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DOI: 10.1055/s-2008-1078020
Desymmetrisation of Biphenyl-Based Carbohydrate Receptors: A Nonbonding Pillar in One Corner of the Cage
Publication History
Publication Date:
31 July 2008 (online)
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Abstract
We report a new addition to the family of biphenyl-based carbohydrate receptors, derived by replacing one out of four isophthalamide (diamide) linkages with the corresponding diester. The alteration results in lower binding constants, perhaps reflecting the entropic penalty for lowering receptor symmetry. However, the synthesis allows access to many related host molecules, with potential for restoring and raising affinities and tuning selectivities.
Key words
carbohydrates - supramolecular chemistry - bioorganic chemistry - esters - biaryls
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References and Notes
3-Acetyloxymethyl-5-bromomethyl-1-iodobenzene (5)
Potassium acetate (2.52 g,
25.7 mmol) was added in small portions over 1 h to a stirred solution
of 1,3-bisbromo-methyl-5-iodobenzene 4 (10.0
g, 25.7 mmol) and TBAB (83.0 mg, 2.57 mmol) in anhyd DMF (200 mL).
The suspension was stirred at r.t. during 25 h. Ethyl acetate (600 mL)
was added to the mixture and the organic solution was washed with
H2O (3 × 200 mL), NH4Cl
sat. solution (200 mL) and brine (200 mL), then filtered (MgSO4)
and concentrated under vacuum. Purification by flash chromatography
(eluent: hexane-EtOAc, 90:10) afforded acetate 5 (3.92 g, 41%). R
f
= 0.50
(SiO2; hexane-EtOAc, 80:20). ¹H
NMR (400 MHz, CDCl3): δ = 7.70
(s, 1 H, ArH), 7.63 (s, 1 H, ArH), 7.33 (s, 1 H, ArH),
5.05 (s, 2 H, CH2O), 4.39 (s, 2 H, CH2Br),
2.13 (s, 3 H, CH3). ¹³C
NMR (100 MHz, CDCl3): δ = 170.6
(CO), 140.2 (ArC), 138.8 (ArC), 137.7 (ArCH),
137.0 (ArCH), 128.0 (ArCH),
94.3 (ArCI), 64.8 (CH2OAc),
31.5 (CH2Br), 21.0 (CH3). IR: νmax = 2932, 1737,
1570, 1357, 1377, 1236, 1057, 860 cm-¹.
MS(CI, NH3): m/z = 386,
388 [M + NH4]+.
HRMS(EI): m/z calcd for C10H10Br1I1O2 [M]+:
367.8903; found: 367.8907.
Data for biphenyl 9: R f = 0.30 (SiO2; hexane-EtOAc, 50:50). ¹H NMR (400 MHz, CDCl3): δ = 7.52 (s, 1 H, ArH), 7.39 (s, 1 H, ArH), 7.37 (s, 2 H, ArH), 7.30 (s, 1 H, ArH), 7.17 (s, 1 H, ArH), 5.00 (br s, 2 H, NH), 4.76 (s, 2 H, CH 2OH), 4.39 (s, 2 H, CH2N3), 4.34 [d, ³ J(H,H) = 5.0 Hz, 4 H, CH 2NH], 1.46 (s, 18 H, CH3C). ¹³C NMR (100 MHz, CDCl3): δ = 153.6 (CO), 140.0 (ArC), 138.6 (ArC), 138.4 (ArC), 137.3 (ArC), 133.4 (ArC), 123.0 (ArCH), 122.9 (ArCH), 122.8 (ArCH), 122.7 (ArCH), 122.6 (ArCH), 77.3 [C(CH3)3], 61.7 (CH2OH), 52.0 (CH2N3), 41.8 (CH2NHBoc), 25.8 (CH3). IR: νmax = 3406, 3335, 2978, 2932, 2096, 1684, 1513, 1247, 1160, 852 cm-¹. MS(ES+): m/z = 516 [M + NH4]+, 521 [M + Na]+. MS (ES-): m/z = 497 [M - H+]-. HRMS(ES+): m/z calcd for C26H39N6O5 [M + NH4]+: 515.2976; found: 515.2971.
9Data for receptor 3: R
f
= 0.50
(SiO2; toluene-EtOAc-EtOH, 50:50:5). ¹H
NMR [400 MHz, CDCl3-CD3OD
(92:8)]: δ = 8.60 (s,
2 H, spacer-ArH), 8.43 (s, 2 H, spacer-ArH), 8.29 (s, 2 H, spacer-ArH), 8.27 (s, 2 H, spacer-ArH), 8.22 [t, ³
J(H,H) = 4.8
Hz, 2 H, NH], 8.19 (s, 1 H, spacer-ArH),
8.11 (s, 1 H, spacer-ArH), 8.07 [t, ³
J(H,H) = 4.8
Hz, 2 H, NH], 7.93 (s, 1 H, spacer-ArH),
7.91 (s, 1 H, spacer ArH), 7.83 [t, ³
J(H,H) = 4.6
Hz, 2 H, NH], 7.69 (s, 2 H, ArH),
7.67 (s, 2 H, ArH), 7.62 (s, 2 H, ArH), 7.61 (s, 2 H, ArH),
7.52-7.05 (m, 64 H, ArH), 6.85
(s, 1 H, NHC), 6.82 (s, 1 H, NHC), 6.79 (s, 1 H, NHC), 6.77 (s,
1 H, NHC), 5.46 [A part of AB system, ²
J(H,H) = 11.7
Hz, 2 H, CH
2OCOAr],
5.05 [(B part of AB system, ²
J(H,H) = 11.7
Hz, 2 H, CH
2OCOAr],
4.73 [A part of AB system, ²
J(H,H) = 13.7
Hz, 2 H, CH
2NHCOAr], 4.50-4.45
(m, 32 H, BnCH
2, CH
2NHCOAr), 4.34 [B
part of AB system, ²
J(H,H) = 13.7
Hz, 2 H, CH
2NHCOAr],
3.90 (s, 6 H, CCH
2OBn), 3.88
(s, 18 H, CCH
2OBn). ¹³C
NMR (100 MHz, CDCl3): δ = 166.8,
166.7, 166.6, 166.0, 165.6, 165.3 (CO), 139.4, 139.3, 139.2, 139.0,
138.1 (ArC), 138.0 (BnArC),
136.7, 136.6, 136.5, 136.3, 136.2, 135.2, 135.1, 134.4 (ArC), 133.0, 131.7 (ArCH),
131.0 (ArC), 129.8, 129.7, 129.6, 129.0,
128.8 (ArCH), 128.4 (BnArCH), 128.1, 128.0 (ArCH),
127.7 (BnArCH), 127.4, 126.8, 126.5,
126.4, 126.1 (ArCH), 75.5 (BnCH2), 68.8, 68.7 (CCH2OBn), 68.1 (CH2OCOAr), 60.9, 60.8, 60.7,
60.6 (CCH2OBn), 44.8 (CH2NHCOAr). IR: νmax = 3306,
3029, 2862, 1721, 1659, 1515, 1452, 1255, 1091, 1075733 cm-¹.
MS (MALDI+):
m/z = 2772 [M + K]+.
The analysis programme was implemented as an Excel spreadsheet.
11In contrast, the single-step [2+2] cyclisation which forms the other end of the cage, and which is used twice in the synthesis of 1, is limited to spacers that cannot perform [1+1] cyclisations with the diaminobiphenyl units. The rigid isophthaloyl groups fulfil this criterion but many other potential spacers do not.