cannula into a
suspension of LiAlH4 (595 mg, 15.7 mmol) in Et2O (80 mL) at
0 °C. The cooling bath was removed and the reaction mixture al-
lowed to reach room temp. over 30 min. The product was isolated
by careful addition of Na2SO4·10H2O until gas evolution ceased,
followed by successive addition of H2O (595 µL), NaOH (15 %,
595 µL), and H2O (1785 µL). After stirring for 1 h the formed white
crystals were filtered off, and the eluent concentrated to give the
crude product. Flash chromatography (EtOAc/MeOH, 6:1) gave
the title compound 4a as a clear oil in 55 % yield (544 mg,
2.89 mmol). 1H NMR (400 MHz, CDCl3): δ = 5.99 (ddd, J = 17.2,
10.2, 8.2 Hz, 1 H), 5.71 (d, J = 17.2 Hz, 1 H), 5.31 (d, J = 10.2 Hz,
1 H), 4.61 (t, J = 7.7 Hz, 1 H), 4.19 (dd, J = 6.8, 5.1 Hz, 1 H),
3.70–3.53 (m, 3 H), 3.14 (br. s, 2 H), 1.53 (s, 3 H), 1.39 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 134.1, 120.3, 109.3, 79.4,
Methyl-2,3-di-O-benzyl-6-iodo-4-O-(4-methoxybenzyl)-6-deoxy-α-
D
-glucopyranoside (6): This compound was prepared from 5[26] as
described previously[16,17] and obtained as a white powder in 94%
yield. H NMR (400 MHz, CDCl3): δ = 7.38–7.29 (m, 10 H), 7.20
1
(d, J = 8.7 Hz, 2 H), 6.86 (d, J = 8.7 Hz, 2 H), 4.99 (d, J = 10.9 Hz,
1 H), 4.87–4.78 (m, 3 H), 4.68–4.60 (m, 3 H), 4.00 (t, J = 9.2 Hz,
1 H), 3.80 (s, 3 H), 3.53 (dd, J = 9.6, 3.6 Hz, 1 H), 3.47–3.42 (m,
2 H), 3.41 (s, 3 H), 3.34–3.24 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.4, 138.5, 137.9, 130.1, 129.6, 128.5, 128.4, 128.1,
128.0, 127.9, 127.7, 113.9, 98.1, 81.6, 81.1, 80.0, 75.7, 75.0, 73.4,
69.3, 55.5, 55.3, 7.7 ppm. IR (neat): ν = 2908, 1514, 1250,
˜
1068 cm–1. [α]D = +49.3 (c = 1.00, CH2Cl2). HRMS (FAB+): calcd.
for C29H33O6NaI [M + Na] 627.1220; found 627.1224.
(2S,3S,4R)-2,3-Bis(benzyloxy)-4-(4-methoxybenzyloxy)hex-5-en-1-
ol (4d): This compound was prepared from 6 as described for 4a
and used without further purification. 1H NMR (400 MHz,
CDCl3): δ = 7.32–7.26 (m, 10 H), 7.22 (d, J = 8.6 Hz, 2 H), 6.85
(d, J = 8.6 Hz, 2 H), 5.91–5.83 (m, 1 H), 5.31 (d, J = 6.0 Hz, 1 H),
5.27 (s, 1 H), 4.71 (s, 2 H), 4.60 (s, 2 H), 4.56 (d, J = 11.4 Hz, 1
H), 4.29 (d, J = 11.4 Hz, 1 H), 4.06 (dd, J = 7.3, 4.3 Hz, 1 H), 3.79
(s, 3 H), 3.72–3.61 (m, 3 H), 3.55–3.50 (m, 1 H), 2.19 (t, J = 6.3 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 259.7, 138.9, 138.7,
135.7, 130.4, 130.1, 128.9, 128.83, 128.78, 128.3, 128.2, 128.1,
119.2, 114.2, 82.2, 80.4, 80.0, 75.2, 73.2, 70.8, 61.8, 55.7 ppm. IR
78.2, 70.2, 64.6, 27.7, 25.4 ppm. IR (neat): ν = 3369 cm–1 (br), 2985,
˜
1072, 883 cm–1. [α]D = +36.9 (c = 1.00, CH2Cl2). HRMS (FAB+):
calcd. for C9H17O4 [M + H] 189.1127; found 189.1128.
(S)-4-[(4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]-2,2-dimethyl-
1,3-dioxolane (4b): 2-Methoxypropene (44 µL, 0.465 mmol) was
added to a solution of 4a (21 mg, 0.116 mmol) and pTsOH (cat.)
in DMF (1 mL). The reaction mixture was stirred at room temp.
for 10 min, and then diluted with Et2O (1.5 mL) and H2O (0.5 mL)
and filtered through an Extrelut® NT3 tube. The organic layer was
eluted with CH2Cl2 (15 mL) and concentrated to give the title com-
(neat): ν = 3469 cm–1 (br), 2872, 1066, 698 cm–1. [α]D = –7.2 (c =
˜
0.29, CH2Cl2). HRMS (FAB+): calcd. for C28H33O5 [M + H]
449.2329; found 449.2328.
1
pound 4b as a colorless oil in 87% yield (23 mg, 0.101 mmol). H
General Procedure for the PMB Deprotection Using DDQ. Synthesis
of (2S,3S,4R)-2,3-Bis(benzyloxy)hex-5-ene-1,4-diol (4e): H2O
(0.4 mL) and DDQ (183 mg, 0.804 mmol) were added to a solution
of compound 4d (328 mg, 0.731 mmol) in CH2Cl2 (10 mL). The
reaction mixture was stirred vigorously for 1 h, and then quenched
by the addition of NaHCO3. The phases were separated and the
organic layer was washed with brine, dried (MgSO4), and the sol-
vents evaporated. Flash chromatography (EtOAc/pentane 5% Ǟ
50 %) gave 4e in 84 % yield (202 mg, 0.615 mmol). 1H NMR
(400 MHz, CDCl3): δ = 7.37–7.26 (m, 10 H), 5.91 (ddd, J = 17.1,
10.3, 5.0 Hz, 1 H), 5.34 (td, J = 17.1, 1.4 Hz, 1 H), 5.19 (td, J =
10.3, 1.4 Hz, 1 H), 4.66 (d, J = 11.3 Hz, 1 H), 4.65 (d, J = 11.7 Hz,
1 H), 4.60 (d, J = 11.3 Hz, 1 H), 4.59 (d, J = 11.7 Hz, 1 H), 4.40–
4.35 (m, 1 H), 3.84–3.76 (m, 2 H). 3.68–3.61 (m, 1 H), 3.58 (dd, J
= 5.8, 2.8 Hz, 1 H), 2.68 (d, J = 7.3 Hz, 1 H), 2.48 (dd, J = 6.5,
6.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.5, 138.1,
137.8, 128.5, 128.4, 128.2, 128.0, 127.9, 115.7, 80.8, 79.0, 74.5, 72.5,
71.1, 60.6 ppm; two carbon signals are overlapping at δ =
NMR (400 MHz, CDCl3): δ = 5.77 (ddd, J = 17.1, 10.2, 8.4 Hz, 1
H), 5.27 (d, J = 17.1 Hz, 1 H), 5.22 (d, J = 10.2 Hz, 1 H), 4.47 (dd,
J = 8.4, 6.3 Hz, 1 H), 4.11–4.02 (m, 2 H), 3.93 (dd, J = 8.3, 6.3 Hz,
1 H), 3.51 (dd, J = 8.2, 7.0 Hz, 1 H), 1.48 (s, 3 H), 1.39 (s, 3 H),
1.34 (s, 3 H), 1.30 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 134.0, 119.6, 109.69, 109.66, 80.1, 78.6, 75.1, 65.8, 27.7, 26.6,
25.29, 25.25 ppm. IR (neat): ν = 2983, 1371, 1066, 868 cm–1. [α]
˜
D
= +6.3 (c = 0.95, CH2Cl2); m.p. 62.3–63.3 °C. HRMS (FAB+):
calcd. for C12H20O4 [M+] 228.1362; found 228.1338.
(3S,4S,5S)-5,6-Bis(benzyloxy)hex-1-ene-3,4-diol (4c): NaH (5 mg,
0.124 mmol, 60 wt.-% dispersion in oil) was washed twice with pen-
tane and then suspended in DMF (2 mL) and cooled to 0 °C. Com-
pound 4a (11 mg, 0.0606 mmol), BnBr (22 µL, 0.182 mmol), and
Bu4NI (2.2 mg, 0.00606 mmol) were added and the reaction mix-
ture was allowed to reach room temp. overnight. The reaction was
quenched by the addition of H2O (5 mL) and the mixture was ex-
tracted with Et2O (10 mL). The organic layer was dried (MgSO4)
and concentrated. Flash chromatography (pentane/EtOAc, 15:1)
gave the corresponding bis-benzyl ether as a colorless oil in 61%
yield (13.7 mg, 0.0371 mmol). This material was then stirred with
HCl (1 , 1.5 mL) in THF (1.5 mL) at 40 °C for 1 h. The THF
was evaporated, Et2O (1 mL) was added, and the biphasic mixture
filtered through an Extrelut® NT3 tube. The organic phase was
eluted with CH2Cl2 (15 mL). Concentration afforded the title com-
127.9 ppm. IR (neat): ν = 3415, 1095, 739, 698 cm–1. [α] = +25.3
˜
D
(c = 1.02, CH2Cl2). HRMS (FAB+): calcd. for C20H25O4 [M + H]
329.1754; found 329.1750.
tert-Butyl-[(2S,3S,4R)-2,3-bis(benzyloxy)-4-(4-methoxybenzyloxy)-
hex-5-enyloxy]dimethylsilane (4f): Compound 4d (5.1 g, 11.4 mmol)
was stirred with TBDMSCl (1.9 g, 12.5 mmol) and imidazole
(1.55 g, 22.8 mmol) in DMF (250 mL) at room temp. overnight.
1
pound 4c as a colorless oil in 85% yield (10 mg, 0.0316 mmol). H
NMR (400 MHz, CDCl3): δ = 7.32–7.17 (m, 10 H), 5.86 (ddd, J = The reaction mixture was diluted with Et2O (300 mL) and washed
17.2, 10.6, 5.5 Hz, 1 H), 5.26 (td, J = 17.2, 1.6 Hz, 1 H), 5.16 (td,
J = 10.6, 1.5 Hz, 1 H), 4.70 (d, J = 11.3 Hz, 1 H), 4.52–4.45 (m, 3
H), 4.17–4.12 (m, 1 H), 3.81 (dt, J = 5.1, 3.0 Hz, 1 H), 3.71–3.60
with H2O and brine. The organic phase was dried (MgSO4) and
concentrated. After purification with flash chromatography
(EtOAc/pentane 5% Ǟ 50%) 4f was obtained in 69% yield (4.42 g,
(m, 3 H), 2.68 (d, J = 7.3 Hz, 1 H), 2.53 (d, J = 7.2 Hz, 1 H) ppm. 7.85 mmol). 1H NMR (400 MHz, CDCl3): δ = 7.32–7.16 (m, 12
13C NMR (125 MHz, CDCl3): δ = 137.84, 137.78, 137.5, 128.6,
H), 6.80 (d, J = 8.8 Hz, 2 H) 5.76 (ddd, J = 17.1, 10.6, 7.8 Hz, 1
H) 5.23–5.15 (m, 2 H), 4.76 (d, J = 11.7 Hz, 1 H), 4.64 (d, J =
11.7 Hz, 2 H), 4.51 (d, J = 11.7 Hz, 2 H), 4.29 (d, J = 11.7 Hz, 1
H), 4.08 (dd, J = 7.6, 6.0 Hz, 1 H), 3.74 (s, 3 H), 3.66–3.54 (m, 4
H), 0.83 (s, 9 H), –0.055 (s, 3 H), –0.060 (s, 3 H) ppm. 13C NMR
128.5, 128.2, 128.1, 127.8, 127.7, 116.3, 77.4, 74.2, 73.6, 73.5, 72.8,
70.4 ppm. IR (neat): ν = 3442 cm–1 (br), 2868, 1097, 737 cm–1
.
˜
[α]D = +5.0 (c = 0.38, CH2Cl2). HRMS (FAB+): calcd. for
C20H25O4 [M + H] 329.1754; found 329.1757.
982
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 978–985

Polyhydroxylated Compounds as Head Groups in Surfactant Synthesis
FULL PAPER
(100 MHz, CDCl3): δ = 159.5, 139.44, 139.36, 136.3, 131.0, 130.1, (E,2R,3S,4R,7R,8S,9R)-4,7-Bis(acetoxy)-2,3,8,9-tetra(benzyloxy)-
128.8, 128.63, 128.56, 128.3, 127.9, 127.8, 119.0, 114.1, 81.61, 1,10-bis(tert-butyldimethylsilyloxy)dec-5-ene (14): Alcohol 7g
81.58, 80.6, 75.6, 73.5, 70.8, 63.1, 55.7, 26.3, 18.6, –4.97, –5.0 ppm.
(43 mg, 0.498 mmol) was stirred together with Ac2O (47 µL,
IR (neat): ν = 1250, 1088, 837 cm–1. [α]D = –12.4 (c = 0.59, 0.498 mmol), Et3N (35 µL, 0.249 mmol), and DMAP (cat.) in
˜
CH2Cl2). HRMS (FAB+): calcd. for C34H47O5Si [M + H] 563.3194;
found 563.3193.
CH2Cl2 (2 mL) for 14 h at room temp. The reaction mixture was
then diluted with H2O and filtered through an Extrelut® NT3 tube
and eluted with CH2Cl2 (15 mL). Evaporation of the solvent gave
14 in 90% yield (42 mg, 0.0448 mmol). The compound was used
without further purification. 1H NMR (500 MHz, CDCl3): δ =
7.29–7.20 (m, 20 H), 5.68 (dd, J = 3.8, 1.9 Hz, 2 H), 5.55–5.49 (m,
2 H), 4.64–4.56 (m, 6 H), 4.51 (d, J = 12.0 Hz, 2 H), 3.70 (dd, J =
10.6, 5.7 Hz, 2 H), 3.64 (dd, J = 6.0, 4.4 Hz, 2 H), 3.56 (dd, J =
10.6, 5.4 Hz, 2 H), 3.49 (app. dd, J = 9.8, 5.4 Hz, 2 H), 1.87 (s, 6
H), 0.84 (s, 18 H), –0.02 (s, 6 H), –0.03 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 169.7, 138.7, 138.5, 129.5, 128.3, 128.2,
127.8, 127.50, 127.48, 80.1, 79.9, 74.9, 73.9, 73.1, 62.0, 25.9, 21.1,
18.2, –5.40, –5.43 ppm; two carbon signals are overlapping at δ =
(2R,3S,4R)-2,3-Bis(benzyloxy)-1-(tert-butyldimethylsilyloxy)hex-5-
en-4-ol (4g): This compound was prepared as described for 4e and
obtained in 81 % yield (2.8 g, 6.35 mmol). 1H NMR (400 MHz,
CDCl3): δ = 7.38–7.29 (m, 10 H), 5.94 (ddd, J = 17.2, 10.5, 5.6 Hz,
1 H), 5.35 (td, J = 17.2, 1.6 Hz, 1 H), 5.20 (td, J = 10.5, 1.6 Hz, 1
H), 4.75 (d, J = 11.3 Hz, 1 H), 4.73 (d, J = 11.8 Hz, 1 H), 4.66 (d,
J = 11.3 Hz, 1 H), 4.62 (d, J = 11.8 Hz, 1 H), 4.40–4.36 (m, 1 H),
3.87 (AB-dd, J = 11.0, 5.1 Hz, 1 H), 3.85 (AB-dd, J = 11.0, 4.7 Hz,
1 H), 3.68 (q, J = 5.0 Hz, 1 H), 3.62 (dd, J = 5.1, 3.9 Hz, 1 H),
2.95 (d, J = 5.8 Hz, 1 H), 0.94 (s, 9 H), 0.10 (s, 3 H), 0.098 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 138.5, 138.4, 138.34,
128.32, 128.1, 127.9, 127.8, 127.6, 115.8, 81.6, 80.3, 74.8, 73.0, 71.9,
127.8 ppm. IR (neat): ν = 2929, 1743, 1232, 1093, 837 cm–1. [α]
˜
D
62.4, 25.9, 18.0, –5.39, –5.45 ppm. IR (neat): ν = 3450 cm–1 (br),
= –4.75 (c = 0.80, CH2 Cl2 ). HRMS (FAB+): calcd. for
C54H76NaO10Si2 [M + Na] 963.4875; found 963.4877.
˜
1256, 1093, 837 cm–1. [α]D = +18.0 (c = 1.00, CH2Cl2). HRMS
(FAB+): calcd. for C26H39O4Si [M + H] 443.2618; found 443.2623.
(E,2R,3S,4R,7R,8S,9R)-2,3,8,9-Tetra(benzyloxy)-1,10-bis(tert-
butyldimethylsilyloxy)-4,7-bis(methoxy)-dec-5-ene (15): This com-
pound was prepared from 7g and MeI as described for 13, and
obtained in 99% yield. 1H NMR (500 MHz, CDCl3): δ = 7.30–7.21
(m, 20 H), 5.64 (dd, J = 4.4, 2.2 Hz, 2 H), 4.70–4.61 (m, 6 H), 4.55
(d, J = 12.0 Hz, 2 H), 3.84 (ddd, J = 6.9, 4.7, 2.2 Hz, 2 H), 3.78
(dd, J = 10.7, 4.4 Hz, 2 H), 3.71 (dd, J = 10.7, 6.0 Hz, 2 H), 3.65
(app. dd, J = 10.1, 4.4 Hz, 2 H), 3.49 (t, J = 4.7 Hz, 2 H), 3.23 (s,
6 H), 0.87 (s, 18 H), 0.02 (s, 12 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 138.9, 138.7, 131.4, 128.22, 128.19, 128.17, 127.9,
127.5, 82.2, 81.5, 80.4, 74.9, 73.1, 63.1, 56.7, 25.9, 18.2, –5.37,
–5.39 ppm; the two missing carbon signals are overlapping with the
(E,2R,3S,4R,7R,8S,9R)-2,3,8,9-tetra(Benzyloxy)-1,10-bis(tert-
butyldimethylsilyloxy)dec-5-ene-4,7-diol (7g): Compound 4g (5 mg,
0.0113 mmol) was dissolved in CH2Cl2 (0.5 mL) and Grubbs’ sec-
ond-generation catalyst (1 mg, 1.13 µmol) was added to this solu-
tion. The solution was heated to 40 °C and after 3 h the starting
material had been consumed, as judged by TLC. Evaporation of
the solvent and purification by flash chromatography (pentane/
EtOAc, 4:1) provided olefin 7g in 66% yield (3.2 mg, 3.73 µmol).
1H NMR (400 MHz, CDCl3): δ = 7.33–7.17 (m, 20 H), 5.74 (dd, J
= 2.8, 1.0 Hz, 2 H), 4.64 (d, J = 11.6 Hz, 4 H), 4.59–4.51 (m, 4 H),
4.31–4.26 (m, 2 H), 3.79 (dd, J = 11.1, 5.3 Hz, 2 H), 3.75 (dd, J =
11.1, 4.5 Hz, 2 H), 3.60 (app. q J = 5.0 Hz, 2 H), 3.49 (dd, J = 5.5,
3.8 Hz, 2 H), 2.72 (d, J = 6.0 Hz, 2 H), 0.86 (s, 18 H), 0.02 (s, 6
H), 0.01 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.5,
138.2, 131.7, 128.31, 128.28, 128.2, 127.9, 127.7, 127.6, 81.5, 80.4,
signals at δ = 127–129 ppm. IR (neat): ν = 2929, 2856, 1454, 1254,
˜
1090, 837 cm–1. [α]D = –10.0 (c = 0.91, CH2Cl2). HRMS (FAB+):
calcd. for C52H76NaO8Si2 [M + Na] 907.4977; found 907.4971.
General Procedure for the TBS-Deprotection of Compounds 13–15.
Synthesis of Alcohols 16–18. (E,2S,3S,4R,7R,8S,9S)-2,3,4,7,8,9-
Hexa(benzyloxy)dec-5-ene-1,10-diol (16): Silyl ether 13 (359 mg,
0.346 mmol) was dissolved in THF (15 mL). H2O (15 mL) and
HOAc (5 mL) were added and the reaction mixture heated to 50 °C
for 24 h. After cooling to room temp., the reaction mixture was
transferred to a separation funnel containing Et2O, and NaHCO3
(aq) was added. The phases were separated and the aqueous layer
was extracted twice with Et2O. The combined organic phases were
dried (MgSO4) and evaporated to give 292 mg of a crude oil. Purifi-
cation with flash chromatography (EtOAc/pentane 5% Ǟ 100%)
74.6, 73.0, 71.1, 62.7, 25.9, 18.2, –5.39, –5.42 ppm. IR (neat): ν =
˜
3442 cm–1 (br), 1255, 1095, 837 cm–1. [α]D = +11.3 (c = 0.96,
CH2Cl2). HRMS (FAB+): calcd. for C50H72O8Si2Na [M + Na]
879.4664; found 879.4664.
General Procedure for the O-Alkylation of Alcohol 7g. Synthesis of
13–15. (E,2R,3S,4R,7R,8S,9R)-2,3,4,7,8,9-Hexa(benzyloxy)-1,10-
bis(tert-butyldimethylsilyloxy)dec-5-ene (13): KHMDS
(0.187 mmol, 0.4 mL of a 0.5  solution in toluene) was added
dropwise to a solution of 7g (40 mg, 0.0467 mmol) and alkyl halide
(BnBr, 56 µL, 0.467 mmol) in THF (5 mL) at –78 °C. The reaction
mixture was allowed to reach room temp. overnight, and the reac-
tion was then quenched by the addition of Na2CO3 (sat.). The
phases were separated and the aqueous phase was extracted three
times with Et2O. Drying (MgSO4) and evaporation gave 108 mg of
a crude oil that was purified with flash chromatography (EtOAc/
pentane 5% Ǟ 10%) to give 13 as a clear oil in 86% yield (41.8 mg,
1
gave 16 in 79% yield (222 mg, 0.274 mmol). H NMR (400 MHz,
CDCl3): δ = 7.41–7.27 (m, 30 H), 5.85 (dd, J = 4.3, 2.0 Hz, 2 H),
4.75 (d, J = 11.5 Hz, 2 H), 4.72 (d, J = 11.5 Hz, 2 H), 4.63 (d, J =
11.7 Hz, 2 H), 4.61 (s, 4 H), 4.43 (d, J = 11.7 Hz, 2 H), 4.18–4.14
(m, 2 H), 3.76–3.70 (m, 2 H), 3.67–3.57 (m, 6 H), 2.23 (dd, J = 7.3,
5.8 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.3, 138.2,
137.7, 131.2, 128.4, 128.39, 128.36, 128.3, 127.9, 127.83, 127.79,
127.7, 81.6, 79.6, 79.5, 74.7, 72.7, 71.0, 61.4 ppm; the two missing
carbon signals are overlapping with the signals at δ = 127–129 ppm.
1
0.0403 mmol). H NMR (400 MHz, CDCl3): δ = 7.33–7.24 (m, 30
H), 5.76 (dd, J = 4.3, 2.1 Hz, 2 H), 4.79 (d, J = 11.6 Hz, 2 H), 4.70
(d, J = 11.6 Hz, 2 H), 4.68 (d, J = 11.7 Hz, 2 H), 4.62 (d, J =
11.8 Hz, 2 H), 4.55 (d, J = 11.7 Hz, 2 H), 4.41 (d, J = 11.8 Hz, 2
H), 4.19–4.16 (m, 2 H) 3.76–3.62 (m, 8 H), 0.88 (s, 18 H), 0.01 (s,
6 H), 0.00 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.8,
138.7, 138.3, 131.7, 128.3, 128.2, 128.1, 127.9, 127.8, 127.5, 127.4,
IR (neat): ν = 3431 cm–1 (br), 2868, 1454, 1027, 1072, 735,
˜
698 cm–1. [α]D = –0.42 (c = 0.48, CH2Cl2). HRMS (FAB+): calcd.
for C52H56NaO8 [M + Na] 831.3873; found 831.3867.
81.3, 80.3, 80.1, 75.0, 73.0, 70.9, 63.0, 25.9, 18.2, –5.4 ppm. IR (E,2S,3S,4R,7R,8S,9S)-4,7-Bis(acetoxy)-2,3,8,9-tetra(benzyloxy)-
(neat): ν = 2927, 1092, 837 cm–1. [α] = –9.1 (c = 0.7, CH2Cl2). dec-5-ene-1,10-diol (17): This compound was prepared as described
˜
D
1
HRMS (FAB+): calcd. for C64H84NaO8Si2 [M + Na] 1059.5603;
found 1059.5592.
for 16 and obtained in 73% yield. H NMR (500 MHz, CDCl3): δ
= 7.30–7.16 (m, 20 H), 5.70 (dd, J = 3.3, 1.4 Hz, 2 H), 5.43 (app.
Eur. J. Org. Chem. 2006, 978–985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
983

K. Neimert-Andersson, P. Somfai
FULL PAPER
t, J = 3.9 Hz, 2 H), 4.60 (s, 4 H), 4.56 (d, J = 11.7 Hz, 2 H), 4.50
(d, J = 11.7 Hz, 2 H), 3.69–3.62 (m, 2 H), 3.60 (t, J = 5.4 Hz, 2
(E,2S,3S,4R,7R,8S,9S,12ЈR)-4,7-Bisacetoxy-2,3,8,9-tetra(benzyl-
oxy)-10-hydroxy-dec-5-enyl 12-Hydroxystearate (20): This com-
H), 3.52–3.44 (m, 4 H), 1.91 (s, 6 H), 1.83 (t, J = 6.3 Hz, 2 H) ppm. pound was prepared from 17 as described for 19 and obtained in
13C NMR (125 MHz, CDCl3): δ = 169.8, 138.2, 137.9, 128.8, 128.5, 84% yield together with 77% of unreacted alcohol 17. 1H NMR
128.4, 128.0, 127.87, 127.86, 127.83, 80.2, 79.5 74.6, 73.2, 73.1,
61.4, 21.1 ppm. IR (neat): ν = 2875, 1739, 1232, 1078 cm–1. [α]
+3.1 (c = 0.65, CH2Cl2). HRMS (FAB+): calcd. for C42H48NaO10
(400 MHz, CDCl3): δ = 7.36–7.24 (m, 20 H), 5.79–5.69 (m, 2 H),
5.49 (dd, J = 10.6, 5.0 Hz, 2 H), 4.67–4.60 (m, 6 H), 4.59–4.51 (m,
2 H), 4.33 (dd, J = 11.7, 4.0 Hz, 1 H), 4.09 (dd, J = 11.7, 6.0 Hz,
1 H), 3.75–3.69 (m, 2 H), 3.69–3.64 (m, 1 H), 3.62–3.53 (m, 4 H),
2.25 (t, J = 7.6 Hz, 2 H), 2.15–1.99 (m, 2 H), 1.98 (s, 3 H), 1.96 (s,
3 H), 1.65–1.52 (m, 2 H), 1.43 (s, 6 H), 1.35–1.20 (m, 20 H), 0.88
(t, J = 6.5 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 173.5,
169.8, 138.2, 138.1, 137.94, 137.88, 129.3, 128.7, 128.5, 128.41,
128.37, 128.0, 127.90, 127.88, 127.83, 127.80, 127.7, 80.1, 79.7,
79.4, 74.60, 74.56, 73.2, 73.1, 73.09, 73.06, 72.0, 63.4, 61.3, 37.5,
34.2, 31.8, 29.7, 29.6, 29.5, 29.43, 29.37, 29.3, 29.1, 25.6, 24.9, 22.6,
21.08, 21.05, 14.1 ppm; the two acetyl carbonyl carbon signals are
overlapping at δ = 169.8 ppm, three missing aromatic carbon sig-
nals are overlapping with signals at δ = 127.5–128.5 ppm, one ben-
zylic carbon signal is not visible, and two signals from the tail
group are overlapping with signals at δ = 25.5–30.5 ppm. IR (neat):
=
˜
D
[M + Na] 735.3145; found 735.3149.
(E,2S,3S,4R,7R,8S,9S)-2,3,8,9-Tetra(benzyloxy)-4,7-bis(methoxy)-
dec-5-ene-1,10-diol (18): This compound was prepared as described
1
for 16 and obtained in 99% yield. H NMR (500 MHz, CDCl3): δ
= 7.27–7.19 (m, 20 H), 5.66 (dd, J = 4.3, 2.0 Hz, 2 H), 4.62 (d, J
= 11.3 Hz, 2 H), 4.54 (d, J = 11.3 Hz, 2 H), 4.51 (s, 4 H), 3.79–
3.76 (m, 2 H), 3.71–3.66 (m, 2 H), 3.59–3.49 (m, 4 H), 3.47 (dd, J
= 5.7, 4.1 Hz, 2 H), 3.19 (s, 6 H), 2.24 (s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 138.3, 138.1, 131.3, 128.43, 128.37, 128.3,
127.9, 127.82, 127.76, 81.7, 81.6, 79.7, 74.7, 72.7, 61.4, 56.8 ppm.
IR (neat): ν = 3444, 2929, 1454, 1074 cm–1. [α] = –3.4 (c = 0.58,
˜
D
CH2Cl2). HRMS (FAB+): calcd. for C40H48NaO8 [M + Na]
679.3247; found 679.3262.
ν = 2926, 2854, 1739, 1230, 1093 cm–1. [α]D
=
0.0 (c = 0.20,
˜
General Procedure for the Esterification of Alcohols 16–18 with
(R)-12-Hydroxystearic Acid. Synthesis of Esters 19–21.
(E,2S,3S,4R,7R,8S,9S,12ЈR)-2,3,4,7,8,9-Hexa(benzyloxy)-10-hy-
droxydec-5-enyl 12-Hydroxystearate (19). Preparation of the Acti-
vated Anhydride: 2,4,6-Trichlorobenzoyl chloride (51.5 µL,
0.329 mmol) was added to a solution of (R)-12-hydroxystearic acid
(99 mg, 0.329 mmol) and Et3N (50 µL, 0.362 mmol) in THF
(2.5 mL). The reaction mixture was allowed to stir for 20 h, and
was then filtered through a small plug of cotton wool and evapo-
rated to give 167 mg of a white powder. This was dissolved in
CH2Cl2 (10.8 mL) to give a 15.4 mg/mL standard solution.
CH2Cl2). HRMS (FAB+): calcd. for C60H82NaO12 [M + Na]
1017.5704; found 1017.5705.
(E,2S,3S,4R,7R,8S,9S,12ЈR)-2,3,8,9-Tetra(benzyloxy)-10-hydroxy-
4,7-dimethoxydec-5-enyl 12-Hydroxystearate (21): This compound
was prepared from 18 as described for 19 and obtained in 82%
yield together with 84 % of unreacted alcohol 18. 1H NMR
(400 MHz, CDCl3): δ = 7.38–7.19 (m, 20 H), 5.72 (dd, J = 15.9,
6.8 Hz, 1 H), 5.66 (dd, J = 15.9, 7.1 Hz, 1 H), 4.73–4.49 (m, 8 H),
4.33 (dd, J = 11.8, 4.0 Hz, 1 H), 4.20 (dd, J = 11.8, 6.3 Hz, 1 H),
3.86–3.72 (m, 4 H), 3.69–3.56 (m, 3 H), 3.54 (dd, J = 5.8, 4.0 Hz,
1 H), 3.45 (t, J = 4.8 Hz, 1 H), 3.24 (s, 6 H), 2.33 (s, 2 H), 2.23 (t,
J = 7.6 Hz, 2 H), 1.67–1.50 (m, 2 H), 1.50–1.35 (m, 6 H), 1.35–
1.19 (m, 20 H), 0.88 (t, J = 6.5 Hz, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 173.6, 138.3, 138.23, 138.17, 138.1, 131.6, 131.1,
128.43, 128.37, 128.35, 128.30, 128.25, 128.0, 127.9, 127.81, 127.77,
127.7, 81.71, 81.69, 81.5, 81.0, 79.6, 77.4, 74.70, 74.68, 73.00, 72.7,
72.0, 63.8, 61.4, 56.8, 56.7, 37.50, 37.48, 34.3, 31.8, 29.7, 29.60,
29.55, 29.5, 29.4, 29.3, 29.2, 25.7, 25.6, 24.9, 22.6, 14.1 ppm; the
two missing aromatic carbon signals are overlapping with the sig-
Esterification: Alcohol 16 (192 mg, 0.237 mmol) and DMAP
(5.8 mg, 0.0475 mmol) were dissolved in CH2Cl2 (20 mL). To this
solution was added 1.5 mL of the standard solution prepared
above, and the reaction mixture was left stirring overnight. HCl
(0.25 , 10 mL) was added to quench the reaction and the phases
were separated. The organic layer was collected, dried (MgSO4),
and evaporated to give a mixture of the title compound and unre-
acted starting material. This mixture was separated by flash
chromatography (pentane/EtOAc, 4:1Ǟ 1:1) to give 19 in 73%
yield (36.4 mg, 0.0334 mmol) together with 74 % of recovered
nals at δ = 127–129 ppm. IR (neat): ν = 2929, 2854, 1736, 1456,
˜
1092 cm–1. [α]D = –8.7 (c = 0.15, CH2Cl2). HRMS (FAB+): calcd.
1
alcohol 16. H NMR (400 MHz, CDCl3): δ = 7.30–7.20 (m, 30 H),
for C58H82NaO10 [M + Na] 961.5806; found 961.5807.
5.76 (dd, J = 15.9, 6.5 Hz, 1 H), 5.72 (dd, J = 15.9, 6.5 Hz, 1 H),
4.70 (d, J = 11.6 Hz, 1 H), 4.66–4.51 (m, 8 H), 4.48 (d, J = 11.6 Hz, (E,2S,3S,4R,7R,8S,9S,12ЈR)-2,3,4,7,8,9,10-Heptahydroxydec-5-enyl
1 H), 4.36 (d, J = 11.8 Hz, 1 H), 4.32 (d, J = 11.8 Hz, 1 H), 4.22
(dd, J = 11.7, 4.5 Hz, 1 H), 4.16 (dd, J = 11.7, 6.0 Hz, 1 H), 4.10
12-Hydroxystearate (10): Surfactant precursor 19 (64 mg,
0.0586 mmol) was dissolved in MeOH (15 mL) and Pd/C (10 wt.-
(t, J = 6.2 Hz, 1 H), 4.07–4.01 (m, 1 H), 3.77 (app. q, J = 5.0 Hz, %, 25 mg) was added. The mixture was degassed at –78 °C for
1 H), 3.65 (s, 1 H), 3.60–3.48 (m, 5 H), 2.24–2.16 (m, 1 H), 2.15 (t, 30 min, and then connected to a H2 gas balloon. The reaction mix-
J = 7.6 Hz, 2 H), 1.58 (s, 1 H), 1.55–1.46 (m, 2 H), 1.45–1.33 (m,
ture was hydrogenated at room temp. for 24 h. The H2 gas balloon
was then disconnected from the flask and the catalyst was removed
6 H) 1.32–1.17 (m, 20 H), 0.86 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 173.5, 138.4, 138.20, 138.19, 138.0, 137.8, by filtration through a small plug of RP silica, and washed with a
131.5, 131.3, 128.43, 128.38, 128.37, 128.35, 128.32, 128.28, 128.27, few milliliters of fresh MeOH. Concentration of the filtrate and
128.22, 127.91, 127.86, 127.81, 127.76, 127.70, 127.68, 127.62, 81.7, crystallization of the remaining powder from water gave the desired
80.9, 79.8, 79.6, 79.4, 74.8, 74.7, 72.9, 72.7, 72.0, 70.94, 70.93, 63.5, surfactant 10 in 61 % yield (20 mg, 0.0354 mmol). 1H NMR
61.4, 37.50, 37.49, 34.2, 31.8, 29.7, 29.6, 29.5, 29.44, 29.37, 29.27,
29.2, 25.7, 25.6, 24.9, 22.6, 14.1 ppm; one missing carbon signal is
overlapping with the signals present at δ = 137–139 ppm, three
missing carbon signals are overlapping with the signals present at
δ = 127–129 ppm, and one benzylic carbon signal is overlapping
(400 MHz, MeOD): δ = 4.15–3.99 (m, 2 H), 3.88–3.78 (m, 1 H),
3.67–3.46 (m, 5 H), 3.44–3.34 (m, 2 H), 3.32 (t, J = 4.0 Hz, 1 H),
2.26 (t, J = 7.3 Hz, 2 H), 1.64–1.44 (m, 6 H), 1.41–1.11 (m, 26 H),
0.81 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
175.5, 74.6, 74.4, 74.0, 73.3, 73.1, 72.5, 71.5, 66.9, 64.4, 38.4, 35.0,
33.1, 30.9, 30.8, 30.7, 30.61, 30.58, 30.4, 30.2, 26.8, 26.0, 23.7,
14.4 ppm; two missing carbon signals are overlapping with the sig-
nals at δ = 30–31 ppm, two signals are overlapping at δ = 38.4 ppm,
with the signals present at δ = 70–76 ppm. IR (neat): ν = 2926,
˜
1736, 1454, 1095, 733, 698 cm–1. [α]D = +3.1 (c = 0.16, CH2Cl2).
HRMS (FAB+): calcd. for C70H90NaO10 [M + Na] 1113.6432;
found 1113.6445.
and two signals are overlapping at δ = 26.8 ppm. IR (neat): ν =
˜
984
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Eur. J. Org. Chem. 2006, 978–985

Polyhydroxylated Compounds as Head Groups in Surfactant Synthesis
FULL PAPER
3340 cm–1 (br), 2920, 2850, 1730 cm–1. [α]D = +4.8 (c = 0.98,
CH2Cl2). HRMS (FAB+): calcd. for C28H56NaO10 [M + Na]
575.3771; found 575.3773.
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Received: August 11, 2005
Published Online: December 5, 2005
Eur. J. Org. Chem. 2006, 978–985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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