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Lactosylceramides with Unsaturated Fatty AcidsЧSynthesis and Use in the Generation of Bilayer Membranes.

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(41 Cf.. e g.: W. Lubitz, M. Plato, K. Mobius, D. Biehl, J . Phys. Chert. 83
(1979) 3401 ; H. Kurreck. B. Kirste, W. Lubitz, Angew. Chem. 96 (1984)
171: Angew. Chem. Int. Ed. Engl. 23 (1984) 173, and references cited
therein. ESR investigations of semiquinone ion pairs have been reported,
for example. by E. A. C. Lucken, J . Chem. SOC.1964. 4234; N. Hirota in
E. T. Kaiser, L. Kevan (Eds.): Radical Ions. Wiley-Interscience, New
York 1968, p. 35f; T. E. Cough, P. R. Hindle, Can. J. Chem. 47(1969)
1698. 3393.
151 For summaries of investigations on ion pairs from various view points
see. e.g. a) J. M. Masnovi, J. Kochi, J. Am Chem. Soc. 107(1985) 7881; b)
E. S Gould, Acc. Chem. Res. 18 (1985) 22; c) W. Kaim, ibid. 18 (1985)
160: d) A. Streitwieser, Jr., ibid. 17 (1984); e) J. M. Lehn, Pure Appl. Chem.
52 (1980) 2303: t) A. Kaifer, D. A. Gustowski, L. Echegoyen, V. J. Gatto,
R. A. Schultz, T. P. Cleary, C. R. Mor, D. M. Goli, A. M. Rios, G. W.
Gokel. J . Am. Chem. Soc. 107 (1985) 1958, and references cited therein.
Cf. also (41.
[6] Reducible chelate molecules with 0- or N-docking sites have already
been used repeatedly for ESR/ENDOR investigations on radical ion
pairs. Examples are a) crown ethers with reducible x systems such as quinones (cf. [I]); b) orrho-quinones (cf. e.g.: J. A. Pedersen, CRC Handbook
of EPR Spectra from Quinols. CRC Press, Boca Raton, FL, USA 1985 or
[2]); c) semidiones (cf. e.g.: G. A. Russell, C. E. Osuch, J. Am. Chem. SOC.
100 (1984) 5979 or [4]); d) N-heterocycles such as a,a'-bipyridyl (cf. e.g.:
W. Kaim, J . Am. Chem. SOC.104 (1982) 3833, and references cited therein).
(71 I-Aminosemianthraquinone radical anion with nBu4Ne as, largely interaction-free. countercation can be generated electrochemically in THF/
TBAP solution. THF is chosen as solvent for the ESR investigations because it favors the formation of contact ion pairs relative to more polar
solvents such as DMF (cf. e.g.: K. A. M. Greber, K. S. Chen, J. K. S.
Wan, Rev. Chem. Intermed. 5 (1984) 37; E. Lesniewska-Lada, M. K. Kalinowski. Electrochim. Acta 28 (1983) 1415, and references cited therein).
The radical ion pairs [M0Qo'lo are prepared in THF by reduction of
I-aminoanthraquinone on the respective alkali metal mirrors; for the preparation of Rb- and Cs-mirrors, the thermal decomposition of their
azides in the presence of fine-grained iron powder proved to be advantageous. The ENDOR measurements were carried out with a Bruker
220 D spectrometer; with magnetic fields of about 3.4 kG, the frequencies
6, of the individual isotopes are (rel. abundance): ' H 14.46 MHz
(99.98%). 'Li 5.62 MHz (92.6%), "Na 3.82 MHz (lOO%), "Rb 4.73 MHz
(27%) and '"Cs 1.90 MHz (l0Ooh).
(81 a) H. McConnell, J . Chem. Phys. 24 (1956) 632; b) cf. e.g.: J. Bolton, J.
Wertz, Electron Spin Resonance- Elementary Theory and Applications.
McGraw-Hill. New York 1972.
while considerable amounts of the Cz0 homologues are
found in the gangliosides of the brain. Unsubstituted and
a-hydroxy fatty acids are met as N-acyl groups which can
contain double bonds.[21
Bilayer membranes could not be obtained with the glycosphingolipids thus far available, which are mostly chemically heterogeneous. Recently, we developed a synthetic
method with which pure glycosphinolipids can be prepared in good yields.'31Since the fatty acid is coupled with
the amino group of the sphingosine moiety in the last reaction step, this synthetic method is also suitable for systems
with sensitive acids. We have now used it for the synthesis
of lactosyl sphingolipids containing unsaturated fatty
acids which promote membrane formation and membrane
fluidity.'*' Reaction of 0-acetylated 0-(a-lactosyl) trichloroa~etimidate[~]
as donor and 3-0-benzoylated azidosphingosine[" as acceptor with BF3-OEt2 as catalyst afforded
the glycoside 1[71
(yield 85%). Competing formation of ortho ester could be completely suppressed by successive addition of 0.05 equivalents of catalyst. Deacylation with sodium methoxide/methanol furnished 2 in quantitative
yield, and reduction of the azide group with H2S/pyridine
afforded the lactopsychosine 3, which has already been
prepared via another route.[31The acid chlorides, which
were generated with oxalyl chloride, proved to be the best
for the coupling of oleic, linolic, linolenic, and arachidonic
acids. Their reaction with 3 in the presence of sodium acetate in tetrahydrofuran (THF)/water led in good yields
(65-74%) to the lactosylceramides 4-7.I7l These can be obtained pure by peracetylation and subsequent deacetylation with Florisil[81(4,5), or directly by reversed phase
chromatography (6,7 ; RP,,,''] n-butanol/methanol/water,
50 :32 : 18)."l
Lactosylceramides with Unsaturated Fatty AcidsSynthesis and Use in the Generation of
Bilayer Membranes**
1: X = Ng. R = Ac. R' = BZ
2: X = N3, R = R' = H
3: X = NH,. R = R' = H
By Richard R . Schmidt.* Thomas Bar, and
Hans-Juergen Apell
Dedicated to Professor Wolfgang PJeiderer on the
occasion of his 60th birthday
Glycosphingolipids are membrane building blocks,
which, with their lipid moiety, the N-acylated sphingosine
( = ceramide), participate in the formation of the outer
plasma membrane bilayer. The hydrophilic carbohydrate
moiety is located on the outer membrane surface, and thus
can determine the specificity of interactions with cells and
various biofactors."' C,,-sphingosine is the most important
sphingosine base in the majority of mammalian tissues,
5 : C-R"
Angew Chem. Int. Ed. Engl. 26 11987) No. 8
Fakultat fur Chemie der Universitat
Postfach 5560, D-7750 Konstanz (FRG)
Dr. H.-J. Apell
Fakultat fur Biologie der Universitat
Postfach 5560, D-7750 Konstanz (FRG)
Glycosyl Imidates, Part 30. This work was supported by the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We
thank Prof. Dr. P. Luuger, Konstanz, for valuable discussions.-Part 29:
R. R. Schmidt, G Effenberger. Liebigs Ann. Chem., in press.
4: C-R"
7 : C-R"
T. Bar
6 : C-R"
['I Prof. Dr R. R. Schmidt, DipLChem.
-= 1
_ - - -
To gain insights into the complexity of the cell membranes it is essential first of all to investigate the properties
and modes of reaction of the individual membrane components in simple models.191We have therefore generated bilayer membranes with the glycosphingolipids 4-7 using
and have deterthe bilayer technique of Miiller et al.19.'n1
0 VCH Verlagsgesellschafr mbH. 0-6940 Weinheim. 1987
0570-0833/87/0808-0793 S 02.50/0
mined the thickness of the membranes from measurements
of the electrical capacity on “black films” (black bilayer
membranes BLM).“’.”l Bilayer membranes with remarkable longevity (up to several hours) and stability toward
higher potentials (measurements u p to 300 mv) could be
obtained (surface areas 0.15 mm’) from 3-4% solutions of
4 - 7 in n-decane/n-butanol (100 : 1). The specific membrane capacities measured at potentials of 10-300 mV (Table 1) lie about a factor of 1.5 above those of phosphatidylTable I . Specific membrane capacity (C,) and thickness ( d ) of the hydrocarbon region of the bilayer membranes of lactosylceramides 4 - 7 [a].
C , [pF/cm’] [b]
d Inml Icl
0.563 t 0 . 0 7 2
0.755 kn.073
0.8 I8 t0.092
2.46 t0.25
2.27 0.20
3 . 2 6 t 0.49
[lo] P. Miiller, D. 0. Rudin, H. T. Tien, W. C. Wescott, Nature London 194
(1962) 979.
[ I I ] P. Lauger, W. Lesslauer, E. Marti, J. Richter, Biochim. Biophys. Acfu 135
(1967) 20.
1121 R. Benz, 0. Frohlich, P. Lauger, M. Montal, Biochim. Biophys. Acfu 394
(1975) 323; R. Benz, K. Janko, rbid. 455 (1976) 721. Specific membrane
capacities of various phospholipids are presented in this publication.
Deep-Colored, Through-Conjugated
Multitriphenylmethylium Ions**
By Dieter Hellwinkel.* Heinz Stahl, and
Heinrich Ceorg Gaa
[a] For details of the measurements see Refs. [9-121 and literature cited therein. [b] Mean value of ten measurements. [c] For calculation see Ref. [ I I].
Monocationic “conventional” triphenylmethylium dyes
of the crystal violet type 1 and the tricationic “inverse”
analogues 2 derivable from them by exchanging the functionalities show almost the same longest-wavelength absorptions in the electronic spectrum and have virtually the
same green color.“]
choline membranes.l’21 This can be due to the altered dielectric properties of the hydrophilic head groups in the case
of the lactosylceramides, or to the bilayer being thinner
due to tighter coiling and kinking of the lipid moiety. The
specific membrane capacities increase with the increasing
number of cis double bonds in the C,,-acid derivatives 46, whereas, conversely, the estimated layer thickness for
the lipid moiety, presumably determined by the kinking,
decreases. The specific membrane capacity of the arachidonic acid derivative 7 is of the same order of magnitude
as that of the oleic acid derivative 4, i.e. the chain lengthening by two C-atoms is balanced out by about three additional cis double bonds.
Received: April 6, 1987 [Z 2180 IE]
German version: Angew. Chem. 99 (1987) 813
[ I ] R. R. Schmidt, Angew. Chem. 98 (1986) 213; Angew. Chem. Int. Ed.
Engl. 25 (1986) 212; R. R. Schmidt in W. Bartmann, K. B. Sharpless
(Hrsg.): Stereochemistry of Organic und Bioorganic Trunsformafions.
VCH Verlagsgesellschaft. Weinheim 1987, p. 169, and references cited
[2] N. K. Kochetkov, G. P. Smirnova, Adv. Curbohydr. Chem. Biochem. 44
(1986) 387, and references cited therein.
[3] R. R. Schmidt, P. Zimmermann, Angew. Chem. 98 (1986) 722; Angew.
Chem. Inf. Ed. Engl. 25 (1986) 725.
[4] A. K. Akimoto, L. Dorn, H. Gros, H. Ringsdorf, H. Schupp, Angew.
Chem. 93 (1981) 108; Angew. Chem. Int. Ed. Engl. 20 (1981) 90.
[ 5 ] R. R. Schmidt, J . Michel, M. Roos, Liebigs Ann. Chem. 1984. 1343: J .
Michel, Dissertation. Universitat Konstanz 1983.
[6] R. R. Schmidt, P. Zimmermann, Tefruhedron Letr. 27 (1986) 481.
171 ’H-NMR: I (250 MHz, CDCI,, TMS): 6=7.42-8.06 (m, 5 H, Bz), 5.855.96 (m. I H, CHI-CH=), 5.48-5.65 (m, 2 H , =CH-CH-OBz), 5.35 (d,
I H , H-4’, J = 2 . 7 Hz), 5.07-5.23 (m, 2H), 4.89-4.98 (m,2H). 4.45-4.53
(m, 3 H), 4.02-4.12 (m, 3 H), 3.79-3.97 (m, 4H). 3.54-3.65 (m, 2 H), 1.962.20 (m, 23H, 7Ac, =CH-CH2), 1.24-1.37 (m, 22H, I l C H > ) , 0.88 (1,
3 H , C H 4 - 4 (250 MHz, [D,]Dimethyl sulfoxide, TMS): S=7.54 (d,
I H, NH, 5=8.8 Hz), 5.49-5.57 (m, I H, =CH-CH2), 5.30-5.39 (m. 3 H,
=CH-CHOH, CH=CH), 5.16 (d, I H, OH, J=3.7 Hz), 5.12 (d, I H, OH,
J = 3 . 3 Hz),4.90(d, I H , O H , J = 5 . 5 Hz),4.84(d, I H , O H , 5 ~ 3 . 1Hz),
4.68 (very broad, 2H, ZOH), 4.58 (m, 2H, 2 0 H ) , 3.29-4.22 (m,17H).
3.02-3.09 (m, 1 H), 1.96-2.06 (m, 8 H , COCH?, 3 =CH-CHZ), 1.23-1.48
(m. 44H, 22CHz), 0.83-0.91 (2t, 6 H , 2CH,). The compounds 5 - 7 also
gave correct ‘H-NMR data.-The UV spectroscopically determined
amounts of fatty acid esters with conjugated double bonds are: < 1% for
6 and <3% for 7.
[8] Florisil (magnesium silicate), 16-30 mesh, Fluka AG; RP,,, Merck.
[9] P. LBuger, Angew. Chem. 97 (1985) 939: Angew. Chem. I n f . Ed. Engl. 24
(1985) 905.
0 VCH Verlagsgesellschaft mbH. 0-6940 Weinheim, 1987
(in CHC
, OH
(Lge): 627 (4.95)
641 (5.26)
409 (3.27)
426 (4.35)
5% CF,CO,H)
(in CF3C0,H)
This can be readily explained with the aid of the characteristic HMO frontier orbital scheme for the alternating
structural types shown above. The scheme is characterized
by two non-bonding (n) orbitals and the weakly bonding
and antibonding molecular orbitals b, a, respectively, of
opposite but equal energies (Fig. I).
a (-0.28)
- “(0.00)
Fig. 1. Frontier orbital occupancy scheme for conventional triphenylmethylium ions 1 a n d their tricationic “inverse” analogues 2 in the Huckel approximation (energies in @units).
Prof. Dr. D. Hellwinkel, DipLChem. H. Stahl, DipLChem. H. G. Gaa
Organisch-chemisches lnstitut der Universitat
Im Neuenheimer Feld 270, D-6900 Heidelberg I (FRG)
[**I This work was supported by the Deutsche Forschungsgemeinschaft, the
Fonds der Chemischen Industrie, and by BASF AG.
0044-8249/87/0808-0794 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 26 (1987) No. 8
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generation, lactosylceramides, unsaturated, acidsчsynthesis, membranes, fatty, use, bilayers
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