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Synlett 2002(9): 1467-1470
DOI: 10.1055/s-2002-33504
LETTER
© Georg Thieme Verlag Stuttgart · New York

Convergent Synthesis of Antiparallel Cyclobolaphiles Having Two Diacetyl-enes: Mimetics of Membrane Components That are Found in Archaea

Kazuhiro Miyawaki, Rie Goto, Toshiyuki Takagi, Motonari Shibakami*
Institute for Materials and Chemical Process, Institute of Advanced Industrial Science and Technology (AIST), Central 5th, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
Fax: +81(298)614547; e-Mail: moto.shibakami@aist.go.jp;
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Publication History

Received 5 July 2002
Publication Date:
17 September 2002 (online)

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Abstract

Chiral 48-membered antiparallel cyclobolaphiles and their diastereomer having two diacetylenes were convergently synthesized utilizing both cross-coupling method (CuI, pyrrolidine) and Glaser intramolecular cyclization, starting from commercially available d- and l-1,2-O-isopropylidene-sn-glycerol as chiral sources.

Key words

caldarchaeol - diacetylene - antiparallel cyclobolaphile - convergent synthesis - mimetics

    References

  • 1a

    We term caldarchaeol with a parallel arrangement of glycerol units ‘parallel caldarchaeol’, and that with an antiparallel arrangement ‘antiparallel caldarchaeol’.
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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’.

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).

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.

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.