References
1a We
term caldarchaeol with a parallel arrangement of glycerol units ‘parallel
caldarchaeol’, and that with an antiparallel arrangement ‘antiparallel
caldarchaeol’.
1b
Nishihara M.
Morii H.
Koga Y.
J.
Biochem.
1987,
101:
1007
2
Gräther O.
Arigoni D.
J. Chem. Soc., Chem. Commun.
1995,
405
3
Arakawa K.
Eguchi T.
Kakinuma K.
Chem.
Lett.
2001,
440
4
Eguchi T.
Kano H.
Kakinuma K.
J.
Chem. Soc., Chem. Commun.
1996,
365
5a
Eguchi T.
Ibaragi K.
Kakinuma K.
J. Org. Chem.
1998,
63:
2689
5b
Menger FM.
Chen XY.
Tetrahedron Lett.
1996,
37:
323
5c
Patwarahan AP.
Thompson DH.
Org.
Lett.
1999,
1:
241
5d
Wang G.
Hollingsworth RI.
Langmuir
1999,
15:
3062
6 Our working hypothesis has been that
each stereochemical combination of parallel-antiparallel caldarchaeol
analogues provides a nanostructure with various degrees of thermo-stability,
and that some optimal combinations give a considerably thermostable
nanostructure that is robuster than the natural one. Our ultimate
goal is to find such optimal combinations. Note that the applicability
of Kakinuma’s strategy to the construction of all stereoisomers and
diacetylene-containing derivatives (see in text) remains unclear,
although they did not refer to such possibility (see ref. 4a and
5a). As a first step toward this goal, therefore, alternative strategy
that is applicable to the synthesis of all stereoisomers is required.
7 Amphiphilic molecules that contain
a polar head group at the end of a hydrophobic segment have been
termed; ‘bolaamphiphiles’ (Fuhrhop, J.-H.; Mathiewu,
J. Angew. Chem., Int. Ed. Engl. 1984, 23, 100) or ‘bolaphile’ (Jayasuriya,
N.; Bosak, S.; Regen, S. L. J. Am. Chem. Soc. 1990, 112, 5844).
While amphiphiles having a macrocyclic ring as a hydrophobic segment
have been termed ‘macro-cyclic bolaamphiphiles’ (see
Ref. 5b), we prefer to adopt the abbreviated and more readily pronounceable
term, ‘cyclobolaphile’.
8
Ladika M.
Fisk TE.
Wu WW.
Jons SD.
J. Am. Chem. Soc.
1994,
116:
12093
9 Intense examination of macrocyclic
synthetic methods that have been previously reported indicate that
only our strategy has the potential to provide antiparallel cyclobolaphiles
that contain diacetylene units (see ref. 5).
10
Qin D.
Byun H.
Bittman R.
J. Am. Chem.
Soc.
1999,
121:
662
11
Hirth G.
Barner R.
Helv. Chim. Acta
1982,
65:
1059
12
Carvalho JF.
Prestwich GD.
J. Org. Chem.
1984,
49:
1251
13
Alami M.
Ferri F.
Tetrahedron Lett.
1996,
37:
2763
14 A solution of the precursor of 13 (0.10 g, 0.10 mmol) in acetone (5 mL)
was added to a stirred solution of CuCl (0.20 g, 2.1 mmol) and TMEDA
(310 µL, 2.1 mmol) in p-xylene (36
mL) under oxygen over 7 h at 130 °C.
15
Oikawa Y.
Yoshioka T.
Yonemitsu O.
Tetrahedron
Lett.
1982,
23:
885
16
Hansen WJ.
Murari R.
Wedmid Y.
Baumann WJ.
Lipids
1982,
17:
453
17 (2R, 27R)-1, (2S, 27S)-1, and (2R,
27S)-1 were successfully purified by flash
chromatography (SiO2, CHCl3/MeOH/H2O,
65:25:4, v/v/v).
18 All new compounds gave satisfactory
analytical and spectral data. Selected physical data are as follows: 14: Stage pale yellow oil, Rf = 0.13 [hexane/ethyl
acetate (2:1, v/v)], [α]D
25 -9.0
(c 0.61, CHCl3). 1H
NMR (500 MHz, CDCl3): δ = 3.70-3.38
(m, 18 H), 2.23 (t, J = 6.9
Hz, 8 H), 2.17 (brs, 2 H), 1.60-1.43 (m, 16 H), 1.36-1.23
(m, 32 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 78.42,
72.40, 71.65, 71.11, 70.33, 65.32, 63.00, 29.97, 29.50, 29.30, 29.15,
28.98, 28.63, 28.22, 25.97, 19.16 ppm. LRMS (FAB): m/z = 725 [(M + H)+].
Anal. Calcd for C46H76O6: C, 76.20;
H, 10.56%. Found: C, 75.91; H, 10.41%. 17: [α]D
25 +7.8
(c 0.85, CHCl3). 20: [α]D
28 0.0
(c 0.50, CHCl3). The spectral
data of 17 and 20 were
identical with those of 14 except the optical
rotations. (2R, 27R)-1: Stage pale yellow solid, Rf = 0.10 [CHCl3/MeOH/H2O
(65:25:4, v/v/v)], [α]D
25 +4.2
(c 0.70, MeOH). 1H
NMR [500 MHz, CDCl3/CD3OD
(97:3, v/v)]: δ = 4.21 (brs,
4 H), 3.83 (brs, 4 H), 3.60 (brs, 4 H), 3.56-3.51 (m, 8 H),
3.43-3.33 (m, 6 H), 3.19 (s, 18 H), 2.19 (t, J = 6.7
Hz, 8 H), 1.47-1.42 (m, 16 H), 1.33-1.15 (m, 32
H) ppm. 13C NMR (125 MHz, CD3OD): δ = 79.50,
77.98, 72.50, 72.03, 71.43, 67.47, 66.60, 66.23, 60.38, 54.71, 31.13,
30.79, 30.62, 30.41, 30.26, 29.96, 29.86, 29.59, 29.52, 27.29, 19.82 ppm. 31P
NMR [200 MHz, CDCl3/CD3OD
(99:1, v/v)]:
δ = -0.69
(s)ppm. LRMS (FAB): m/z = 1054 [M+],
995
[(M - (Me)3N)+].
Anal. Calcd for C56H100N2O12P2·2
H2O: C, 61.63; H, 9.60; N, 2.57%. Found: C,
61.62; H, 9.50; N, 2.42%. (2S,27S)-1: [α]D
27 -4.9
(c 0.49, MeOH). (2R,27S)-1: [α]D
28 0.0
(c 0.70, MeOH). The spectral data of
(2R,27S)-1 and (2S,27S)-1 were identical
with those of (2R,27R)-1 except the optical rotations.
19 Multilamellar suspension for hs-DSC
measurement was prepared as follows. First, 1 mL of methanol solution
of (2S, 27S)-1 (4.7 mM) was transferred to a test tube. The methanol was
then evaporated under a stream of nitrogen, thereby leaving the
lipid as a thin film on the walls of the test tube. The remaining
solvent was removed by subjecting the lipid film to high vacuum
for at least 2 h. 3 mL of milli-Q water was added and the mixture
was sonicated for 1 h at 972 °C. Calorimetric measurement
was performed with a MC-2 differential scanning calorimeter purchased
from Microcal, Inc.
20
Fuhrhop J.-H.
Liman U.
Koesling V.
J.
Am. Chem. Soc.
1998,
110:
6840
21
Menger FM.
Chen XF.
Brocchini S.
Hopkins HP.
Hamilton D.
J.
Am. Chem. Soc.
1993,
115:
6600 .
The ‘untethered’ lipids are also archaeal membrane
lipid analogues, and include linear saturated long alkyl chains
that are connected to the glycerol backbone by means of ether linkage.
If one may take into account the ”dimer-like structure"
of the cyclobolaphiles, it seems reasonable to assume that (2S,27S)-1 is
comparable to the ”untethered" lipid with chains of 10
carbons. Menger et al. have reported the Tm values for the ‘untethered’ lipids
with chains of only 14-20 carbons, ranging from 26.9 to
66.5 °C in this report. Thus, we currently consider that
the introduction of cyclic structure and diacetylene units leads
to higher thermostability, although exact comparison between the cyclobolaphile
and 10-carbon ”untethered" lipid remains to be made
