Efficient Synthesis of Parallel Cyclobolaphiles Having Two Diacetylenes: Mimetics of Archaeal Membrane Lipids

Abstract

Chiral 48-membered parallel cyclobolaphiles and their diastereomer having two diacetylenes were efficiently synthesized by utilizing both the selective deprotection and the cross-coupling method of two distinct acetylenic compounds.

Key words

archaeal lipid - diacetylene - chirality - parallel cyclo­bolaphile - mimetics

References

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• 4c

  While amphiphiles having a macrocyclic ring as a hydrophobic segment have been termed ‘macrocyclic bolaamphiphiles’ (see Ref. [2a] ), we prefer to adopt the abbreviated and more readily pronounceable term, ‘cyclobolaphile’.

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6

Intense examination of macrocyclic synthetic methods that have been previously reported indicates that only our strategy has the potential to provide three stereoisomers of parallel cyclobolaphiles that contain diacetylene units (see Ref. [1c] [d] [2] ).

11

All new compounds gave satisfactory analytical and spectral data. Selected physical data are as follows: 4: Stage yellow oil, R_f = 0.55 [hexane/ethyl acetate (2:1, v/v)], [α]_D ²⁸ -1.67 (c 0.24, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.45-7.39 (m, 12 H), 7.27-7.19 (m, 18 H), 7.16 (d, J = 8.8 Hz, 4 H), 6.81 (d, J = 8.5 Hz, 4 H), 4.44 (d, J = 11.6 Hz, 2 H), 4.40 (d, J = 11.9 Hz, 2 H), 3.77 (s, 6 H), 3.56-3.49 (m, 10 H), 3.17 (d, J = 4.6 Hz, 4 H), 2.19 (t, J = 7.2 Hz, 4 H), 1.56-1.44 (m, 8 H), 1.34-1.24 (m, 16 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 159.06, 144.09, 130.48, 129.13, 128.72, 127.70, 126.87, 113.62, 86.48, 78.29, 77.52, 72.87, 70.60, 70.09, 65.22, 63.44, 55.24, 30.06, 29.33, 29.07, 28.82, 28.32, 26.10, 19.17 ppm. Anal. Calcd for C₈₀H₉₀O₈: C, 81.46; H, 7.69%. Found: C, 81.43; H, 7.66%. 8: Stage pale yellow oil, R_f = 0.13 [hexane/ethyl acetate (2:1, v/v)], [α]_D ²⁸ -9.80 (c 0.60, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 3.72-3.48 (m, 18 H), 2.23 (t, J = 6.9 Hz, 8 H), 2.17 (brs, 2 H), 1.65-1.42 (m, 16 H), 1.40-1.19 (m, 32 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 78.44, 77.41, 71.60, 71.08, 70.34, 65.31, 62.90, 29.95, 29.46, 29.26, 29.10, 28.93, 28.58, 28.19, 25.93, 19.11 ppm. LRMS (FAB): m/z = 725 [(M + H)⁺]. Anal. Calcd for C₄₆H₇₆O₆: C, 76.20; H, 10.56%. Found: C, 76.19; H, 10.81%. 10: [α]_D ²⁸ +9.67 (c 0.30, CHCl₃). 15: [α]_D ²⁸ 0.00 (c 0.45, CHCl₃). (2R,27R)-1: Stage pale yellow solid, R_f = 0.1 [CHCl₃/MeOH/H₂O (65:25:4, v/v/v)]. [α]_D ²⁸ +5.81 (c 0.75, MeOH). ¹H NMR [500 MHz, CDCl₃/CD₃OD (97:3, v/v)]: δ = 4.24 (brs, 4 H), 3.84 (t, J = 5.3 Hz, 4 H), 3.65 (brs, 4 H), 3.58-3.51 (m, 8 H), 3.43-3.37 (m, 6 H), 3.24 (s, 18 H), 2.21 (t, J = 6.7 Hz, 8 H), 1.49-1.43 (m, 16 H), 1.34-1.20 (m, 32 H) ppm. ¹³C NMR (125 MHz, CD₃OD):
δ = 79.50, 77.97, 72.46, 72.01, 71.49, 67.47, 66.57, 66.20, 60.37, 54.69, 31.21, 30.78, 30.41, 30.24, 29.98, 29.83, 29.58, 27.29, 19.79 ppm. ³¹P NMR [200 MHz, CDCl₃/CD₃OD (99:1, v/v)]: δ = -0.50 (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, 61.59; H, 9.43; N, 2.56%. (2S,27S)-1: [α]_D ²⁸ -5.77 (c 0.70, MeOH). (2R,27S)-1: [α]_D ²⁸ +0.00 (c 0.37, MeOH). The spectral data of (2R,27S)-1 and (2S,27S)-1 were identical with those of (2R,27R)-1.