Synthesis and characterization of linear and cyclic ... - EleA@UniSA

aldehyde 86 (0.72 g, 97%), as white solid; Rf (92/8 CH2Cl2/CH3OH) 0.56; crude 86 was used
immediately in the subsequent reductive amination reaction; H (300.10 MHz CDC13, mixture of
rotamers) 1.43 (4.05H, s, (CH3)3C), 1.45 (4.95H, s, (CH3)3C), 3.81 (0.9H, br s, CH2COO-tBu), 3.99 (2H,
br s, CH2CHO), and CH2COO-tBu, overlapped), 4.08 (1.1H, s, CH2CHO), 4.22-4.19 (1H, m, CH-
Fmoc), 4.42 (1.1H, d, J 6.0 Hz, CH2-Fmoc), 4.50 (0.9H, d, J 6.0 Hz, CH2-Fmoc), 7.29 (0.9H, br t, J 7.0
Hz, Ar. (Fmoc)), 7.38 (1.1H, t, J 7.0 Hz, Ar. (Fmoc)), 7.49 (0.9H, d, J 9.0 Hz, Ar. (Fmoc)), 7.56 (1.1H,
d, J 9.0 Hz, Ar. (Fmoc)), 7.73 (2H, m, Ar. (Fmoc)), 9.35 (0.45H, br s, CHO), 9.64 (0.55H, br s, CHO);
C (75.50 MHz, CDCl3) 28.2, 47.3, 50.6, 50.8, 57.8, 58.4, 68.1, 68.6, 82.6, 82.7, 120.2, 124.9, 125.2,
127.3, 128.0, 141.5, 143.8, 143.9, 156.0, 156.4, 168.6, 168.7, 198.7; m/z (ES) 396 (MH + ); (HRES) MH + ,
found 396.1809. C23H26NO5 + requires 396.1811.
(9H-fluoren-9-yl) methyl (tert-butoxycarbonyl) methyl 2-
((methoxycarbonyl)methylamino)ethylcarbamate (87):
To a solution of crude aldehyde 86 (0.72 g, 1.83 mmol) in dry CH2Cl2 (12 mL), a solution of glycine
methyl ester hydrochloride (0.30 g, 2.39 mmol) and Et3N (0.41 mL, 2.93 mmol) was added. The
reaction mixture was stirred for 1 h. Sodium triacetoxyborohydride (0.78 g, 3.66 mmol) was then added
and the reaction mixture was stirred overnight at room temperature. The resulting mixture was washed
with an aqueous saturated solution of NaHCO3 and the aqueous phase extracted with CH2Cl2 (three
times). The organic phase was dried over MgSO4, filtered and the solvent evaporated in vacuo to give
the crude product, which was purified by flash chromatography (AcOEt/petroleum ether/NH3 2.0M
solution in ethyl alcohol, from: 40/60/0.1 to 90/10/0.1) to give 87 (0.60 g, 70%) as a colorless oil;
[Found: C, 66.7; H, 6.9. C26H32N2O6 requires C, 66.65; H, 6.88%]; Rf (98/2/0.1, CH2Cl2/CH3OH/NH3
2.0M solution in ethyl alcohol) 0.63; H (400.13 MHz CDC13, mixture of rotamers) 1.45 (9H, s,
(CH3)3C), 2.56 (0.9H, t, J 6.0 Hz, N(Fmoc)CH2CH2NH), 2.83 (1.1H, t, J 6.0, N(Fmoc)CH2CH2NH),
3.27 (0.9H, t, J 6.0 Hz, N(Fmoc)CH2CH2NH), 3.29 (0.9H, s, CH2COOMe), 3.44 (1.1H, s,
CH2COOMe), 3.49 (1.1H, t, J 6.0 Hz, N(Fmoc)CH2CH2NH), 3.72 (3H, s, CH3), 3.91 (0.9H, s,
CH2COOtBu), 3.96 (1.1H, s, CH2COOtBu), 4.21 (0.45H, t, J 6.0 Hz, CH2CHFmoc), 4.26 (0.55H, t, J
6.0 Hz, CH2CHFmoc), 4.37 (1.1H, d, J 6.0 Hz, CH2CHFmoc), 4.51 (0.9H, d, J 6.0 Hz, CH2CHFmoc),
7.29 (2 H, t, J 7.0 Hz, Ar. (Fmoc)), 7.39 (2 H, t, J 7.0 Hz, Ar. (Fmoc)), 7.58 (2 H, m, Ar. (Fmoc)), 7.75
(2 H, d, J 7.0 Hz, Ar. (Fmoc)); C (100.03 MHz, CDCl3) 27.8, 47.0, 47.2, 47.4, 48.2, 48.6, 50.1, 50.3,
50.5, 53.3, 67.2, 67.6, 81.5, 81.7, 119.7, 124.7, 124.9, 126.8, 127.5, 141.0, 143.7, 156.0, 156.2, 168.7,
169.4, 171.9, 172.1; m/z (ES) 469 (MH + ); (HRES) MH + , found 469.2341. C26H33N2O6 + requires
469.2339.
Compound 88:
To a solution of 87 (0.60 g, 1.28 mmol) in DMF (30 mL), thymine-1-acetic acid (0.35 g, 1.90 mmol),
HATU (0.73 g, 1.90 mmol) and triethylamine (0.54 mL, 3.84 mmol) were added. The reaction mixture
was stirred overnight, concentrated in vacuo, dissolved in CH2Cl2 (20 mL) and washed 1M HCl
solution. The aqueous layer was extracted with CH2Cl2 (three times). The combined organic phases
were dried over MgSO4, filtered and the solvent evaporated in vacuo to give a crude material, which
was purified by flash chromatography (AcOEt/petroleum ether, from: 30/70 to 100/0) to give 88 (0.40 g,
49%) as yellow oil; [Found: C, 64.4; H, 6.2. C34H39N3O9 requires C, 64.44; H, 6.20%]; Rf (8/2,
41