Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides

Article abstract of DOI:10.1021/ja100579z

Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6-31G. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed.

Full text of DOI:10.1021/ja100579z

Synthesis, Structural Investigations, Hydrogen-Deuterium Exchange
Studies and Molecular Modeling of Conformationally Stablilized
Aromatic Oligoamides
Yan Yan,† Bo Qin,† Changliang Ren,† Xiuying Chen,‡ Yeow Kwan Yip,† Ruijuan Ye,†
Dawei Zhang,§ Haibin Su,‡ and Huaqiang Zeng*,†
Department of Chemistry and MedChem Programme, National University of Singapore, 3 Science
Drive 3, Singapore, 117543, Department of Materials Science, Nanyang Technological University,50
Nanyang Avenue, Singapore, 639798, Department of Chemistry & Biological Chemistry, Nanyang
Technological University, 21 Nanyang Link, Singapore, 637371
Email: chmzh@nus.edu.sg
Supporting Information
Table of Content
1. Synthetic Procedures/Characterizations................................................................. S2
2. Amide Hydrogen-Deuterium Exchange Experiments ......................................... S17
3. Ab initio Calculation................................................................................................ S19
4. Determination of Crystal Structures..................................................................... S19
5. Crystal Data and Structure Refinement ............................................................... S20
S1

Synthetic Procedures/Characterizations
All the reagents were obtained from commercial suppliers and used as received unless otherwise noted.
Aqueous solutions were prepared from distilled water. The organic solutions from all liquid extractions were
dried over anhydrous Na2SO4 for a minimum of 15 minutes before filtration. Reactions were monitored by
thin-layer chromatography (TLC) on silica gel pre-coated glass plate (0.225 mm thickness, 60F-254, E.
Merck). Flash column chromatography was performed using pre-coated 0.2 mm silica plates from Selecto
Scientific. Chemical yields refer to pure isolated substances. 1H and 13C NMR spectra were recorded on either
a Bruker ACF-300 or AVF-500 spectrometer. In addition, key compounds were characterized by 2D NOSEY
1
and/or X-ray Diffraction. H NMR spectra were recorded on Bruker ACF300 (300 MHz) and ACF500
spectrometers (500 MHz). The solvent signal of CDCl3 was referenced at δ = 7.26, and DMSO-d6 at 2.50.
1
Coupling constants (J values) are reported in Hertz (Hz). H NMR data are recorded in the order: chemical
shift value, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad), number of protons
that gave rise to the signal and coupling constant, where applicable. 13C Spectra are proton-decoupled and
recorded on Bruker ACF300 (300 MHz) and ACF500 spectrometers (500 MHz). The solvent, CDCl3 was
referenced at δ = 77 ppm and DMS0-d6 at 39.5 ppm. CDCl3 (99.8% deuterated) was purchased from Aldrich
and used without further purification.
Compound 1a: 2,5-dihydroxybenzoic acid (4.62 g, 30.0 mmol) was dissolved in MeOH (60 mL), to which
concentrated H2SO4 (5 mL) was added. The mixture was heated under reflux for 48 hrs. The solvent was then
removed in vacuo and the residue was dissolved in CH2Cl2 (100 mL), washed with water (2 x 50 mL) and
dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the pure product 1a as a light brown solid. Yield:
4.89 g, 97%. 1H NMR (300 MHz, CDCl3) δ 10.33 (s, 1H), 7.28 (d, 1H, J = 3.1), 7.01 (d, 1H, J = 8.9), 6.88 (d,
1H, J = 8.9), 4.76 (s, 1H), 3.93 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 170.89, 156.12, 148.52, 124.85, 119.09,
115.55, 112.87, 53.08. HRMS-ESI: calculated for [M]+ (C8H8O4): m/z 167.0344 found: m/z 167.0343.
Compound 1b: 1a (1.34 g, 8.00 mmol) was dissolved in anhydrous acetone (30 mL), to which anhydrous
K2CO3 (2.00 g, 14.5 mmol) and iodomethane (0.50 mL, 8.00 mmol) was added. The mixture was heated
under reflux for 48 hrs. The reaction mixture was then filtered and the solvent was removed in vacuo. The
concentrate was dissolved in CH2Cl2 (100 mL), washed with water (2 x 50 mL) and dried over anhydrous
Na2SO4. Removal of CH2Cl2 gave the crude product, which was purified by flash column chromatography
(silica gel) using hexane/ethyl acetate (4:1 v/v) as the eluent to give pure product 1b as a yellow liquid. Yield:
0.95 g, 65%. 1H NMR (300 MHz, CDCl3) δ 10.33 (s, 1H), 7.07 (d, 1H, J = 3.2), 7.04 (d, 1H, J = 3.2), 6.90 (d,
1H, J = 5.9), 3.92 (s, 3H), 3.75 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 170.60, 156.41, 152.35, 124.21, 118.74,
112.12, 60.64, 55.94, 52.50. HRMS-ESI: calculated for [M]+ (C9H10O4): m/z 181.0579 found: m/z181.0579.
Compound 1c: 1a (1.34 g, 8.00 mmol) was dissolved in anhydrous acetone (30 mL), to which anhydrous
K2CO3 (2.00 g, 14.5 mmol) and 1-bromooctane (1.38 mL, 8.00 mmol) was added. The mixture was heated
under reflux for 48 hrs. The reaction mixture was then filtered and the solvent was removed in vacuo. The
concentrate was dissolved in CH2Cl2 (40 mL), washed with water (2 x 30 mL) and dried over anhydrous
Na2SO4. Removal of CH2Cl2 gave the crude product, which was recrystallized from MeOH to give pure
product 1c as a light yellow solid. Yield: 1.57 g, 70%. 1H NMR (300 MHz, CDCl3) δ 10.35 (s, 1H), 7.29 (d,
S2

1H, J = 3.1), 7.08 (d, 1H, J = 9.0), 6.90 (d, 1H, J = 9.0), 3.95 (s, 3H), 3.88 (m, 2H), 1.76 (m, 2H), 1.42 (m,
2H), 1.25 (m, 8H), 0.89 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 171.02, 156.63, 152.24, 125.25, 119.10,
113.57, 112.53, 69.51, 52.92, 32.49, 30.03, 29.97, 29.91, 26.71, 23.33, 14.76. HRMS-EI: calculated for [M]+
(C16H24O4): m/z 280.1675 found: m/z 280.1677.
Compound 1d: 1a (1.34 g, 8.00 mmol) was dissolved in anhydrous acetone (30 mL), to which anhydrous
K2CO3 (2.00 g, 14.5 mmol) and 2-bromopropane (3.80 mL, 8.00 mmol) was added. The mixture was heated
under reflux for 48 hrs. The reaction mixture was then filtered and the solvent was removed in vacuo. The
concentrate was dissolved in CH2Cl2 (40 mL), washed with water (2 x 50 mL) and dried over anhydrous
Na2SO4. Removal of CH2Cl2 gave the crude product, which was purified by flash column chromatography
(silica gel) using hexane/ethyl acetate (4:1 v/v) as the eluent to give pure product 1d as a yellow liquid. Yield:
0.86 g, 51%. 1H NMR (300 MHz, CDCl3) δ 10.33 (s, 1H), 7.28 (d, 1H, J = 3.1), 7.02 (d, 1H, J = 5.3), 6.86 (d,
1H, J = 5.3), 4.38 (m, 1H), 3.89 (s, 3H) 1.31 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 170.86, 156.66, 150.67,
126.71, 118.94, 116.18, 112.59, 71.82, 52.79, 22.51. HRMS-EI: calculated for [M]+ (C11H14O4): m/z 210.0892
found: m/z 210.0893.
Compound 1e: 1b (0.18 g, 1.00 mmol) and Montmorillonite K10 (0.50 g) were added to a suspension of
bismuth nitrate (0.39 g, 1.00 mmol) in THF (10 mL). The mixture was stirred at room temperature for 1 h and
solid was filtered. Solvent was then removed in vacuo and the residue was dissolved in CH2Cl2. The filtrate
was washed with 1M HCl (1 x 50 mL), water (2 x 50 mL) and dried over anhydrous Na2SO4. Removal of
CH2Cl2 gave the pure product 1e as a yellow solid. Yield: 0.14 g, 63%. 1H NMR (300 MHz, CDCl3) δ 11.46
(s, 1H), 7.72 (d, 1H, J = 7.9), 7.70 (d, 1H, J = 7.9), 4.01 (s, 3H), 3.84 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
169.28, 151.37, 150.51, 138.27, 122.42, 117.12, 68.61, 56.95, 53.82. HRMS-ESI: calculated for [M]-
(C9H9NO6): m/z 226.0352 found: m/z 226.0364.
Compound 1f: 1c (0.28 g, 1.00 mmol) and Montmorillonite K10 (0.50 g) were added to a suspension of
bismuth nitrate (0.39 g, 1.00 mmol) in THF (10 mL). The mixture was stirred at room temperature for 1 h and
solid was filtered. Solvent was then removed in vacuo and the residue was dissolved in CH2Cl2. The filtrate
was washed with 1M HCl (1 x 50 mL), water (2 x 50 mL) and dried over anhydrous Na2SO4. Removal of
CH2Cl2 gave the crude product, which was recrystallized from MeOH to give pure product 1f as a yellow
solid. Yield: 0.19 g, 58%. 1H NMR (300 MHz, CDCl3) δ 11.44 (s, 1H), 7.72 (d, 1H, J = 3.3), 7.69 (d, 1H, J =
3.1), 4.00 (s, 3H), 3.96 (m, 2H), 1.79 (m, 2H), 1.31 (m, 2H), 1.29 (m, 8H), 0.89 (m, 3H). 13C NMR (75 MHz,
CDCl3) δ 169.30, 150.90, 150.33, 138.19, 122.97, 117.68, 116.85, 69.95, 53.73, 32.40, 29.88, 29.81, 29.64,
26.52, 23.26, 14.68. HRMS-ESI: calculated for [M]+ (C16H23NO6): m/z 324.1447 found: m/z 324.1461.
Compound 1g: 1d (0.21 g, 1.00 mmol) and Montmorillonite K10 (0.50 g) were added to a suspension of
bismuth nitrate (0.39 g, 1.00 mmol) in THF (10 mL). The mixture was stirred at room temperature for 1 h and
solid was filtered. Solvent was then removed in vacuo and the residue was dissolved in CH2Cl2. The filtrate
was washed with 1M HCl (1 x 50 mL), water (2 x 50 mL) and dried over anhydrous Na2SO4. Removal of
CH2Cl2 gave the pure product 1g as a yellow liqid. Yield: 0.17 g, 67%. 1H NMR (300 MHz, CDCl3) δ 11.44
(s, 1H), 7.68 (d, 1H, J = 3.1), 7.66 (d, 1H, J = 3.1), 4.49 (m, 1H), 3.97 (s, 3H), 1.41 (s, 6H). 13C NMR (75
S3

MHz, CDCl3) δ 169.24, 150.35, 149.50, 124.63, 122.31, 119.37, 118.16, 72.43, 53.67, 22.42. HRMS-ESI:
calculated for [M]+ (C11H13NO6): m/z 254.0665 found: m/z 255.0660.
Compound 1h: 1e (2.27 g, 10.0 mmol) was dissolved in anhydrous DMF (30 mL), to which anhydrous
K2CO3 (4.00 g, 25.0 mmol) and iodomethane (0.75 mL, 12.0 mmol) was added. The mixture was heated
0
under reflux for 60 C hrs. CH2Cl2 (100 mL) was then added and the reaction mixture was filtered. The
solvent was removed in vacuo and the concentrate was dissolved in CH2Cl2 (100 mL), washed with water (2
x 50 mL) and dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the pure product 1h as a red solid.
Yield: 2.19 g, 91%. 1H NMR (300 MHz, CDCl3) δ 7.54 (s, 1H), 7.42 (s, 1H), 3.94 (s, 6H), 3.86 (s, 3H). 13
C
NMR (75 MHz, CDCl3) δ 165.38, 155.41, 147.39, 146.37, 128.78, 121.66, 114.21, 65.01, 56.90, 53.48.
HRMS-EI: calculated for [M]+ (C10H11NO6): m/z 241.0586 found: m/z 241.0587.
Compound 1i: 1f (3.25 g, 10.0 mmol) was dissolved in anhydrous DMF (30 mL), to which anhydrous
K2CO3 (4.00 g, 25.0 mmol) and iodomethane (0.75 mL, 12.0 mmol) was added. The mixture was heated
0
under 60 C for 4 hrs. CH2Cl2 (100 mL) was then added and the reaction mixture was filtered. The solvent
was removed in vacuo and the concentrate was dissolved in CH2Cl2 (100 mL), washed with water (3 x 50
mL) and dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the crude product, which was recrystallized
from MeOH to give pure product 1i as a yellow solid. Yield: 2.44 g, 72%. 1H NMR (300 MHz, CDCl3) δ 7.52
(d, 1H, J = 3.3), 7.40 (d, 1H, J = 3.1), 3.93 (m, 2H), 3.92 (s, 3H), 3.61 (s, 3H), 1.77 (m, 2H), 1.43 (m, 2H),
1.27 (m, 8H), 0.86 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 166.09, 150.52, 149.97, 134.44, 121.35, 115.16,
114.63, 68.91, 54.81, 51.57, 31.81, 29.64, 29.37, 28.95, 25.96, 22.83, 14.06. HRMS-ESI: calculated for [M]+
(C17H25NO6): m/z 339.1682 found: m/z 339.1691.
Compound 1j: 1g (2.55 g, 10.0 mmol) was dissolved in anhydrous DMF (30 mL), to which anhydrous
K2CO3 (4.00 g, 25.0 mmol) and iodomethane (0.75 mL, 12.0 mmol) was added. The mixture was heated
0
under 60 C for 4 hrs. CH2Cl2 (100 mL) was then added and the reaction mixture was filtered. The solvent
was removed in vacuo and the concentrate was dissolved in CH2Cl2 (100 mL), washed with water (2 x 50
mL) and dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the pure product 1j as a red liquid. Yield:
1
2.19 g, 81%. H NMR (300 MHz, CDCl3) δ 7.52 (d, 1H, J = 3.2), 7.39 (d, 1H, J = 3.2), ,4.55 (m, 1H), 3.94 (s,
6H), 1.36 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 165.48, 153.81, 147.12, 146.40, 128.72, 123.45, 115.93,
72.20, 65.01, 53.47, 22.82. HRMS-EI: calculated for [M]+ (C12H15NO6): m/z 269.0899 found: m/z 269.0902.
Compound 1k: 1h (1.25 g, 5.20 mmol) was dissolved in hot MeOH (20 mL), to which 1N NaOH (10 mL,
10.0 mmol) was added. The mixture was heated under reflux for 1 h and then more water (50 mL) was added.
The aqueous layer was neutralized by addition of 1M HCl (15 mL). The precipitated crude product was
collected by filtration, which was recrystallized from MeOH to give a yellow solid 1k. Yield: 0.63 g, 53%. 1H
NMR (300 MHz, CDCl3) δ 13.61 (s, 1H), 7.66 (d, 1H, J = 3.3), 7.51 (d, 1H, J = 3.3), 3.84 (s, 3H), 3.82 (s,
3H). 13C NMR (125 MHz, DMSO-d6) δ 165.32, 154.47, 145.58, 144.57, 129.01, 120.05, 112.45, 63.81, 56.33.
HRMS-ESI: calculated for [M]+ (C9H9NO6): m/z 226.0352 found: m/z 226.0346.
Compound 1l: 1i (2.80 g, 8.30 mmol) was dissolved in hot MeOH (30 mL), to which 1N NaOH (17 mL,
17.0 mmol) was added. The mixture was heated under reflux for 1 h and then quenched with water (100 mL).
S4

The aqueous layer was neutralized by addition of 1M HCl (25 mL). The precipitated crude product was
collected by filtration, which was recrystallized from MeOH to give a yellow solid 1l. Yield: 2.30 g, 85%. 1H
NMR (300 MHz, CDCl3) δ 13.67 (s, 1H), 7.65 (d, 1H, J = 3.2), 7.53 (d, 1H, J = 3.1), 3.92 (m, 2H), 3.59 (s,
3H), 1.70 (m, 2H), 1.40 (m, 2H), 1.19 (m, 8H), 0.79 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 165.44, 154.92,
146.40, 144.78, 125.81, 122.18, 116.07, 69.41, 64.78, 31.76, 29.21, 29.16, 28.89, 25.85, 22.62, 14.06.
HRMS-EI: calculated for [M]+ (C16H23NO6): m/z 324.1447 found: m/z 324.1453.
Compound 1m: 1j (2.69 g, 10.0 mmol) was dissolved in hot MeOH (40 mL), to which 1N NaOH (20 mL,
20.0 mmol) was added. The mixture was heated under reflux for 1h and then more water (100 mL) was added.
The aqueous layer was neutralized by addition of 1M HCl (30 mL). The precipitated crude product was
collected by filtration, which was recrystallized from MeOH to give a yellow solid 1m. Yield: 1.68 g, 66%.
1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J = 3.2), 7.54 (d, 1H, J = 3.2), 4.60 (m, 1H), 4.02 (s, 3H), 1.38 (s,
6H). 13C NMR (125 MHz, DMSO-d6) δ 165.38, 152.69, 145.72, 144.37, 129.08, 121.60, 113.95, 71.02, 63.79,
21.47. HRMS-ESI: calculated for [M]+ (C11H13NO6): m/z 254.0665 found: m/z 254.0659.
Compound 1o: 2-hydroxy-5-methylbenzoic acid (2.00 g, 13.0 mmol) was dissolved in MeOH (40 mL), to
which concentrated H2SO4 (5 mL) was added. The mixture was heated under reflux for 48 hrs. The solvent
was then removed in vacuo and the residue was dissolved in CH2Cl2 (100 mL), washed with water (2 x 50
mL) and dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the pure ester which could directly used for
the next step. The ester (0.17 g, 1.00 mmol) was dissolved in 20ml CH2Cl2, to which concentrated (69%)
0
HNO3 (0.10 mL, 1.56 mmol) was added with stirring at -20 C. Concentrated (95%) H2SO4 (0.20 mL, 2.74
mmol) was then added dropwise to the reaction mixture. After 20 min, the reaction was quenched with 50 mL
of distilled water. The CH2Cl2 layer was washed with water (2 x 50 mL) and dried over anhydrous Na2SO4.
1
Removal of CH2Cl2 gave the pure product 1o as a yellow solid. Yield: 1.00 g, 80%. H NMR (300 MHz,
CDCl3) δ 11.74 (s, 1H), 7.98 (s, 1H), 7.95 (s, 1H), 4.00 (s, 1H), 2.37 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
169.76, 154.29, 147.91, 136.95, 135.21, 132.26, 129.00, 53.71, 20.86. HRMS-ESI: calculated for [M]+
(C9H9NO5): m/z 210.0402 found: m/z 210.0404.
Compound 1p: 1o (1.00 g, 4.73 mmol) was dissolved in anhydrous DMF (15 mL), to which anhydrous
K2CO3 (2.60 g, 19.0 mmol) and iodomethane (0.75 mL, 12.0 mmol) was added. The mixture was heated
under 60 0C for 4 hrs. CH2Cl2 (50 mL) was then added and the reaction mixture was filtered. The solvent was
removed in vacuo and the concentrate was dissolved in CH2Cl2 (50 mL), washed with water (2 x 50 mL) and
dried over anhydrous Na2SO4. Removal of CH2Cl2 gave the pure product as white solid 1p. Yield: 1.01 g,
1
83%. H NMR (300 MHz, CDCl3) δ 7.82 (s, 1H), 7.71 (s, 1H), 3.96 (s, 3H), 3.95 (s, 3H), 2.40 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 165.72, 151.75, 145.83, 136.72, 134.84, 129.33, 127.72, 64.92, 53.41, 21.20.
HRMS-ESI: calculated for [M]+ (C10H11NO5): m/z 224.0553 found: m/z 224.0550.
Compound 1q: 1p (1.00 g, 4.40 mmol) was dissolved in hot MeOH (20 mL), to which 1N NaOH (10 mL,
10.0 mmol) was added. The mixture was heated under reflux for 1 h and then more water (50 mL) was added.
The aqueous layer was neutralized by addition of 1M HCl (15 mL). The precipitated crude product was
collected by filtration, which was recrystallized from MeOH to give a white solid 1q. Yield: 0.51 g, 59%. 1H
NMR (300 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.83 (s, 1H), 3.84 (s, 3H), 2.36 (s, 3H). 13C NMR (125 MHz,
S5

DMSO-d6) δ 165.64, 149.20, 144.75, 135.29, 134.36, 127.72, 127.58, 63.64, 19.75. HRMS-ESI: calculated
for [M]+ (C9H9NO5): m/z 210.0402 found: m/z 210.0400.
Compound 1r: Salicylic acid (10.0 g, 72.5 mmol) was dissolved in 200mL of CH2Cl2, to which concentrated
HNO3 (69%, 6.05 mL, 94.2 mmol) was added with stirring at 0 0C. Concentrated H2SO4 (95%, 10.6 mL, 145
mmol) was then added dropwise to the reaction mixture. After 20 min, the reaction was quenched with 500
mL of distilled water and the mixture was filtered. The yellow residue was then dried under IR lamp for at
least 30 min. The crude product was directly used in the next step without further purification. Crude
compound (20.0 g) was dissolved in methanol (260 mL), to which concentrated H2SO4 (21.9 mL, 388 mmol)
was added. The mixture was heated under reflux for 48 hrs. The solvent was then removed in vacuo and the
residue was dissolved in CH2Cl2 (200 mL), washed with water (2 x 100 mL), finally washed with aq NaHCO3
(100 mL) and dried over anhydrous Na2SO4. Removal of CH2Cl2 gave a yellow solid which was purified by
flash column chromatography (silica gel) using hexane/ CH2Cl2 (4:1) as the eluent to give pure product 1r as
a bright yellow solid. Overall Yield: 14.3 g, 72%. 1H NMR (300 MHz, CDCl3) δ 11.99 (s, 1H), 8.15 (m, 2H),
7.01 (m, 1H), 4.02 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 169.16, 155.59, 137.97, 135.67, 131.30, 118.34,
115.78, 53.10. (Ref: Dumn, B.M.; Bruice, T. C. J. Am. Chem. Soc. 1970, 92, 2410)
Compound 1s: 1r (6.00 g, 30.4 mmol) was dissolved in DMF (125 mL) to which anhydrous K2CO3 (15.6 g,
113 mmol) and iodomethane (6.98 mL, 112 mmol) were added to it. The mixture was heated under reflux for
4 hrs. The reaction mixture was then filtered and the solvent was removed in vacuo. The residue was
dissolved in CH2Cl2 (100 mL), washed with water (2 x 50 mL), and dried over anhydrous Na2SO4. Removal
of CH2Cl2 gave a pure light yellow solid 1s. Yield: 6.41 g, 82%. 1H NMR (300 MHz, CDCl3) δ 8.03 (m, 1H),
8.00 (m, 1H), 7.91 (d, 1H, J = 1.8), 3.99 (s, 3H), 3.94 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.42, 152.86,
145.17, 135.25, 128.02, 127.06, 123.50, 63.89, 52.39. HRMS-ESI: calculated for [M]+ (C8H7NO5): m/z
211.0481 found: m/z 211.0480.
Compound 1t: 1s (4.00 g, 19.0 mmol) was dissolved in hot methanol (10 mL) to which 1M NaOH (40 mL,
40.0 mmol) was added. The mixture was heated under reflux for 2 h and then quenched with water (100 mL).
The aqueous layer was neutralized by addition of 1M HCl (80 mL) until the pH was at least 1. The
precipitated crude product was collected by filtration, which was recrystallized from hot methanol to give a
pure white solid 1t. Yield: 3.45 g, 92%. 1H NMR (300 MHz, CDCl3) δ 8.28 (m, 1H), 8.03 (m, 1H), 7.36 (m,
1H), 4.08 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 164.97, 151.89, 144.49, 134.71, 127.31, 126.79, 122.79,
63.06. (Ref: Lloyd, H. A.; Warren, K. S.; Fales, H. M. J. Am, Chem. Soc. 1966, 88, 5544)
0
Compound 2a: 1s (3.16 g, 15.0 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd/C (0.30 g, 10%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure brown liquid. The resulting amine was immediately used for the next
coupling. Acid 1t (3.00 g, 15.2 mmol) was dissolved in CH2Cl2 (30 mL) to which 4-methylmorpholine
(NMM (2.20 mL, 17.9 mmol) and ethyl chloroformate (1.96 mL, 16.4 mmol) was added at 0 0C. The reaction
mixture was stirred for at least 15 min then a solution of above amine (2.70 g, 14.9 mmol) dissolved in
CH2Cl2 (30 mL) was added. The reaction mixture was allowed to stir continuously overnight at room
(
temperature. The reaction mixture was washed with 1M KHSO4 100 mL), followed by saturated NaHCO3
S6

(100 mL) and saturated NaCl (100 mL). Drying over Na2SO4 and removal of solvent in vacuo gave the crude
product, which was recrystallized from methanol to give the pure product 2a as a white solid. Yield: 3.49 g,
71%. 1H NMR (300 MHz, CDCl3) δ 10.37 (s, 1H), 8.80 (d, 1H, J = 8.2), 8.44 (d, 1H, J = 8.2), 7.99 (d, 1H, J
= 7.9), 7.63 (d, 1H, J = 8.1), 7.41 (t, 1H, J = 8.1), 7.24 (t, 1H, J = 8.1), 4.10 (s, 3H), 3.95 (s, 6H). 13C NMR
(125 MHz, CDCl3) δ 165.85, 161.27, 151.46, 149.43, 136.47, 132.70, 128.75, 126.56, 124.60, 123.51, 64.47,
62.57. HRMS-ESI: calculated for [M+Na]+ (C17H16N2O7Na): m/z 383.0850 found: m/z 383.0856.
0
Compound 3a: 2a (3.46 g, 10.0 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd-C (0.35 g, 10%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1t (2.06 g,
10.5 mmol) was dissolved in CH2Cl2 (50 mL) to which NMM (1.35 mL, 12.4 mmol) and ethyl chloroformate
(1.08 mL, 11.3 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min after which a
solution of the above amine (3.10 g, 9.04 mmol) dissolved in CH2Cl2 (50 mL) was added. The reaction
mixture was allowed to stir continuously overnight at room temperature. The reaction mixture was washed
with 1M KHSO4 (100 mL), followed by saturated NaHCO3 (100 mL) and saturated NaCl (100 mL). Drying
over Na2SO4 and removal of solvent in vacuo gave the crude product, which was recrystallized from
1
methanol to give the pure product 3a as a white solid. Yield: 3.64 g, 82%. H NMR (300 MHz, CDCl3) δ
10.25 (s, 1H), 10.23 (s, 1H), 8.85 (d, 1H, J = 7.9), 8.78 (d, 1H, J = 7.9), 8.47 (d, 1H, J = 7.9), 8.03 (d, 1H, J =
8.0), 7.91 (d, 1H, J = 7.9), 7.62 (d, 1H, J = 7.9), 7.40 (m, 2H), 7.22 (m, 1H), 4.14 (s, 3H), 3.98 (s, 3H), 3.96 (s,
6H). 13C NMR (75 MHz, CDCl3) δ 162.81, 161.33, 151.34, 149.23, 147.29, 144.32, 136.59, 133.03, 131.97,
129.09, 128.97, 126.73, 126.63, 126.22, 125.79, 125.05, 124.71, 124.59, 124.42, 123.45, 64.45, 63.23, 62.50,
53.38, 52.30. HRMS-ESI: calculated for [M+Na]+ (C25H23N3O9): m/z 532.1327 found: m/z 532.1328.
0
Compound 4a: 3a (3.00 g, 6.09 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd-C (0.60 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1t (1.79 g,
9.10 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (50 mL) and DMF (0.42 mL) were added to the acid, followed by dropwise addition of oxalyl
chloride, (COCl)2, (1.05 mL, 7.27 mmol). The reaction mixture was allowed to stir for 2 hrs. The solvent was
then removed in vacuo and saturated with nitrogen gas before addition of 15 mL dry CH2Cl2. The above
amine (2.81 g, 6.06 mmol) was dissolved in 35 mL dry CH2Cl2 and triethylamine (TEA, 1.86 mL, 12.1 mmol)
0
before addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 2 hrs and then
was washed with aq NaHCO3 (100 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo
gave the crude product, which was recrystallized from methanol to give the pure product 4a as a white solid.
Yield: 2.34 g, 61%. 1H NMR (500 MHz, CDCl3) δ 10.20 (s, 1H), 10.10 (s, 1H), 10.00 (s, 1H), 8.76 (m, 3H),
8.44 (m, 1H), 8.03 (m, 1H), 7.90 (m, 2H), 7.61 (m, 1H), 7.40 (m, 3H), 7.22 (m, 1H), 4.13 (s, 3H), 3.97 (s, 3H),
3.95 (s, 3H), 3.94 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.80, 162.86, 161.42, 151.21, 149.19, 147.17,
144.29, 136.39, 132.58, 131.86, 129.20, 128.57, 126.69, 126.57, 126.28, 126.14, 125.67, 124.63, 123.41,
64.40, 63.07, 62.37, 52.26. HRMS-ESI: calculated for [M+Na]+ (C33H30N4O11Na): m/z 681.1803 found: m/z
681.1791.
S7

0
Compound 2h: 4a (0.61 g, 0.95 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 50 C,
using Pd-C (0.75 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1t (0.27 g,
1.36 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (5 mL) and DMF (60 μL) were added to the acid, followed by dropwise addition of oxalyl
chloride (142 μL, 1.12 mmol). The reaction mixture was allowed to stir for 2 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.57 g, 0.93 mmol) was dissolved in 25 mL dry CH2Cl2 and triethylamine, triethylamine (0.27 mL, 1.86
mmol) before addition to the reaction mixture above. The reaction mixture was stirred at 50 0C for 2 hrs and
then was washed with aq NaHCO3 (50 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo
gave the crude product which was recrystallised from methanol and further purified by flash column
chromatography (silica gel as the stationary phase) using CH2Cl2/CH3CN (10:1) as the eluent to give pure
1
product 5a as a white solid. Yield: 0.44 g, 61%. H NMR (300 MHz, CDCl3) δ 10.25 (d, 2H), 9.85 (s, 1H),
9.65 (s, 1H), 8.81 (m, 4H), 8.44 (m, 1H), 8.02 (m, 4H), 7.89 (m, 2H), 7.61 (m, 4H), 4.03 (s, 15H), 3.88 (m,
3H). 13C NMR (125 MHz, CDCl3) δ 165.56, 163.06, 162.81, 161.42, 151.25, 149.22, 147.24, 147.19, 144.14,
136.40, 132.17, 131.91, 128.84, 126.49, 125.69, 124.75, 123.25, 64.38, 63.14, 62.97, 52.10. HRMS-ESI:
calculated for [M+Na]+ (C41H37N3O13Na): m/z 830.2280 found: m/z 830.2304.
Compound 2h: 2a (1.00 g, 2.78 mmol) was dissolved in hot methanol (20 mL) to which 1M KOH (10 mL,
10.0 mmol) and KCl (0.98 g, 10.0 mmol) was added. The mixture was heated under reflux for 2 h and then
quenched with water (50 mL). The aqueous layer was neutralized by addition of 1M HCl (15 mL) until pH =
1. The precipitated crude product was collected by filtration, which was recrystallized from hot methanol to
give a pure white solid 2g. Yield: 0.80 g, 83%. 1H NMR (300 MHz, CDCl3) δ 10.39 (s, 1H), 8.93 (d,1H, J =
8.2), 8.45 (d, 1H, J = 7.6), 8.00 (d, 1H, J = 7.6), 7.77 (d, 1H, J = 7.6), 7.43 (s, 1H), 7.31 (m, 1H), 4.10 (s, 3H),
4.03 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δ 167.32, 163.39, 150.76, 150.58, 144.40, 135.00, 132.52,
131.59, 127.79, 127.09, 126.37, 126.16, 125.14, 124.17. HRMS-ESI: calculated for [M+Na]+
(C16H14N2O7Na): m/z 345.0723 found: m/z 345.0714.
0
Compound 6a: 4a (0.36 g, 0.55 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 50 C,
using Pd-C (0.070 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 2h (0.22 g,
0.66 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (5 mL) and DMF (40 μL) were added to the acid, followed by dropwise addition of oxalyl
chloride (100 μL, 0.79 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.32 g, 0.51 mmol) was dissolved in 15 mL dry CH2Cl2 and triethylamine (0.15 mL, 1.02 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (30 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was purified by flash column chromatography (silica gel as the stationary phase) using
CH2Cl2 / CH3CN (10:1) as the eluent to give pure product 6a as a white solid. Yield: 0.12 g, 19%. 1H NMR
(500 MHz, CDCl3) δ 10.28 (s, 1H), 10.19 (s, 1H), 10.15 (s, 1H), 10.12 (s, 1H), 9.84 (s, 1H), 8.85 (m, 2H),
S8

8.80 (m, 3H), 8.33 (d, 1H, J = 7.8) 7.82 (m, 5H), 7.51 (d, 1H, J = 7.8), 7.39 (m, 5H), 7.15 (d, 1H), 4.08 (s,
3H), 4.04 (s, 3H), 4.02 (s, 3H), 4.01 (s, 3H), 3.96 (s, 3H), 3.79 (s, 6H). 13C NMR (125 MHz, CDCl3) δ 165.36,
163.34, 163.04, 162.93, 162.82, 161.32, 151.00, 149.09, 147.21, 147.19, 147.08, 144.10, 136.37, 133.12,
132.34, 132.16, 132.03, 129.06, 128.80，126.79，126.65, 126.55，126.47, 126.36, 126.31, 126.18，126.03,
125.97, 125.92, 125.84, 125.35, 125.13, 124.99, 124.88, 124.84, 124.68, 124.43, 123.10, 64.46, 63.26, 63.10,
63.00, 62.97, 62.25, 52.23. HRMS-ESI: calculated for [M+Na]+ (C49H44N6O15Na): m/z 979.2957 found: m/z
979.2765.
0
Compound 2b: 1h (1.70 g, 8.00 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd/C (0.17 g, 10%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure brown liquid. The resulting amine was immediately used for the next
coupling. Acid 1t (2.00 g, 10.1 mmol) was dissolved in CH2Cl2 (30 mL) to which NMM (2.00 mL, 18.3
mmol) and ethyl chloroformate (1.50 mL, 12.6 mmol) was added at 0 0C. The reaction mixture was stirred for
at least 15 min then a solution of above amine dissolved in CH2Cl2 (30 mL) was added. The reaction mixture
was allowed to stir continuously overnight at room temperature. The reaction mixture was washed with 1M
KHSO4 (100 mL), followed by saturated NaHCO3 (100 mL) and saturated NaCl (100 mL). Drying over
Na2SO4 and removal of solvent in vacuo gave the crude product, which was recrystallized from methanol to
give the pure product 2b as a white solid. Yield: 2.40 g, 77%. 1H NMR (500 MHz, CDCl3) δ 10.35 (s, 1H),
8.47 (d, 1H, J = 3.2), 8.43 (d, 1H, J = 8.1), 7.98 (d, 1H, J = 7.8), 7.40 (t, 1H, J = 8.1), 7.13 (d, 1H, J = 3.2),
4.08 (s, 3H), 3.94 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.67, 161.29, 155.59,
151.48, 144.36, 143.30, 136.43, 133.40, 129.08, 128.80, 124.81, 123.76, 111.00, 110.73, 64.47, 62.57, 55.84,
52.39. HRMS-ESI: calculated for [M]- (C18H18N2O8): m/z 389.0990 found: m/z 389.0985.
Compound 2d: 1h (0.60 g, 2.49 mmol) was reduced by catalytic hydrogenation in THF (15 mL) at 40 0C for
3 h. The resulting amine was dissolved in CH2Cl2 (30 mL) was immediately used for the next coupling. Acid
1k (0.74 g, 3.24 mmol) was dissolved in CH2Cl2 (30 mL) to which NMM (0.45 mL, 3.68 mmol) and ethyl
chloroformate (0.40 mL, 3.34 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (30 mL), followed by
saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of solvent in
vacuo gave the crude product, which was recrystallized from methanol to give the pure product 2d as a
yellow solid. Yield: 0.75 g, 72%. 1H NMR (300 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.10 (d, 1H, J = 3.3), 7.70
(d, 1H, J = 3.3), 7.61 (d, 1H, J = 3.5), 7.04 (d, 1H, J = 3.1), 3.87 (m, 15H).δ 10.37 (s, 1H), 8.80 (d, 1H, J =
6.57), 8.44 (d, 1H, J = 6.09), 7.99 (d, 1H, J = 6.24), 7.63 (d, 1H, J = 6.27), 7.43 (m, 2H), 4.10 (s, 3H), 3.95 (s,
6H). 13C NMR (125 MHz, CDCl3) δ 155.52, 144.72, 143.28, 133.37, 129.59, 123.74, 120.63, 111.64, 111.05,
110.62, 64.60, 62.65, 56.27, 55.81, 52.38. HRMS-ESI: calculated for [M+Na]+ (C19H20N2O9Na): m/z
443.1061 found: m/z 443.1065.
Compound 2e: 1h (0.50 g, 2.37 mmol) was reduced by catalytic hydrogenation in THF (15 mL) at 60 0C for
3 h. The resulting amine was dissolved in CH2Cl2 (30 mL) was immediately used for the next coupling. Acid
1k (0.90 g, 2.84 mmol) was dissolved in CH2Cl2 (30 mL) to which NMM (0.45 mL, 3.68 mmol) and ethyl
S9

chloroformate (0.40 mL, 3.26 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (30 mL), followed by
saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of solvent in
vacuo gave the crude product, which was recrystallized from methanol to give the pure product 2e as a yellow
solid. Yield: 0.90 g, 73%. 1H NMR (300 MHz, DMSO-d6) δ 10.49 (s, 1H), 8.48 (d, 1H, J = 3.2), 7.94 (d, 1H,
J = 3.2), 7.49 (d, 1H, J = 3.2), 7.14 (d, 1H, J = 3.2), 4.03 (m, 2H), 4.02 (s, 3H), 3.94 (s, 3H), 3.89 (s, 3H),
3.86 (s, 3H) 1.81 (m, 2H), 1.35 (m, 10H), 0.92 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 165.67, 161.27,
155.54, 155.18, 144.72, 144.64, 143.31, 133.43, 129.50, 123.78, 121.14, 115.09, 111.02, 110.64, 69.29, 64.59,
62.66, 55.81, 52.37, 31.75, 30.87, 29.21, 28.91, 25.85, 22.61, 14.05. HRMS-ESI: calculated for [M+Na]+
(C26H34N2O9Na): m/z 541.2157 found: m/z 541.2152.
0
Compound 3b: 2b (1.05 g, 2.70 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 40 C,
using Pd-C (0.16 g, 15%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1t (0.74 g,
3.30 mmol) was dissolved in CH2Cl2 (20 mL) to which NMM (0.50 mL, 4.06 mmol) and ethyl chloroformate
0
(0.40 mL, 3.33 mmol) was added at 0 C. The reaction mixture was stirred for at least 15 min after which a
solution of the above amine dissolved in CH2Cl2 (20 mL) was added. The reaction mixture was allowed to stir
continuously overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (30 mL),
followed by saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of
solvent in vacuo gave the crude product, which was recrystallized from methanol to give the pure product 3b
as a white solid. Yield: 1.20 g, 78%. 1H NMR (300 MHz, CDCl3) δ 10.38 (s, 1H), 10.25 (s, 1H), 8.78 (d, 1H,
J = 8.4), 8.54 (d, 1H, J = 2.8), 7.99 (d, 1H, J = 3.5), 7.91 (d, 1H, J = 8.0), 7.54 (d, 1H, J = 3.2), 7.37 (t, 1H, J
= 7.9), 7.14 (d, 1H, J = 3.2), 4.07 (s, 3H), 3.97 (s, 3H), 3.95 (s, 3H), 3.93 (s, 3H), 3.90 (s, 3H), 3.89 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 161.16, 155.60, 147.29, 144.65, 133.66, 131.95, 129.52, 126.62, 125.71,
124.65, 123.64, 120.81, 114.63, 110.75, 110.41, 64.50, 63.19, 62.53, 56.27, 55.78, 52.32. HRMS-ESI:
calculated for [M]+ (C27H27N3O11Na): m/z 592.1538 found: m/z 592.1534.
0
Compound 3c: 2d (0.31 g, 0.74 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd-C (0.040 g, 10%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1t (0.22 g,
0.96 mmol) was dissolved in CH2Cl2 (10 mL) to which NMM (0.15 mL, 1.95 mmol) and ethyl chloroformate
0
(0.12 mL, 1.43 mmol) was added at 0 C. The reaction mixture was stirred for at least 15 min after which a
solution of the above amine dissolved in CH2Cl2 (10 mL) was added. The reaction mixture was allowed to stir
continuously overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (20 mL),
followed by saturated NaHCO3 (20 mL) and saturated NaCl (20 mL). Drying over Na2SO4 and removal of
solvent in vacuo gave the crude product, which was recrystallized from methanol to give the pure product 3c
as a white solid. Yield: 0.37 g, 83%. 1H NMR (300 MHz, CDCl3) δ 10.39 (s, 2H), 8.54 (d, 1H, J = 3.2), 8.44
(d, 1H, J = 3.2), 7.98 (d, 1H, J = 3.2), 7.54 (d, 1H, J = 3.2), 7.44 (d, 1H, J = 3.2), 7.14 (d, 1H, J = 3.2), 4.06 (s,
3H), 3.95 (s, 3H), 3.92 (s, 9H) 3.90 (s, 3H), 3.86 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.73, 162.62,
161.18, 156.75, 155.67, 144.72, 143.07, 141.21, 133.75, 132.73, 129.53, 126.70, 125.02, 123.74, 122.06,
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120.76, 120.19, 117.42, 114.81, 111.17, 110.91, 110.39, 64.57, 63.42, 62.58, 56.34, 55.88, 55.84, 52.39.
HRMS-ESI: calculated for [M+Na]+ (C28H29N3O12Na): m/z 622.1643 found: m/z 622.1646.
Compound 3d: 2e (0.90 g, 1.84 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 60 0C for
3 h. The resulting amine was dissolved in CH2Cl2 (30 mL) was immediately used for the next coupling. Acid
1k (0.60 g, 2.64 mmol) was dissolved in CH2Cl2 (30 mL) to which NMM (0.40 mL, 3.25 mmol) and ethyl
chloroformate (0.35 mL, 2.92mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (30 mL), followed by
saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of solvent in
vacuo gave the crude product, which was recrystallized from methanol to give the pure product 3d as a
yellow solid. Yield: 0.86 g, 67%. 1H NMR (300 MHz, CDCl3) δ 10.39 (s, 1H), 10.37 (s, 1H), 8.54 (d, 1H, J =
3.2), 8.41 (d, 1H, J = 3.2), 7.98 (d, 1H, J = 3.2), 7.53 (d, 1H, J = 3.5), 7.42 (d, 1H, J = 3.2), 7.13 (d, 1H, J =
3.2), 4.06 (s, 3H), 4.03 (m, 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H), 3.86 (s, 3H) 1.78 (m, 2H), 1.31 (m,
10H), 0.85 (m, 3H). 13C NMR (500 MHz, CDCl3) δ 162.67, 161.13, 156.31, 155.71, 155.63, 144.68, 143.04,
141.02, 133.76, 132.60, 129.55, 126.59, 123.70, 120.75, 114.73, 111.69, 110.92, 110.84, 110.37, 68.69, 64.53,
63.38, 62.55, 56.30, 55.81, 52.36, 31.78, 29.28, 29.20,29.14, 15.95, 22.62, 14.06. HRMS-ESI: calculated for
[M]+ (C35H43N3O12): m/z 720.2739 found: m/z 720.2757.
Compound 1u: 1k (0.40 g, 1.76 mmol), isopropamine (0.14 g, 2.37 mmol) was dissolved in CH2Cl2 (30 mL),
to which EDC (0.50 g, 2.60 mmol) and HOBT (0.50 g, 3.70 mmol) was added. The reaction mixture was
stirred for overnight at room temperature. The rection mixture was washed with 1M KHSO4 (30 mL),
followed by saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of
solvent in vacuo gave the product 1u. Yield: 0.45 g, 95%. 1H NMR (300 MHz, CDCl3) δ 7.79 (d, 1H, J = 3.2),
7.41 (d, 1H, J = 3.2), 7.30 (s, 1H), 3.90 (s, 1H), 3.87 (s, 1H), 1.28 (s, 3H), 1.27 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 163.01, 156.24, 145.04, 143.44, 131.38, 121.15, 114.16, 64.59, 57.59, 56.90, 46.15, 45.53, 42.55.
HRMS-EI: calculated for [M]+ (C8H8O4): m/z 268.1059 found: m/z 268.1055.
Compound 2f: 1u (0.45 g, 1.68 mmol) was reduced by catalytic hydrogenation in THF (30 mL) at 40 0C for
3 h. The resulting amine was dissolved in CH2Cl2 (40 mL) was immediately used for the next coupling. Acid
1l (0.74 g, 2.24 mmol) was dissolved in CH2Cl2 (40 mL) to which NMM (0.40 mL, 3.27 mmol) and ethyl
chloroformate (0.30 mL, 2.45 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (30 mL), followed by
saturated NaHCO3 (30 mL) and saturated NaCl (30 mL). Drying over Na2SO4 and removal of solvent in
vacuo gave the crude product, which was recrystallized from methanol to give the pure product 2f as a yellow
solid. Yield: 0.35g, 64%. 1H NMR (300 MHz, CDCl3) δ 10.24 (s, 1H), 8.34 (d, 1H, J = 3.2), 7.92 (d, 1H, J =
3.2), 7.50 (d, 1H, J = 3.9), 7.26 (d, 1H, J = 3.2), 7.22 (d, 1H, J = 3.2), 4.33 (m, 1H), 4.03 (s, 5H), 3.82 (s, 6H),
1.80 (m, 2H), 1.24 (m, 16H), 0.88 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 164.44, 161.88, 157.14, 155.99,
145.33, 145.13, 141.52, 133.07, 130.33, 128.14, 121.89, 115.76, 110.88, 110.66, 69.99, 65.33, 63.24, 56.48,
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42.24, 32.43, 29.89, 29.85, 29.59, 26.53, 23.29, 14.74. HRMS-ESI: calculated for [M]- (C28H39N3O8): m/z
544.2664 found: m/z 544.2680.
0
Compound 2c: 1s (1.60 g, 8.80 mmol) was reduced by catalytic hydrogenation in THF (50 mL) at 40 C,
using Pd-C (0.16 g, 10%) as the catalyst for 3 h. The resulting amine was dissolved in CH2Cl2 (60 mL) was
immediately used for the next coupling. Acid 1l (3.44 g, 10.6 mmol) was dissolved in CH2Cl2 (90 mL) to
0
which NMM (1.40 mL, 11.2 mmol) and ethyl chloroformate (1.50 mL, 12.2 mmol) was added at 0 C. The
reaction mixture was stirred for at least 15 min then the solution of above amine was added. The reaction
mixture was allowed to stir continuously overnight at room temperature. The reaction mixture was washed
with 1M KHSO4 (100 mL), followed by saturated NaHCO3 (100 mL) and saturated NaCl (100 mL). Drying
over Na2SO4 and removal of solvent in vacuo gave the crude product, which was purified by flash column
chromatography (silica gel) using hexane/ethyl acetate (8:1 v/v) as the eluent to give pure yellow solid 2c.
Yield: 2.00 g, 47%. 1H NMR (300 MHz, CDCl3) δ 10.46 (s, 1H), 8.77 (d, 1H, J = 5.1), 7.93 (d, 1H, J = 3.5),
7.61 (d, 1H, J = 8.9), 7.48 (d, 1H, J = 3.5), 7.21 (m, 1H), 4.02 (m, 2H), 3.94 (s, 6H), 1.81 (m, 2H), 1.44 (m,
2H), 1.30 (m, 8H), 0.84 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 165.84, 161.22, 155.17, 149.45, 144.70,
144.61, 132.74, 129.60, 126.50, 124.55, 124.23, 123.52, 121.27, 114.94, 69.26, 64.56, 62.55, 52.31, 31.74,
29.20, 29.15, 28.91, 25.85, 22.60, 14.04. HRMS-ESI: calculated for [M+Na]+ (C25H32N2O8Na): m/z 511.2051
found: m/z 511.2038
0
Compound 3e: 2c (1.00 g, 2.18 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 40 C,
using Pd-C (0.10 g, 10%) as the catalyst for 3 h. The resulting amine was dissolved in CH2Cl2 (20 mL) was
immediately used for the next coupling. Acid 1m (0.70 g, 2.75 mmol) was dissolved in CH2Cl2 (30 mL) to
0
which NMM (0.40 mL, 3.25 mmol) and ethyl chloroformate (0.35 mL, 2.93 mmol) was added at 0 C. The
reaction mixture was stirred for at least 15 min then the solution of above amine was added. The reaction
0
mixture was allowed to stir continuously overnight at 50 C. The reaction mixture was washed with 1M
KHSO4 (50 mL), followed by saturated NaHCO3 (50 mL) and saturated NaCl (50 mL). Drying over Na2SO4
and removal of solvent in vacuo gave the crude product, which was purified by flash column chromatography
(silica gel) using hexane/ethyl acetate (5:1 v/v) as the eluent to give pure yellow solid 3e. Yield: 1.00 g, 52%.
1H NMR (300 MHz, CDCl3) δ 10.37 (s, 1H), 10.36 (s, 1H), 8.84 (d, 1H, J = 3.2), 8.42 (d, 1H, J = 3.3), 7.94
(d, 1H, J = 3.2), 7.60 (d, 1H, J = 1.7), 7.50 (d, 1H, J = 3.2), 7.42 (d, 1H, J = 3.2), 7.24 (m, 1H), 4.65 (m, 1H),
4.06 (s, 3H), 4.05 (m, 2H), 3.96 (s, 3H), 3.95 (s, 3H), 3.91 (s, 3H), 1.83 (m, 2H), 1.54 (s, 6H), 1.40 (m, 8H),
1.24 (m, 2H), 0.88 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 165.89, 162.64, 161.24, 156.31, 154.17, 149.22,
144.77, 144.33, 141.00, 133.08, 132.62, 129.51, 126.71, 126.10, 124.52, 124.33, 123.50, 122.25, 116.26,
111.58, 111.04, 71.56, 68.65, 64.47, 63.33, 62.43, 52.27, 31.77, 29.27, 29.16, 25.95, 22.61, 21.73, 14.03.
HRMS-ESI: calculated for [M]+ (C36H45N3O11): m/z 718.2946 found: m/z 718.2952.
0
Compound 4b: 3e (0.84 g, 1.20 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 40 C,
using Pd-C (0.17 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1q (0.30 g,
1.42 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (8 mL) and DMF (64 μL) were added to the acid, followed by dropwise addition of oxalyl
S12

chloride (0.16 mL, 1.26 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.80 g, 1.20 mmol) was dissolved in 15 mL dry CH2Cl2 and triethylamine (0.60 mL, 4.2 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (50 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
(silica gel as the stationary phase) using hexane/ethyl acetate (2:1 v/v) as the eluent to give pure 4b as white
solid. Yield: 0.59 g, 57%. 1H NMR (300 MHz, CDCl3) δ 10.33 (s, 1H), 10.14 (s, 1H), 10.10 (s, 1H), 8.84 (d,
1H, J = 7.0), 8.46 (d, 1H, J = 2.8), 8.41 (d, 1H, J = 3.2), 8.23 (d, 1H, J = 1.7), 7.83 (d, 1H, J = 1.7), 7.61 (d,
1H, J = 7.0), 7.42 (m, 2H), 7.23 (m, 1H), 4.66 (m, 1H), 4.09 (s, 3H), 4.05 (m, 2H), 3.96 (s, 3H), 3.94 (s, 6H),
3.91 (s, 3H), 2.48 (s, 3H), 1.84 (m, 2H), 1.48 (s, 6H), 1.39 (m, 8H), 1.22 (m, 2H), 0.87 (m, 3H). 13C NMR (75
MHz, CDCl3) δ 165.92, 162.79, 162.74, 161.64, 156.33, 155.17, 149.26, 149.03, 143.98, 140.85, 136.83,
135.67, 133.08, 132.93, 132.66, 129.13, 128.63, 126.74, 126.60, 126.18, 126.04, 124.68, 124.40, 123.44,
113.06, 112.39, 111.42, 111.08, 110.80, 70.74, 68.62, 64.40, 63.31, 63.24, 62.42, 52.37, 31.80, 29.66, 29.30,
29.22, 29.17, 25.97, 22.64, 21.97, 20.68, 14.09. HRMS-ESI: calculated for [M+Na]+ (C45H54N4O13Na): m/z
881.3580 found: m/z 881.3572.
0
Compound 5b: 4b (0.40 g, 0.47 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 50 C,
using Pd-C (0.08 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1m (0.24
g, 0.94 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (8 mL) and DMF (40 μL) were added to the acid, followed by dropwise addition of oxalyl
chloride (0.10 mL, 0.78 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.39 g, 0.47 mmol) was dissolved in 10 mL dry CH2Cl2 and triethylamine (0.40 mL, 2.8 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (50 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
(silica gel as the stationary phase) using hexane/ethyl acetate (2:1 v/v) as the eluent to give pure 5b as yellow
solid. Yield: 0.23 g, 46%. 1H NMR (300 MHz, CDCl3) δ 10.35 (s, 1H), 10.22 (s, 1H), 10.10 (s, 1H), 9.86 (s,
1H), 8.82 (d, 1H, J = 8.2), 8.61 (d, 1H, J = 1.7), 8.43 (m, 2H), 7.91 (d, 1H, J = 3.3), 7.68 (d, 1H, J = 4.7), 7.59
(d, 1H, J = 1.7), 7.47 (d, 1H, J = 3.3), 7.39 (m, 2H), 7.20 (m, 1H), 4.64 (m, 1H), 4.05 (s, 3H), 4.04 (m, 2H),
3.97 (s, 3H), 3.94 (s, 3H), 3.90 (s, 3H), 3.86 (s, 3H), 3.84 (s, 3H), 2.45 (s, 3H), 1.79 (m, 2H), 1.47 (s, 6H),
1.37 (m, 2H), 1.28 (m, 8H), 0.86 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 165.61, 163.24, 162.89, 162.75,
161.41, 156.32, 155.18, 154.18, 149.32, 145.14, 144.67, 144.32, 140.98, 140.80, 135.88, 133.12, 132.94,
131.61, 129.76, 126.83, 126.78, 126.61, 126.24, 126.10, 125.40, 124.72, 124.38, 123.33, 122.27, 119.88,
116.22, 113.02, 112.27, 111.89, 111.61, 110.91, 71.56, 70.74, 68.64, 64.45, 63.14, 62.27, 31.76, 29.62, 29.27,
29.17, 25.95, 22.60, 21.98, 21.70, 21.30, 14.01. HRMS-ESI: calculated for [M+Na]+ (C56H67N5O16Na): m/z
1088.4755 found: m/z 1088.4750.
S13

0
Compound 5c: 4b (0.20 g, 0.24 mmol) was reduced by catalytic hydrogenation in THF (10 mL) at 50 C,
using Pd-C (0.040 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1q (0.10 g,
0.47 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (5 mL) and DMF (20 μL) were added to the acid, followed by dropwise addition of oxalyl
chloride (0.060 mL, 0.50 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.19 g, 0.24 mmol) was dissolved in 5 mL dry CH2Cl2 and triethylamine (0.20 mL, 1.40 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (20 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
(silica gel as the stationary phase) using hexane/ethyl acetate (2:1 v/v) as the eluent to give pure 5c as yellow
1
solid. Yield: 0.12 g, 49%. H NMR (500 MHz, CDCl3) δ 10.28 (s, 1H), 10.21 (s, 1H), 9.95 (s, 1H), 9.84 (s,
1H), 8.83 (d, 1H, J = 8.2), 8.79 (m, 3H), 7.92 (d, 1H, J = 3.1), 7.90 (m, 3H), 7.61 (d, 1H, J = 7.9), 7.49 (d,
1H, J = 3.1), 7.40 (m, 3H), 7.20 (m, 1H), 4.65 (m, 1H), 4.06 (s, 3H), 4.02 (s, 6H), 3.96 (s, 3H), 3.89 (s, 3H),
3.88 (s, 3H), 1.38 (s, 6H). 1H NMR (500 MHz, CDCl3) δ 10.35 (s, 1H), 10.10 (s, 2H), 9.85 (s, 1H), 8.83 (d,
1H, J = 8.2), 8.60 (d, 1H, J = 1.7), 8.43 (m, 2H), 8.22 (d, 1H, J = 3.3), 7.79 (d, 1H, J = 4.7), 7.68 (d, 1H, J =
1.7), 7.60 (d, 1H, J = 3.3), 7.39 (m, 2H), 7.21 (m, 1H), 4.65 (m, 1H), 4.08 (s, 3H), 4.04 (m, 2H), 3.97 (s, 3H),
3.95 (s, 3H), 3.90 (s, 3H), 3.87 (s, 3H), 3.85 (s, 3H), 2.46 (s, 3H), 2.44 (s, 3H), 1.79 (m, 2H), 1.47 (s, 6H),
1.37 (m, 2H), 1.28 (m, 8H), 0.87 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 165.60, 163.26, 162.88, 162.74,
161.65, 156.28, 155.12, 149.29, 149.05, 145.10, 143.82, 140.94, 140.78, 136.78, 135.87, 135.52, 133.09,
132.90, 131.58, 129.24, 129.03, 128.91, 128.81, 128.69, 128.51, 128.34, 126.81, 126.69, 126.51, 128.33,
126.81, 126.70, 126.52, 126.12, 125.45, 124.72, 124.40, 123.25, 113.00, 112.20, 111.57, 110.83, 70.69, 68.59,
64.33, 63.16, 62.29, 52.11, 31.76, 29.62, 29.27, 29.18, 25.94, 22.60, 21.96, 21.33, 20.64, 14.04. HRMS-ESI:
calculated for [M]- (C54H62N52O15): m/z 1020.4242 found: m/z 1020.4203.
Compound 2g: 1t (4.00 g, 18.9 mmol) was reduced by catalytic hydrogenation in THF (100 mL) at 50 0C for
3 h. The resulting amine was dissolved in CH2Cl2 (100 mL) was immediately used for the next coupling. Acid
1m (6.00 g, 23.5 mmol) was dissolved in CH2Cl2 (150 mL) to which NMM (3.60 mL, 28.6 mmol) and ethyl
chloroformate (3.20 mL, 26.0 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
overnight at room temperature. The reaction mixture was washed with 1M KHSO4 (200 mL), followed by
saturated NaHCO3 (200 mL) and saturated NaCl (200 mL). Drying over Na2SO4 and removal of solvent in
vacuo gave the crude product, which was recrystallized from methanol to give the pure product 2g. Yield:
4.91 g, 62%. 1H NMR (300 MHz, CDCl3) δ 10.48 (s, 1H), 8.79 (d, 1H, J = 8.2), 7.93 (d, 1H, J = 3.2), 7.62 (d,
1H, J = 7.8), 7.47 (d, 1H, J = 3.2), 7.24 (m, 1H), 4.65 (m, 1H), 4.60 (s, 3H), 4.02 (s, 3H), 3.94 (s, 3H), 1.37 (s,
6H). 13C NMR (75 MHz, CDCl3) δ 165.80, 161.20, 153.98, 149.41, 144.47, 132.73, 129.59, 126.46, 124.51,
124.20, 123.50, 122.30, 116.13, 71.46, 64.51, 62.51, 52.28, 21.71. HRMS-ESI: calculated for [M+Na]+
(C20H22N2O8Na): m/z 440.1190 found: m/z 440.1194.
S14

Compound 3f: 2g (2.70 g, 6.45 mmol) was reduced by catalytic hydrogenation in THF (80 mL) at 50 0C for
3 h. The resulting amine dissolved in CH2Cl2 (80 mL) was immediately used for the next coupling. Acid 1l
(2.50 g, 7.69 mmol) was dissolved in CH2Cl2 (70 mL) to which NMM (1.24 mL, 10.1 mmol) and ethyl
chloroformate (1.00 mL, 8.45 mmol) was added at 0 0C. The reaction mixture was stirred for at least 15 min
then a solution of the above amine was added. The reaction mixture was allowed to stir continuously
0
overnight at 50 C. The reaction mixture was washed with 1M KHSO4 (60 mL), followed by saturated
NaHCO3 (60 mL) and saturated NaCl (60 mL). Drying over Na2SO4 and removal of solvent in vacuo gave the
1
crude product, which was recrystallized from methanol to give the pure product 3f. Yield: 3.70 g, 83%. H
NMR (300 MHz, CDCl3) δ 10.65 (s, 1H), 10.42 (s, 1H), 8.84 (d, 1H, J = 3.2), 8.50 (d, 1H, J = 3.2), 8.01 (d,
1H, J = 3.2), 7.61 (d, 1H, J = 8.0), 7.39 (d, 1H, J = 3.2), 7.23 (m, 1H), 7.11 (d, 1H, J = 2.9), 7.24 (m, 1H),
4.65 (m, 1H), 4.06 (s, 3H), 4.61 (m, 2H), 4.04 (m, 2H), 3.94 (s, 6H), 3.91 (s, 3H), 3.89 (s, 3H), 1.85 (m, 2H),
1.56 (s, 6H), 1.43 (m, 8H), 1.27 (m, 2H), 0.85 (m, 3H). 13C NMR (75 MHz, CDCl3) δ 165.91, 162.64, 161.24,
155.29, 155.02, 149.21, 144.62, 144.45, 140.93, 133.05, 132.64, 129.44, 126.70, 126.13, 124.52, 124.35,
123.43, 121.25, 115.12, 112.28, 112.53, 70.72, 69.29, 64.52, 63.33, 62.45, 52.32, 50.77, 31.73, 29.64, 29.18,
29.14, 28.87, 25.83, 22.59, 21.95, 14.08. HRMS-ESI: calculated for [M+Na]+ (C36H45N3O11Na): m/z 719.2846
found: m/z 719.2980.
Compound 3g: 3f (0.38 g, 0.54 mmol) was dissolved in hot methanol (10 mL) to which 1M KOH (1.37 mL,
1.37 mmol) and KCl (0.14 g, 1.82 mmol) was added. The mixture was heated under reflux for 2 h and then
quenched with water (20 mL). The aqueous layer was neutralized by addition of 1M HCl (2.0 mL) until the
pH was at least 1. The precipitated crude product was collected by filtration, which was recrystallized from
hot methanol to give a pure white solid 3g. Yield: 0.34 g, 93%. 1H NMR (500 MHz, CDCl3) δ 10.45 (s, 3H),
10.30 (s, 3H), 8.55 (d,1H, J = 7.6), 7.96 (d, 1H, J = 3.2), 7.65 (d, 1H, J = 3.2), 7.57 (d, 1H, J = 3.2), 7.50 (d,
1H, J = 7.6), 7.25 (d, 1H, J = 3.2), 7.22 (m, 1H), 4.61 (m, 1H), 4.08 (s, 3H), 4.07 (m, 2H), 4.01 (s, 3H), 3.85
(s, 6H), 4.03 (s, 3H), 1.73 (s, 6H), 1.41 (m, 2H), 1.31 (m, 8H), 1.28 (m, 2H), 0.84 (m, 3H). 13C NMR (75
MHz, DMSO-d6) δ 166.81, 162.94, 162.52, 154.26, 153.47, 149.22, 144.48, 143.27, 142.76, 132.52, 132.31,
127.38, 125.87, 125.23, 124.32, 123.80, 120.1, 114.36, 112.32, 112.08, 70.15, 68.85, 64.07, 62.86, 62.23,
31.25, 28.67, 28.39, 25.47, 22.10, 21.75, 13.95. HRMS-ESI: calculated for [M+Na]+ (C35H43N3O11Na): m/z
704.2790 found: m/z 704.2801.
Compound 6b: Compound 3a (0.20 g, 0.39 mmol) was reduced by catalytic hydrogenation in THF (15 mL)
0
at 50 C, using Pd-C (0.040 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the
solvent removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 3g
(0.30 g, 0.44 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-
prepared dry CH2Cl2 (5 mL) and DMF (27 μL) were added to the acid, followed by dropwise addition of
oxalyl chloride (67 μL, 0.53 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.17 g, 0.36 mmol) was dissolved in 10 mL dry CH2Cl2 and triethylamine (0.10 mL, 0.69 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (50 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
S15

(silica gel as the stationary phase) using CH2Cl2/CH3CN (20:1 v/v) as the eluent to give pure product 6b as a
1
white solid. Yield: 25 mg, 6%. H NMR (500 MHz, CDCl3) δ 10.20 (s, 2H), 10.12 (s, 1H), 10.09 (s, 1H),
10.08 (s, 1H), 9.82 (s, 1H), 8.65 (m, 2H), 8.61 (m, 2H), 8.26 (d, 1H, J = 3.2), 7.74 (m, 2H), 7.68 (d, 1H, J =
7.8), 7.62 (d, 1H, J = 3.2), 7.31 (d, 1H, J = 7.8), 7.21 (m, 3H), 7.16 (d, 1H, J = 3.2), 6.95 (t, 1H), 4.49 (m, 1H),
3.90 (s, 3H), 3.89 (s, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 3.78 (s, 3H), 3.63 (s, 3H), 3.61 (s, 3H), 1.66 (m, 2H),
1.46 (s, 6H), 1.29 (m, 8H), 1.13 (m, 2H), 0.63 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 165.22, 163.26,
162.83, 162.74, 161.11, 155.22, 155.14, 149.00, 147.26, 147.18, 147.02, 144.32, 144.04, 140.80, 133.09,
132.77, 132.41, 132.16, 129.32, 126.68, 126.58, 126.48, 126.38, 126.28, 126.06, 125.90, 125.86, 125.76,
125.26, 124.87, 124.78, 124.58, 124.25, 122.99, 121.34, 114.71, 112.83, 112.51, 70.73, 69.19, 64.45, 63.34,
63.00, 62.91, 62.13, 53.14, 50.70, 31.70, 29.61, 29.17, 29.11, 28.87, 25.84, 22.56, 21.91, 14.00. HRMS-ESI:
calculated for [M+Na]+ (C41H37N3O13Na): m/z 1165.4377 found: m/z 1165.4356.
Compound 5d: 4a (0.50 g, 0.734 mmol) was reduced by catalytic hydrogenation in THF (20 mL) at 50 0C,
using Pd-C (0.14 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1m (0.40
g, 1.56 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (10 mL) and DMF (0.10 mL) were added to the acid, followed by dropwise addition of oxalyl
chloride (0.20 mL, 1.60 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.48 g, 0.73 mmol) was dissolved in 10 mL dry CH2Cl2 and triethylamine (0.30 mL, 2.10 mmol) before
0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (40 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
(silica gel as the stationary phase) using hexane/ethyl acetate (2:1 v/v) as the eluent to give pure 5d as yellow
1
solid. Yield: 0.33 g, 52%. H NMR (500 MHz, CDCl3) δ 10.28 (s, 1H), 10.21 (s, 1H), 9.95 (s, 1H), 9.84 (s,
1H), 8.83 (d, 1H, J = 8.2), 8.79 (m, 3H), 7.92 (d, 1H, J = 3.1), 7.90 (m, 3H), 7.61 (d, 1H, J = 7.9), 7.49 (d,
1H, J = 3.1), 7.40 (m, 3H), 7.20 (m, 1H), 4.65 (m, 1H), 4.06 (s, 3H), 4.02 (s, 6H), 3.96 (s, 3H), 3.89 (s, 3H),
3.88 (s, 3H), 1.38 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 165.64, 163.17, 163.08, 162.88, 161.45, 154.19,
149.27, 147.29, 147.20, 144.65, 144.28, 133.04, 132.20, 132.02, 126.82, 126.66, 126.52, 126.39, 126.17,
125.87, 125.73, 125.09, 124.93, 124.84, 124.73, 124.44, 123.29, 122.36, 116.23, 71.54, 64.54, 63.21, 63.03,
62.36, 52.16, 29.65, 21.71 HRMS-ESI: calculated for [M+Na]+ (C44H43N5O14Na): m/z 888.2699 found: m/z
888.2723.
0
Compound 6c: 5d (0.10 g, 0.12 mmol) was reduced by catalytic hydrogenation in THF (5 mL) at 40 C,
using Pd-C (0.020 g, 20%) as the catalyst for 3 h. The reaction mixture was then filtered and the solvent
removed in vacuo to give the pure amine which was immediately used for the next coupling. Acid 1q (0.15 g,
0.71 mmol) was placed in a very dry round bottom flask and saturated with nitrogen gas. Freshly-prepared
dry CH2Cl2 (4 mL) and DMF (32 μL) were added to the acid, followed by dropwise addition of oxalyl
chloride (0.080 mL, 0.63 mmol). The reaction mixture was allowed to stir for 4 hrs. The solvent was then
removed in vacuo and saturated with nitrogen gas before addition of 10 mL dry CH2Cl2. The above amine
(0.090 g, 0.12 mmol) was dissolved in 5 mL dry CH2Cl2 and triethylamine (0.060 mL, 0.42 mmol) before
S16

0
addition to the reaction mixture above. The reaction mixture was stirred at 50 C for 6 hrs and then was
washed with aq NaHCO3 (10 mL). Drying over anhydrous Na2SO4 and removal of solvent in vacuo gave the
crude product which was recrystallised from methanol and further purified by flash column chromatography
(silica gel as the stationary phase) using hexane/ethyl acetate (1.5:1 v/v) as the eluent to give pure 6c as white
solid. Yield: 38 mg, 31%. 1H NMR (300 MHz, CDCl3) δ 10.28 (s, 1H), 10.25 (s,1H),10.15 (s, 1H), 10.14 (s,
1H), 9.85 (s, 1H), 8.83 (m, 2H), 8.81 (m, 2H), 8.46 (d, 1H, J = 3.2), 8.15 (d, 1H, J = 1.9), 7.94 (m, 3H), 7.68
(d, 1H, J = 1.9), 7.54 (d, 1H, J = 1.9), 7.52 (d, 1H, J = 1.9), 7.45 (m, 3H), 7.18 (m, 1H), 4.71 (m, 1H), 4.15 (s,
3H), 4,14 (s, 3H), 4.07 (s, 3H), 4.06 (s, 3H), 4.05 (s, 3H), 4.00 (s, 3H), 3.82 (s, 3H), 2.06 (s, 3H), 1.42 (s, 6H).
13C NMR (75 MHz, CDCl3) δ 165.26, 163.29, 162.87, 162.79, 161.40, 155.17, 149.04, 148.73, 147.19,
147.04, 143.69, 140.77, 136.74, 135.61, 133.13, 132.80, 132.42, 132.33, 132.16, 129.01, 128.36, 126.72,
126.62, 126.51, 126.43, 126.31, 126.07, 125.92, 125.81, 125.30, 124.89, 124.82, 124.61, 124.24, 123.06,
112.85, 112.44, 70.72, 64.33, 63.36, 63.04, 62.94, 62.19, 60.33, 52.18, 29.64, 21.94, 20.98, 20.64, 14.14.
HRMS-ESI: calculated for [M]- (C53H51N6O16): m/z 1027.3366 found: m/z 1027.3362.
Amide Hydrogen-Deuterim Exchange Experiments: Solutions of oligomers (5 mM) were
prepared by dissolving the compounds in 50% DMSO-d6 in CDCl3 (total volume: 0.95 mL) and the spectra
were recorded at room temperature as the reference spectra at t = 0. The H-D exchange experiment was
initiated by adding 0.05 mL of D2O into the samples, which resulted in a solution in a mixed solvent of
D2O/DMSO-d6/CDCl3 (2:19:19 v/v)). The resultant spectra were then recorded (500 MHz) at appropriate time
intervals, based on which the time dependent peak areas of the amide protons were obtained and fitted into
the pseudo-first-order reaction rate equation of (It - I)/(I0 - I∞) = e-kt, where It, I, and I0, correspond to the
integrated area of the corresponding proton at t = t, t = ∞, t = 0; k is the decayrate constant. The half-life T1/2
is related to k by T1/2 = ln2/k. Thus, the half-life T1/2 was obtained by fitting the time-dependent peak areas
into the above equation [(It - I∞)/(I0- I∞) = e-kt] with Origin 7.7 program.
S17

Table S1. Chemical shifts (ppm)a and the half-lives (hrs, in parenthesis) of H-D exchangeb of amide protons.
oligomer
2a
H6
H11
H16
H21
H26
10.36
(0.13)
10.37
(0.20)
2b
2c
10.47
(0.90)
10.25
(0.24)
2d
2e
10.49
(0.56)
10.24
(0.30)
8.70
(0.21)
2f
10.49
(0.83)
2g
10.21
(0.04)
10.23
(0.27)
3a
10.24
(0.05)
10.37
(0.24)
3b
3c
10.35
(0.08)
10.38
(1.34)
d)
10.36
(0.11)
10.38
(0.65)
3d
3e
10.35
(0.07)
10.36
(0.90)
10.33
(0.05)
10.35
(0.72)
3f
10.20
(0.63)
10.10
(0.03)
10.00
(0.06)
4a
10.33
(0.92)
10.14
(0.11)
10.10
(0.08)
4b
5a
10.25
(0.33)
9.85
(0.05)
9.85
(0.20)
10.25
(0.27)
c)
d)
10.35
(1.90)
9.85
(0.07)
9.65
(0.28)
10.25
(0.37)
5b
5c
10.35
(1.25)
10.10
(0.08)
9.85
(0.24)
10.10
(0.32)
10.28
(0.14)
10.21
(0.09)
9.95
(0.09)
9.84
(0.21)
5d
6a
10.19
(0.07)
10.12
(0.09)
9.84
(0.06)
10.28
(0.11)
10.15
(0.38)
10.12
(0.42)
10.08
(0.29)
9.81
(0.27)
10.21
(0.40)
10.09
(5.79)
6b
6c
10.28
(0.21)
10.25
(0.17)
10.15
(0.21)
10.15
(0.40)
9.85
(1.20)
a Chemical shifts were measured at 1 mM in CDCl3 (500MHz) at room temperature. b Half-lives of H-D exchange data in parenthesis
were measured at 5 mM in 5% D2O/47.5% DMSO-d6 (v:v) in CDCl3 at room temperature.
S18

Ab Initio Molecular Modelling: All the calculations were carried out by utilizing the Gaussian03
program package.1 The geometry optimizations were performed at the density functional theory (DFT) level,
and the Becke’s three parameter hybrid functional with the Lee-Yang-Parr correlation functional (B3LYP)2
method was employed to do the calculations. The 6-31G*3,4 basis from the Gaussian basis set library has been
used in all the calculations. All the trimers and hexamers were relaxed fully without any symmetry constraints.
The harmonic vibrational frequencies and zero-point energy corrections were calculated at the same level of
theory. Single point energy were obtained at the B3LYP level in conjunction with the 6-311+G(2d,p) basis
set with use of the above optimized geometries, i.e., B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d).
Determination of Crystal Structures: Data were collected on a Bruker APEX diffractometer with a
CCD detector and graphite-monochromated MoKα radiation using a sealed tube (2.4 kW) at 223(2) K.
Absorption corrections were made with the program SADABS5 and the crystallographic package SHELXTL6
was used for all calculations. In the final least-squares refinement cycles on |F|2, the model converged at R1 =
0.1335, wR2 = 0.1924, GoF = 1.081 for 6245 (I ≥ 2σ(I)) reflections.
1.
2.
3.
Frisch, M. J. In Gaussian 03, Gaussian , Inc.; Wallingford CT,, 2004.
Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
Petersson, G. A.; Bennett, A.; Tensfeldt, T. G.; Al-Laham, M. A.; Shirley, W. A.; Mantzaris, J. J.
Chem. Phys. 1988, 89, 2193.
4.
Petersson, G. A.; Al-Laham, M. A. J. Chem. Phys. 1991, 94, 6081.
Sheldrick, G. M.; SADABS Software for Empirical Absorption Corrections, University of GVttingen
(Germany), 2000.
5.
6.
SHELXTL Reference Manual, version 5.1, Bruker AXS, Analytical X-Ray Systems, Madison, WI, USA,
1997.
S19

X-Ray Crystal Data
Crystal data and structure refinement for 1c
Identification code
Empirical formula
Formula weight
Temperature
7098
C16 H24 O4
280.35
223(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 9.6816(6) Å
b = 11.8460(7) Å
c = 14.8820(9) Å
1531.93(16) Å3
4
α= 84.4210(10)°.
β= 75.4620(10)°.
γ = 68.0090(10)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.216 Mg/m3
0.086 mm-1
608
Crystal size
0.60 x 0.50 x 0.14 mm3
1.41 to 27.50°.
Theta range for data collection
Index ranges
-12<=h<=12, -15<=k<=15, -19<=l<=19
Reflections collected
Independent reflections
Completeness to theta = 27.50°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
19300
7021 [R(int) = 0.0305]
99.7 %
Sadabs, (Sheldrick 2001)
0.9881 and 0.9503
Full-matrix least-squares on F2
7021 / 0 / 367
1.031
R1 = 0.0552, wR2 = 0.1398
R1 = 0.0690, wR2 = 0.1486
0.349 and -0.220 e.Å-3
S20

Crystal data and structure refinement for 2a
Identification code
Empirical formula
Formula weight
Temperature
8008
C17 H16 N2 O7
360.32
223(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Monoclinic
P2(1)/c
Unit cell dimensions
a = 6.9923(4) Å
b = 28.3844(18) Å
c = 8.1995(5) Å
1626.94(17) Å3
4
α= 90°.
β= 91.323(2)°.
γ = 90°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.471 Mg/m3
0.116 mm-1
752
Crystal size
0.60 x 0.30 x 0.16 mm3
1.43 to 27.43°.
Theta range for data collection
Index ranges
-8<=h<=9, -36<=k<=36, -10<=l<=6
Reflections collected
Independent reflections
Completeness to theta = 27.43°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
11350
3708 [R(int) = 0.0252]
99.9 %
Sadabs, (Sheldrick 2001)
0.9817 and 0.9336
Full-matrix least-squares on F2
3708 / 0 / 242
1.065
R1 = 0.0491, wR2 = 0.1314
R1 = 0.0620, wR2 = 0.1391
0.337 and -0.211 e.Å-3
S21

Crystal data and structure refinement for 2b
Identification code
Empirical formula
Formula weight
Temperature
9177
C18 H18 N2 O8
390.34
223(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Monoclinic
P2(1)/c
Unit cell dimensions
a = 11.1282(4) Å
b = 25.3958(10) Å
c = 12.4272(5) Å
3503.9(2) Å3
8
α= 90°.
β= 93.9020(10)°.
γ = 90°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.480 Mg/m3
0.118 mm-1
1632
Crystal size
0.58 x 0.34 x 0.12 mm3
1.83 to 27.50°.
Theta range for data collection
Index ranges
-10<=h<=14, -32<=k<=32, -16<=l<=14
Reflections collected
Independent reflections
Completeness to theta = 27.50°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
24761
8027 [R(int) = 0.0234]
99.9 %
Semi-empirical from equivalents
0.9860 and 0.9346
Full-matrix least-squares on F2
8027 / 5 / 539
1.050
R1 = 0.0457, wR2 = 0.1235
R1 = 0.0548, wR2 = 0.1303
0.322 and -0.246 e.Å-3
S22

Crystal data and structure refinement for 2c
Identification code
Empirical formula
Formula weight
Temperature
9180
C25 H32 N2 O8
488.53
293(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 8.6807(5) Å
b = 12.2715(8) Å
c = 12.4359(8) Å
1249.75(14) Å3
2
α= 80.749(2)°.
β= 73.924(2)°.
γ = 81.848(2)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.298 Mg/m3
0.097 mm-1
520
Crystal size
0.50 x 0.20 x 0.14 mm3
1.69 to 27.50°.
Theta range for data collection
Index ranges
-11<=h<=10, -15<=k<=14, -16<=l<=12
Reflections collected
Independent reflections
Completeness to theta = 27.50°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
8919
5693 [R(int) = 0.0188]
99.3 %
Semi-empirical from equivalents
0.9865 and 0.9531
Full-matrix least-squares on F2
5693 / 8 / 346
1.047
R1 = 0.0535, wR2 = 0.1438
R1 = 0.0654, wR2 = 0.1525
0.317 and -0.194 e.Å-3
S23

Crystal data and structure refinement for 2d
Identification code
Empirical formula
Formula weight
Temperature
7172
C19 H20 N2 O9
420.37
223(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 7.4376(7) Å
b = 11.7525(11) Å
c = 12.3504(12) Å
955.90(16) Å3
2
α= 108.302(2)°.
β= 104.038(2)°.
γ = 100.220(2)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.460 Mg/m3
0.118 mm-1
440
Crystal size
0.54 x 0.28 x 0.12 mm3
1.83 to 27.49°.
Theta range for data collection
Index ranges
-9<=h<=9, -13<=k<=15, -16<=l<=13
Reflections collected
Independent reflections
Completeness to theta = 27.49°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
6786
4383 [R(int) = 0.0250]
99.4 %
Sadabs, (Sheldrick 2001)
0.9860 and 0.9392
Full-matrix least-squares on F2
4383 / 0 / 280
1.048
R1 = 0.0550, wR2 = 0.1344
R1 = 0.0808, wR2 = 0.1485
0.294 and -0.272 e.Å-3
S24

Crystal data and structure refinement for 3a
Identification code
Empirical formula
Formula weight
Temperature
8010
C25 H23 N3 O9
509.46
223(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Monoclinic
P2(1)/n
Unit cell dimensions
a = 7.0390(6) Å
b = 24.783(2) Å
c = 13.5449(12) Å
2325.1(3) Å3
4
α= 90°.
β= 100.260(2)°.
γ = 90°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.455 Mg/m3
0.112 mm-1
1064
Crystal size
0.56 x 0.46 x 0.14 mm3
1.64 to 27.43°.
Theta range for data collection
Index ranges
-8<=h<=9, -32<=k<=24, -17<=l<=17
Reflections collected
Independent reflections
Completeness to theta = 27.43°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
16262
5293 [R(int) = 0.0307]
99.8 %
Sadabs, (Sheldrick 2001)
0.9844 and 0.9397
Full-matrix least-squares on F2
5293 / 0 / 346
1.062
R1 = 0.0493, wR2 = 0.1259
R1 = 0.0671, wR2 = 0.1355
0.739 and -0.532 e.Å-3
S25

Crystal data and structure refinement for 3b
Identification code
Empirical formula
Formula weight
Temperature
8533
C27 H27 N3 O11
569.52
100(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 7.8202(4) Å
b = 11.1046(5) Å
c = 15.2948(7) Å
1251.77(10) Å3
2
α= 102.7860(10)°.
β= 93.9600(10)°.
γ = 103.0680(10)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.511 Mg/m3
0.119 mm-1
596
Crystal size
0.60 x 0.30 x 0.20 mm3
1.38 to 27.50°.
Theta range for data collection
Index ranges
-10<=h<=10, -14<=k<=14, -19<=l<=19
Reflections collected
Independent reflections
Completeness to theta = 27.50°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
16471
5736 [R(int) = 0.0256]
99.7 %
Sadabs, (Sheldrick 2001)
0.9766 and 0.9321
Full-matrix least-squares on F2
5736 / 0 / 384
1.038
R1 = 0.0429, wR2 = 0.1146
R1 = 0.0469, wR2 = 0.1176
0.427 and -0.209 e.Å-3
S26

Crystal data and structure refinement for 3c
Identification code
Empirical formula
Formula weight
Temperature
8534
C28 H29 N3 O12
599.54
295(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 7.6819(6) Å
b = 12.8663(9) Å
c = 15.3441(11) Å
1385.15(18) Å3
2
α= 70.1970(10)°.
β= 84.768(2)°.
γ = 76.122(2)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.437 Mg/m3
0.114 mm-1
628
Crystal size
0.70 x 0.36 x 0.20 mm3
1.41 to 27.50°.
Theta range for data collection
Index ranges
-9<=h<=9, -16<=k<=16, -19<=l<=19
Reflections collected
Independent reflections
Completeness to theta = 27.50°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
18159
6348 [R(int) = 0.0315]
99.9 %
Sadabs, (Sheldrick 2001)
0.9776 and 0.9245
Full-matrix least-squares on F2
6348 / 0 / 403
1.017
R1 = 0.0559, wR2 = 0.1378
R1 = 0.0765, wR2 = 0.1497
0.284 and -0.249 e.Å-3
S27

Crystal data and structure refinement for 3d
Identification code
Empirical formula
Formula weight
Temperature
7322
C35 H43 N3 O12
697.72
223(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 6.8316(8) Å
b = 15.8889(18) Å
c = 16.4300(18) Å
1737.1(3) Å3
2
α= 83.062(2)°.
β= 78.939(3)°.
γ = 87.588(2)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.334 Mg/m3
0.101 mm-1
740
Crystal size
0.60 x 0.10 x 0.06 mm3
1.70 to 25.00°.
Theta range for data collection
Index ranges
-8<=h<=8, -18<=k<=18, -19<=l<=19
Reflections collected
Independent reflections
Completeness to theta = 25.00°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
18541
6122 [R(int) = 0.0451]
100.0 %
Sadabs, (Sheldrick 2001)
0.9940 and 0.9418
Full-matrix least-squares on F2
6122 / 0 / 466
1.121
R1 = 0.0643, wR2 = 0.1517
R1 = 0.0840, wR2 = 0.1628
0.286 and -0.258 e.Å-3
S28

Crystal data and structure refinement for 4a
Identification code
Empirical formula
Formula weight
Temperature
7562
C33 H30 N4 O11
658.61
223(2) K
Wavelength
0.71073 Å
Triclinic
Crystal system
Space group
P-1
Unit cell dimensions
a = 8.0316(10) Å
b = 13.8306(17) Å
c = 15.0009(18) Å
1481.7(3) Å3
2
α= 109.279(2)°.
β= 93.852(2)°.
γ = 106.744(2)°.
Volume
Z
Density (calculated)
Absorption coefficient
F(000)
1.476 Mg/m3
0.113 mm-1
688
Crystal size
0.80 x 0.24 x 0.12 mm3
1.46 to 27.49°.
Theta range for data collection
Index ranges
-10<=h<=10, -17<=k<=17, -19<=l<=19
Reflections collected
Independent reflections
Completeness to theta = 27.49°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
10240
6769 [R(int) = 0.0303]
99.4 %
Sadabs, (Sheldrick 2001)
0.9866 and 0.9153
Full-matrix least-squares on F2
6769 / 0 / 450
1.002
R1 = 0.0616, wR2 = 0.1287
R1 = 0.1030, wR2 = 0.1457
0.497 and -0.298 e.Å-3
S29