Design, Synthesis, and Self-Assembly of Parallel Cyclobolaphile that Contains Four Amide Groups as a Linkage between Polar Head Groups and Hydro­carbon Chain: A Mimetic of Archaeal Membrane Lipid

Abstract

Chiral 52-membered macrocyclic compound has been synthesized by utilizing intramolecular cyclization under Eglinton conditions [Cu(OAc)₂, pyridine]. Three structural features include: (i) two hydrocarbon chains containing diacetylene, (ii) a linkage that is composed of amide group, and (iii) two polar head groups. Self-assembly of this compound in a mixture of chloroform-methanol (1:1) produced organogel. Transmission electron micrograph revealed that UV-irradiated gel is featured by nanosize helicity.

Key words

archaeal lipid - diacetylene - mimetic - amide - helical ribbon - nanostructure - polymerization - organogel

References

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  Synthesis of 7: A solution of Cu(OAc)₂ (138 mg, 0.762 mmol) and pyridine (56 mL) was stirred at 120 °C. To the reaction was then added a solution of 6 (100 mg, 0.076 mmol) in pyridine (5 mL) over 4 h at 120 °C. After cooling to r.t., pyridine was removed under reduced pressure. The resulting solution was allowed to stand at 120 °C for 11 h before the reaction mixture was quenched with sat. citric acid (50 mL), and then extracted with CHCl₃ (300 mL × 2). The organic phase was washed with brine, dried (Na₂SO₄), and concentrated to give a residue. Purification of the residue was done by flash chromatography (SiO₂, CHCl₃-MeOH, 20:1) to give 55 mg (55%) of 7 as colorless solid.

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• 13a

  All new compounds gave satisfactory analytical and spectral data. Selected physical data are as follows. Compound 7: Stage colorless solid, [α]_D ²²+4.87 (c 1.80, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.63-7.60 (m, 8 H), 7.45-7.41 (m, 12 H), 6.27 (d, J = 7.6 Hz, 2 H), 5.93 (t, J = 5.5 Hz, 2 H), 4.10-4.00 (m, 2 H), 3.79 (dd, J = 10.3, 3.7 Hz, 2 H), 3.62-3.53 (m, 4 H), 3.33-3.29 (m, 2 H), 2.22 (t, J = 6.9 Hz, 8 H), 2.12-2.20 (m, 8 H), 1.60-1.43 (m, 16 H), 1.38-1.30 (m, 8 H), 1.29-1.20 (m, 24 H), 1.06 (s, 18 H) ppm. ¹³C NMR: δ = 174.53, 173.98, 135.54, 133.07, 132.74, 130.01, 127.92, 127.89, 77.43, 65.35, 63.59, 51.45, 41.94, 36.76, 36.60, 29.22, 29.18, 28.91, 28.76, 28.29, 26.90, 25.64, 25.59, 19.26, 19.17 ppm. LRMS (FAB): m/z = 1310 [M + H]⁺, 1252 [M - (CH₃)₃C]⁺. Compound 1: Stage colorless solid. ¹H NMR [500 MHz, CDCl₃/CD₃OD (1:1,
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14

Our synthetic scheme should provide optically pure compound 1. Our reason for this is 2-fold. First, the first step [8a] that can lead to racemization retained the stereochemical configuration of l-serine methyl ester hydrochloride {2: [α]_D ²¹ +4.99 (c 3.55, CHCl₃), Lit. [8a] [α]_D +4.7 (c 1.2, CHCl₃)}. Second, intermediates (2-7) and the desired product (1) do not include carbonyl group that can cause epimerization at the chiral center.