7. DESARROLLO
7.3 ANÁLISIS DE RESULTADOS DE ACUERDO A LA GENERACIÓN DE
The compounds were tested in a vial with a rubber lined screw cap. started with 20 mg/mL concentration (2mg in 0.1mL). The mixture of Solvent and compound was heated and sonicated. The solution was allowed to cool for 15-20 minutes. If a stable gel formed, 0.1 mL of the same solvent was added and the heating/sonication and cooling was repeated. The process was repeated until the gelation concentration and the concentration prior to the unstable gel was recorded as the Minimum Gelation Concentration (MGC).45
Synthesis of compound 28
The crude product was purified by flash chromatography by Hexane: EtOAc with 76% yield. 1H
NMR (400 MHz, CDCl3) δ 4.76 (d, J = 4.0, 1H), 3.87 (dd, J = 10.5, 5.2, 1H), 3.82 – 3.70 (m,
2H), 3.67 – 3.49 (m, 3H), 3.48 – 3.39 (m, 3H), 2.65 (s, 1H), 2.23 (d, J = 9.7, 1H), 1.50 (d, J =
10.9, 3H), 1.42 (d, J = 12.4, 3H).13C NMR (100 MHz, CDCl3) δ 101.9, 99.7, 80.8, 72.8, 71.7,
68.9, 62.3, 55.5, 23.4.
Synthesis of benzyl ester 30a
The crude product was purified by flash chromatography using Hexane: EtOAc with 30% yield. 1H NMR (400 MHz, CDCl
3) δ 8.17 (d, J = 7.5, 9H), 7.97 (d, J = 7.4, 3H), 7.68 (t, J = 7.5, 5H), 7.58 – 7.42 (m, 12H), 7.37 (t, J = 7.1, 4H), 5.95 – 5.80 (m, 2H), 5.24 – 5.07 (m, 3H), 3.91 (ddd, J
= 21.2, 16.2, 8.6, 5H), 3.40 (s, 3H), 1.44 (d, J = 45.5, 7H). 13C NMR (100 MHz, CDCl3) δ 169.9,
29
Synthesis of 2-benzyl ester 30b
The crude product was purified by flash chromatography using Hexane: EtOAc with 30% yield. 1H NMR (400 MHz, CDCl
3) δ 8.17 – 8.03 (m, 2H), 7.59 (t, J = 7.4, 1H), 7.52 – 7.41 (m, 2H), 5.01 (dt, J = 9.5, 3.8, 3H), 4.20 (t, J = 8.9, 1H), 3.91 (dd, J = 10.2, 4.7, 1H), 3.84 – 3.63 (m, 4H),
3.37 (s, 3H), 2.35 (s, 1H), 1.54 (s, 16H), 1.46 (s, 4H). 13C NMR (CDCl3, 100MHz) δ 174.9,
133.4, 129.9, 127.9, 103.8, 101.1, 76.3, 71.1, 69.0, 62.5, 55.5, 26.5.
Synthesis of napthoyl dimer compound 31a
The pure product was purified by flash chromatography using Hexane: EtOAc with 26% yield. 1H NMR (400 MHz, CDCl
3) δ 8.92 (t, J = 13.6, 1H), 8.73 – 8.63 (m, 1H), 8.39 – 8.24 (m, 1H), 8.08 – 7.76 (m, 6H), 7.67 – 7.30 (m, 8H), 6.05 (t, J = 9.6, 1H), 5.34 (dt, J = 13.6, 6.8, 1H), 4.95
(d, J = 7.4, 1H), 4.37 – 4.16 (m, 2H), 4.12 – 3.79 (m, 4H), 3.47 (s, 3H), 1.71 – 1.37 (m, 5H).
Synthesis of napthoyl 2-ester compound 31b
The pure product was purified by flash chromatography using Hexane: EtOAc with a yield of 36%. 1H NMR (400 MHz, CDCl3) δ 8.90 (d, J = 8.3, 1H), 8.68 (d, J = 9.1, 1H), 8.29 (d, J = 7.3,
1H), 7.91 (tdd, J = 18.3, 15.0, 7.9, 5H), 7.58 – 7.33 (m, 7H), 6.05 (t, J = 9.5, 1H), 5.35 (dd, J =
10.0, 3.7, 1H), 5.23 (d, J = 3.7, 1H), 4.34 – 4.14 (m, 2H), 4.09 – 3.79 (m, 4H), 3.43 (d, J = 25.9,
30
Synthesis of heptanoyl dimer compound 32a
The pure product was purified by flash chromatography using Hexane:EtOAc with a yield of 22%. 1H NMR (400 MHz, CDCl3) δ 4.92 (d, J = 3.7, 1H), 4.75 (dd, J = 9.7, 3.8, 1H), 4.02 (td, J
= 9.3, 2.8, 1H), 3.88 (dd, J = 10.5, 5.0, 1H), 3.77 (t, J = 10.3, 1H), 3.72 – 3.55 (m, 2H), 3.36 (s,
3H), 2.40 (t, J = 7.5, 2H), 2.27 (d, J = 2.8, 1H), 1.73 – 1.60 (m, 1H), 1.58 – 1.22 (m, 21H). ) 13C
NMR (100 MHz, CDCl3) δ 173.8, 101.1, 99.4, 81.9, 72.3, 68.3, 64.5, 63.5, 53.9, 36.6, 30.9, 28.9,
25.6, 21.7, 14.6.
Synthesis of heptanoyl 2-ester compound 32b
The pure product was purified by flash chromatography using Hexane:EtOAc, product yield was 15%. 1H NMR (400 MHz, CDCl3) δ 5.42 (t, J = 9.5, 1H), 4.96 – 4.81 (m, 1H), 4.75 (dd, J = 9.7, 3.8, 1H), 4.02 (td, J = 9.3, 2.8, 1H), 3.88 (dd, J = 10.4, 5.0, 1H), 3.83 – 3.70 (m, 1H), 3.70 – 3.54 (m, 2H), 3.37 (d, J = 3.2, 3H), 2.44 – 2.36 (m, 2H), 1.72 – 1.58 (m, 2H), 1.58 – 0.81 (m, 24H) 13C NMR (100 MHz, CDCl 3) δ 174.9, 102.1, 99.0, 82.3, 71.0, 69.0, 65.5, 62.5, 54.2, 36.9, 31.7, 29.0, 25.8, 22.7, 14.2
Synthesis of benzylidene benzyl amine compound 35
The compound was purified by flash chromatography using Hexane:DCM: MeOH, the pure product was obtained in 91% yield. 1H NMR (400 MHz, DMSO) δ 7.73 (t, J = 11.0, 1H), 7.43 (d,
J = 4.8, 3H), 7.39 – 7.33 (m, 5H), 7.33 – 7.15 (m, 11H), 5.59 (d, J = 10.6, 1H), 5.25 (t, J = 8.0,
1H), 4.64 (t, J = 6.3, 1H), 4.16 (dt, J = 11.4, 5.8, 1H), 3.87 (td, J = 9.8, 3.6, 1H), 3.78 – 3.47 (m,
31
171.9, 140.7, 138.4, 129.6, 128.9, 128.8, 101.6, 99.4, 82.4, 68.7, 68.7, 63.3, 55.3, 53.9, 52.5, 52.0, 40.6, 40.4
Synthesis of pyridinium acetamide compound 36
The compound was purified by flash chromatography using Hexane:DCM: MeOH, the pure product was obtained in 89% yield. 1H NMR (CDCl3, 400MHz) δ (ppm) 8.83(dd, J = 1.5, 5.5
Hz, 2H), 8.49 (td, J = 1.5, 8.1 Hz, 1H), 8.02 (dd, J = 6.6, 7.7 Hz, 2H),7.45-7.41 (m, 2H), 7.30-
7.25 (m, 3H), 5.56 (s, 1H), 4.71 (m, 1H), 4.23-4.18 (m, 1H), 4.09 (dd, J = 3.7, 10.3 Hz, 1H), 3.92
(pt, J = 9.5, 9.9 Hz, 1H), 3.82-3.72 (m, 3H), 3.62 (t, J =9.2 Hz, 1H), 3.43 (s, 3H). 13C NMR
(CDCl3, 100MHz) δ 166.4, 147.8, 146.8, 138.0, 129.8, 128.7, 128.7, 128.4, 128.1, 126.8, 103.3, 100.4, 81.9, 70.6, 69.2, 64.3, 56.3
Synthesis of imidazole derivative with isopropylidene head group 37
The compound was purified by flash chromatography using Hexane:DCM:MeOH, the pure product was obtained in 89% yield. 1H NMR (400 MHz, DMSO) δ 8.30 (t, J = 14.5, 1H), 7.60 (s,
1H), 7.40 (dd, J = 29.7, 4.3, 6H), 6.82 (d, J = 41.6, 1H), 4.69 (s, 2H), 4.63 (d, J = 3.4, 1H), 4.16
(dd, J = 9.9, 4.6, 1H), 3.83 (dt, J = 27.3, 9.7, 2H), 3.77 (s, 6H), 3.32 (d, J = 18.0, 21H), 3.06 (dd, J = 14.5, 7.2, 2H), 2.48 (s, 7H). ). 13C NMR (100MHz, DMSO) δ 170.1, 140.3, 130.5, 128.7,
128.5, 127.4, 103.0, 100.1, 82.7, 70.1, 69.7, 63.8, 37.9
Synthesis of Head group compound 40
The crude product was purified by flash chromatography using Hexane:DCM:MeOH. The pure potion of the compound isolated was 84%. 1H NMR (400 MHz, CDCl3) δ 5.27 (d, J = 24.2, 1H),
32
4.64 (d, J = 3.6, 1H), 3.86 (dd, J = 10.5, 5.2, 1H), 3.75 (t, J = 10.4, 1H), 3.67 – 3.47 (m, 4H),
3.42 – 3.34 (m, 4H), 2.74 (dd, J = 9.3, 3.7, 1H), 1.60 – 1.39 (m, 10H). 13C NMR (100 MHz,
CDCl3) δ 173.2, 102.1, 101.5, 82.2, 72.1, 69.3, 62.8, 56.9, 55.7, 26.4, 23.3
Synthesis of Head group compound 41
Crude product was purified by flash chromatography using Hexane:DCM;MeOH. The pure product was obtained with the yield of 71%. 1H NMR (400 MHz, CDCl3) δ 4.64 (d, J = 3.7, 1H),
3.85 (dt, J = 8.0, 4.0, 1H), 3.78 (s, 2H), 3.75 (s, 1H), 3.73 (s, 1H), 3.67 – 3.45 (m, 4H), 3.40 –
3.33 (m, 4H), 2.73 (dt, J = 9.2, 4.6, 1H), 1.43 (dd, J = 34.8, 19.2, 10H). 13C NMR (100 MHz,
CDCl3) δ 100.1, 98.8, 74.8, 70.9, 63.1, 62.4, 56.9, 54.9, 29.2
Synthesis of isopropylidine head group compound 42
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, pure portion of isolated product was 87%. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.6, 2H), 6.88
(d, J = 8.7, 2H), 5.49 (s, 1H), 4.67 (d, J = 3.6, 1H), 4.25 (dd, J = 9.5, 4.2, 1H), 3.83 – 3.66 (m,
7H), 3.49 – 3.36 (m, 4H), 2.77 (dd, J = 9.6, 3.6, 1H).13C NMR (100 MHz, CDCl3) δ 172.8, 102.1,
101.5, 82.2, 72.1, 69.3, 62.8, 56.9, 55.6, 55.5, 20.5
Synthesis of isopropropylidine imidazole derivative 43
The compound was purified by flash chromatography using Hexane:DCM:MeOH, pure portion of isolated product yield was 91%. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 9.1, 1H), 7.66 –
7.30 (m, 7H), 5.27 (d, J = 12.6, 1H), 4.67 (d, J = 3.8, 1H), 4.12 (td, J = 9.5, 3.8, 1H), 3.89 – 3.85
33
(s, 1H), 1.47 (d, J = 10.8, 4H), 1.45 (s, 4H). 13C NMR (100 MHz, CDCl3) δ 173.1, 139.6, 128.8,
124.6, 100.0, 99.2, 80.9, 74.4, 63.5, 62.5, 55.4, 45.5, 55.2, 19.3
Synthesis of benzyl amine derivative of isopropylidene head group compound 44
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained as a white powder in 86% yield. 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J =
9.1, 1H), 7.37 – 7.20 (m, 7H), 5.26 (d, J = 12.6, 1H), 4.63 (d, J = 3.8, 1H), 4.12 (td, J = 9.5, 3.8,
1H), 3.88 – 3.82 (m, 1H), 3.74 (td, J = 12.9, 5.1, 5H), 3.65 – 3.57 (m, 2H), 3.46 – 3.30 (m, 5H),
3.27 (s, 1H), 3.23 (s, 1H), 1.49 (d, J = 10.8, 4H), 1.45 (s, 4H). 13C NMR (100 MHz, CDCl3) δ
173.1, 155.4, 139.5, 128.8, 128.4, 127.6, 100.1, 99.2, 74.9, 71.1, 63.5, 62.5, 55.4, 53.5, 51.9, 29.3, 19.3
Synthesis of pyridine derivative of isopropylidene head group compound 45
The crude of the product was dried and product was obtained as a white powder with the yield of 91%. 1H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 6.3, 2H), 8.42 (t, J = 7.3, 1H), 7.96 (t, J = 6.8, 3H), 5.67 (d, J = 15.8, 1H), 5.52 (d, J = 15.8, 1H), 4.61 (d, J = 3.5, 1H), 3.97 (dd, J = 10.0, 3.6, 1H), 3.73 (ddd, J = 26.5, 13.4, 7.1, 5H), 3.63 – 3.38 (m, 17H), 3.37 – 3.21 (m, 8H), 1.43 (s, 5H), 1.31 (d, J = 28.4, 5H). 13C NMR (100 MHz, CDCl3) δ 164.6, 146.4, 145.9, 127.8, 100.1, 98.9, 74.3, 69.5, 63.6, 62.4, 62.3, 55.9, 55.5, 55.2, 29.0, 19.0 Synthesis of compound 47
About 10 gm of p-anisaldehyde was dissolved in 30mL of methanol in 250 mL of round bottom flask (RBF). 1.2 equivalents of triethyl orthoformate were added into the reaction flask. Catalytic
34
amount of PTSA was added into RBF. Reflux the reaction at 75o C for 8 hrs. Neutralize the
reaction with 2 equivalents of sodium methoxide and filtered it. Resulting liquid was concentrated and dried it. Product was yellowish color liquid with 89% yield.
Synthesis of head group 49
5.00g of N-Acetyl-D-glucosamine was dissolved in 50 mL of methanol. The reaction mixture
was refluxed with Amberlite IR-120 resin (5.00 g) over night. Resin was filtered by methanol, which was removed by drying in high vacuum pump to yield 4.9 g (90%) α and β mixtures of anomers (~8:1). α/β mixtures of methyl group at the anomeric position was dissolved in 25mL of DMF, 9.5 mL of p-methoxy dimethyl benzylidene acetal, and 0.3g of p-toluenesulfonic acid at 60°C for 2hrs. DMF was removed in vacuum to yield a 5.5g (84%) white solid (mixture of α and β anomers). The α anomer was purified by column, which was then dissolved in 75 mL of refluxing 3N KOH ethanol for 18 hours. Reaction was diluted with a 2% MeOH in DCM (~150 mL) and water (2x100 mL). After drying the DCM layer over anhydrous sodium sulphate, crude was purified by column chromatography using 2% MeOH in DCM product yield was 71%.
General procedure for the synthesis of amide
To a 50 mL of round bottom flask 50 mg of head group was dissolved in 2 mL of THF or DCM and 2 equivalent of potassium carbonate or pyridine was added into the reaction flask. Cooled the reaction mixture at 00 C and 1 equivalent of the corresponding acid chloride were added drop
wise to the solution. The mixture was left stirring for 6-10 hrs, after which the mixture was concentrated under nitrogen. The crude residue was purified by flash chromatography using hexane/DCM/MeOH. The resulting purified compound was tested for their gelation activity.
35
Synthesis of hexyl amide compound 50
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained in 87% yield. 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.7, 2H), 6.85 (d,
J = 8.8, 2H), 5.83 (d, J = 8.5, 1H), 5.49 (s, 1H), 4.69 (d, J = 3.8, 1H), 4.26 – 4.16 (m, 2H), 3.86
(td, J = 9.6, 3.2, 1H), 3.77 (d, J = 1.1, 4H), 3.76 – 3.71 (m, 2H), 3.57 – 3.51 (m, 1H), 3.37 (t, J =
5.3, 4H), 3.13 (d, J = 3.3, 1H), 2.22 (t, J = 7.7, 2H), 1.68 – 1.58 (m, 3H), 1.35 – 1.22 (m, 5H),
0.87 (dd, J = 7.0, 6.0, 4H). 13C NMR (100 MHz, CDCl3) δ 174.9, 160.4, 129.9, 127.9, 113.8,
102.1, 82.3, 71.1, 69.0, 62.5, 55.5, 55.4, 54.2, 36.8, 31.5, 25.5, 22.6
Synthesis of heptyl amide compound 51
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained in 88% yield. 1H NMR (400 MHz, CDCl3) δ 7.45 – 7.39 (m, 2H), 6.91 –
6.85 (m, 2H), 5.82 (d, J = 8.7, 1H), 5.53 (s, 1H), 4.71 (d, J = 3.9, 1H), 4.29 – 4.19 (m, 2H), 3.89
(td, J = 9.6, 3.2, 1H), 3.82 – 3.74 (m, 6H), 3.61 – 3.54 (m, 1H), 3.43 – 3.37 (m, 4H), 3.06 (d, J =
3.3, 1H), 2.29 – 2.22 (m, 2H), 1.64 (dd, J = 15.2, 7.6, 2H), 1.32 (dd, J = 15.7, 5.7, 8H), 0.88 (t, J
= 6.9, 4H).13C NMR (100 MHz, CDCl3) δ 174.9, 160.4, 129.9, 127.9, 115.6, 113.8, 102.1, 99.0,
82.3, 71.0, 69.0, 62.6, 55.5, 54.2, 36.9, 31.7, 29.0, 25.7, 22.7, 14.2
Synthesis of octyl amide compound 52
The crude product was purified by flash chromatography using Hexane: DCM, the pure product was obtained in 82% yield. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.6, 2H), 6.84 (t, J = 12.3,
36
(dd, J = 19.4, 9.6, 1H), 3.81 (s, 4H), 3.76 – 3.68 (m, 2H), 3.61 – 3.48 (m, 1H), 3.36 (d, J = 15.9,
4H), 2.31 – 2.14 (m, 2H), 1.71 – 1.54 (m, 2H), 1.38 – 1.15 (m, 9H), 0.96 – 0.79 (m, 3H). 13C
NMR (100 MHz, CDCl3) δ 172.5, 158.0, 127.5, 125.5, 111.4, 99.7, 96.6, 79.8, 68.4, 66.6, 60.2,
53.1, 51.8, 34.4, 29.5, 27.8, 26.9, 26.8, 21.2, 11.9
Synthesis of benzyl amide compound 53
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained in 87% yield. 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.6, 2H), 7.52 (t,
J = 7.4, 1H), 7.43 (dd, J = 12.4, 5.5, 4H), 7.26 (s, 1H), 6.88 (d, J = 8.8, 2H), 6.53 (d, J = 8.6, 1H),
5.53 (s, 1H), 4.83 (d, J = 3.8, 1H), 4.47 – 4.40 (m, 1H), 4.28 (dd, J = 9.0, 3.6, 1H), 4.01 (td, J =
9.7, 3.2, 1H), 3.86 – 3.74 (m, 6H), 3.62 (t, J = 9.0, 1H), 3.43 (s, 3H), 3.19 (d, J = 3.3, 1H) 13C
NMR (100 MHz, CDCl3) δ 168.7, 160.5, 132.2, 129.7, 128.9, 127.9, 127.4, 113.9, 102.1, 99.1,
82.2, 70.9, 69.0, 62.6, 55.6, 55.5, 54.7
Synthesis of 5-hexynoyl amide compound 55
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained in 87% yield. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.4, 2H), 6.88 (d,
J = 8.5, 2H), 5.90 (d, J = 8.7, 1H), 5.52 (s, 1H), 4.71 (d, J = 3.7, 1H), 4.30 – 4.19 (m, 2H), 3.89
(td, J = 9.5, 2.8, 1H), 3.83 – 3.71 (m, 6H), 3.56 (t, J = 9.0, 1H), 3.38 (d, J = 23.2, 4H), 2.99 (d, J
= 3.1, 1H), 2.40 (t, J = 7.3, 2H), 2.28 (dd, J = 8.0, 5.1, 2H), 1.99 (s, 1H), 1.88 (dt, J = 13.2, 6.7,
2H).13C NMR (100 MHz, CDCl3) δ 173.8, 160.5, 129.8, 127.9, 113.9, 102.1, 99.0, 82.2, 75.8,
37
Synthesis of pyridine amide 57
The crude product was purified by flash chromatography using Hexane: DCM: MeOH , the pure product was obtained in 90% yield. 1H NMR (400 MHz, CDCl3) δ 8.80 (d, J = 5.8, 2H), 8.33 (dd,
J = 15.2, 8.0, 2H), 7.88 (t, J = 7.0, 2H), 7.27 (d, J = 4.8, 1H), 6.72 (d, J = 8.6, 2H), 5.53 (d, J =
15.9, 1H), 5.41 (d, J = 15.9, 1H), 5.37 (s, 1H), 4.58 (d, J = 3.4, 1H), 4.10 (dd, J = 9.9, 4.5, 1H),
4.00 – 3.82 (m, 13H), 3.75 – 3.56 (m, 7H), 3.42 (t, J = 9.2, 1H), 3.29 (s, 4H), 3.20 (s, 1H).13C
NMR (100 MHz, CDCl3) δ 164.6, 160.3, 146.3, 145.9, 129.8, 127.8, 127.7, 115.6, 113.6, 101.9,
98.6, 98.4, 81.7, 68.9, 62.7, 62.4, 55.4, 55.3, 55.0
Synthesis of benzyl amide derivative 58
The crude product was purified by flash chromatography using Hexane: DCM: MeOH, the pure product was obtained in 87% yield. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 9.1, 1H), 7.42 (d,
J = 8.7, 2H), 7.37 – 7.24 (m, 6H), 6.87 (d, J = 8.6, 2H), 5.51 (s, 1H), 4.68 (d, J = 3.8, 1H), 4.26
(dd, J = 9.2, 3.8, 1H), 4.18 (td, J = 9.6, 3.8, 1H), 3.90 (t, J = 9.6, 1H), 3.84 – 3.75 (m, 5H), 3.75 –
3.68 (m, 3H), 3.56 (t, J = 9.0, 1H), 3.43 – 3.35 (m, 4H), 3.29 (s, 1H), 3.24 (d, J = 3.7, 1H). 13C
NMR (100 MHz, CDCl3) δ 173.2, 160.4, 139.5, 129.9, 128.8, 128.4, 127.9, 127.7, 113.9, 102.1,
38