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Synlett 2013; 24(2): 201-206
DOI: 10.1055/s-0032-1317929
letter
© Georg Thieme Verlag Stuttgart · New York

Versatile Synthesis of Amphiphilic Oligo(Aliphatic-Glycerol) Layer-Block Dendrons with Different Hydrophilic-Lipophilic Balance Values

Lai-Sheung Choi
a   Department of Chemistry, and State Key Laboratory of Synthetic Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
,
Hak-Fun Chow*
a   Department of Chemistry, and State Key Laboratory of Synthetic Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
b   Institute of Molecular Functional Materials, UGC-AoE Scheme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR   Fax: +85226035057   Email: hfchow@cuhk.edu.hk
› Author Affiliations
Further Information

Publication History

Received: 05 November 2012

Accepted: 27 November 2012

Publication Date:
13 December 2012 (online)

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Abstract

A series of amphiphilic oligo(glycerol-aliphatic) layer-blocked dendrons with different hydrophilic-lipophilic balance values (3.5–15.0) was prepared for use in controlled drug delivery and self-assembly studies. The synthetic strategies involved first a convergent growth of the inner hydrophobic sector followed by a divergent growth of the outer hydrophilic sector.

Key words

dendrimers - dihydroxylation - Mitsunobu reaction

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 1 Wang Y, Grayson SM. Adv. Drug Delivery Rev. 2012; 64: 852
    CrossrefSearch in Google Scholar
  • 2 Pan Y, Ford WT. Macromolecules 2000; 33: 3731
    CrossrefSearch in Google Scholar
  • 3 Newkome GR, Moorefield CN, Baker GR, Saunders MJ, Grossman SH. Angew. Chem., Int. Ed. Engl. 1991; 30: 1178
    CrossrefSearch in Google Scholar
  • 4 Lee J.-J, Ford WT, Moore JA, Li Y. Macromolecules 1994; 27: 4632
    CrossrefSearch in Google Scholar
  • 5 Cho B.-K, Jain A, Nieberle J, Mahajan S, Wiesner U, Gruner SM, Türk S, Räder HJ. Macromolecules 2004; 37: 4227
    CrossrefSearch in Google Scholar
  • 6 Svenson S, Tomalia DA. Adv. Drug Delivery Rev. 2012; in press; doi: 10.1016/j.addr.2012.09.030
  • 7 Padias AB, Hall HK. Jr, Tomalia DA, McConnell JR. J. Org. Chem. 1987; 52: 5305
    CrossrefSearch in Google Scholar
    • 8a Jayaraman M, Fréchet JM. J. J. Am. Chem. Soc. 1998; 120: 12996
      CrossrefSearch in Google Scholar
    • 8b Grayson SM, Jayaraman M, Fréchet JM. J. Chem. Commun. 1999; 1329
  • 10 Newkome GR, Moorefield CN, Baker GR, Johnson AL, Behera RK. Angew. Chem. Int. Ed. Engl. 1991; 30: 1176
    CrossrefSearch in Google Scholar
  • 11 Shi Z.-F, Chai W.-Y, An P, Cao X.-P. Org. Lett. 2009; 11: 4394
    CrossrefSearch in Google Scholar
  • 14 Ouchi M, Inoue Y, Wada K, Iketani S.-i, Hakushi T, Weber E. J. Org. Chem. 1987; 52: 2420
    CrossrefSearch in Google Scholar
  • 15 The structural properties of all compounds were characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and/or elemental analysis. Their good purities were also confirmed by a polydispersity index of <1.02 by size-exclusion chromatographic analysis.
  • 16 See the Supporting Information for details.
  • 17 Synthesis of 19: A solution of DIAD (0.53 mL, 2.67 mmol) in toluene (6 mL) was added dropwise to a stirred solution of allylic alcohol 18 (1.78 g, 2.06 mmol), Ph3P (0.70 g, 2.67 mmol), and Meldrum’s acid (0.15 g, 1.03 mmol) in toluene (6 mL) at –10 °C. The progress of the reaction was monitored by TLC. When the reaction was complete (ca. 30 min), hexane (30 mL) was added to the mixture to precipitate Ph3PO, which was removed by filtration. The excess solvent was removed and the yellow residue was purified by flash column chromatography on silica gel (hexane–EtOAc, 3:1→1:1, in the presence of 1% Et3N) to afford the target compound 19 (0.76 g, 40%) as a colorless oil. Rf = 0.54 (hexane–acetone, 2:1); 1H NMR (300 MHz, CDCl3): δ = 0.91 (s, 24 H, CH2CCH 3), 1.00–1.50 (m, 76 H), 1.38 (s, 24 H, OCCH3), 1.39 (s, 24 H, OCCH3), 1.64 (s, 6 H, CO2CCH3), 1.78–1.95 (m, 2 H, CHC=C), 2.66 (d, J = 6.9 Hz, 4 H, CH2C=C), 3.45 (AB system, J = 11.4 Hz, 16 H, COCHH), 3.55 (AB system, J = 11.4 Hz, 16 H, COCHH), 5.20 (dt, J = 15.3, 7.2 Hz, 2 H, CH2CH=CH), 5.36 (dd, J = 15.0, 8.4 Hz, 2 H, CH2CH=CH); 13C NMR (75 MHz, CDCl3): δ = 19.8, 20.2, 23.7, 24.1, 24.5, 30.2, 32.7, 34.0, 34.5, 34.6, 35.6, 36.0, 37.4, 42.7, 43.1, 56.1, 69.6, 97.9, 105.3, 121.8, 142.3, 168.8; MS (FAB): m/z (%) = 1823 (100) [M – CH3 +]; HRMS (FAB): m/z calcd for (C110H196O20 – CH3)+: 1822.4080; found: 1822.4113.
  • 18 Synthesis of G[2+2]-(OH)32(OBn) 1: OsO4 (2.5 wt% in t-BuOH, 0.44 mL, 0.044 mmol) was added dropwise to a solution of 16-ene 32 (873 mg, 0.44 mmol) and NMO (1.23 g, 10.46 mmol) in acetone–H2O (20 mL, 10:1, v/v) at 0 °C. The mixture was stirred at 20 °C for 48 h and the progress of the reaction was monitored by NMR analysis until all allyl groups had reacted. The solvent was removed in vacuo and the dark-brown residue was purified by membrane dialysis in MeOH using regenerated cellulose (MWCO = 1,000) to give the target compound 1 (1.02 g, 92%) as a viscous brown liquid. Rf = 0.08 (EtOAc–MeOH, 1:3); 1H NMR (300 MHz, DMSO-d 6): δ = 0.78 (s, 12 H, CH3), 0.92–1.45 (m, 38 H), 1.45–1.61 (m, 1 H, CHCH2OBn), 3.00–3.23 (m, 16 H, CH3CCHHO), 3.23–3.46 (m, 90 H, OCHCH 2O and CHCH 2OBn), 3.46–3.68 (m, 32 H, OCHCH 2O), 4.42 (t, J = 5.7 Hz, 10 H, OH and PhCH2O), 4.47 (t, J = 5.7 Hz, 8 H, OH), 4.51 (t, J = 4.8 Hz, 8 H, OH), 4.60 (dd, J = 4.8, 1.2 Hz, 8 H, OH), 7.16–7.45 (m, 5 H, ArH); 13C NMR (75 MHz, DMSO-d 6): δ = 19.6, 20.0, 23.4, 31.8, 33.7, 34.6, 35.1, 36.8, 37.8, 38.7, 63.4, 63.5, 70.7, 70.9, 71.0, 71.3, 71.89, 71.93, 72.4, 73.1, 75.5, 78.1, 127.6, 127.8, 128.4, 139.0; HRMS (MALDI-TOF): m/z calcd for (C117H228O57 + Na)+: 2569.4869; found: 2569.4974.