Synthesis of 2-Carboxy-6-hydroxyoctahydroindole (Choi) Core Unit for the Synthesis of Aeruginosins

Abstract

The synthesis of N,O-protected 2-carboxy-6-hydroxyoctahydroindole (Choi) core unit for the synthesis of aeruginosins has been described.

Key words

2-carboxy-6-hydroxyoctahydroindole - choi - aeruginosin - trypsin - thrombin

References

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4

Toyooka, N.; Nakazawa, A.; Himiyama, T.; Nemoto, H. Heterocycles 2003, 59, in press.

10

Data of the GMMX and MOPAC calculations for 10′ and 12′ are shown in Figure [3] .

Figure 3

11

The stereochemistry at the 6-position of 13 and 14 was determined by the chemical shifts and coupling constants in the ¹H NMR spectra as shown in Figure [4] .

Figure 4

12

The spectral data for synthetic 1 are as follows. ¹H NMR (500 MHz, CDCl₃): δ = 1.40 and 1.46 (9 H, each s), 1.51 (1 H, br), 1.61 (1 H, br), 1.69 (1 H, br t, J = 11.5 Hz), 1.96 (2 H, br), 2.12-2.18 (2 H, m), 2.36 (1 H, br), 3.74 (3 H, s), 4.15 (1 H, br s), 4.22 (1 H, br), 4.29 (1 H, br). ¹³C NMR (125 MHz, CDCl₃): δ = 19.46 (CH₂), 26.29 and 26.60 (each CH₂, due to rotamers), 28.25 and 28.42 (each CH₃, due to rotamers), 31.61 and 32.44 (each CH₂, due to rotamers), 33.64 and 33.78 (each CH₂, due to rotamers), 35.83 and 36.42 (each CH, due to rotamers), 51.95 and 52.13 (each CH₃, due to rotamers), 53.45 and 53.69 (each CH, due to rotamers), 58.87 and 59.38 (each CH, due to rotamers), 65.92 and 66.18 (each CH, due to rotamers), 79.86 (C), 153.24 (C), 174.01 and 174.11 (each C, due to rotamers). ¹H NMR (500 MHz, DMSO-d ₆, 80 °C): δ = 1.36 (9 H, s), 1.43 (2 H, m), 1.51 (1 H, m), 1.85 (1 H, q-like, J = 9.9 Hz), 2.01 (2 H, m), 2.11 (1 H, dt, J = 12, 7.3 Hz), 2.26 (1 H, m), 3.65 (3 H, s), 3.89 (1 H, br), 4.01 (1 H, m), 4.16 (1 H, m). ¹³C NMR (100 MHz, DMSO-d ₆, 80 °C): δ = 19.16 (CH₂), 26.39 (CH₂), 27.70 (CH₃), 31.42 (CH₂), 33.20 (CH₂), 35.30 (CH), 51.13 (CH₃), 53.39 (CH), 58.54 (CH), 63.74 (CH), 78.25 (C), 161.61 (C), 172.93 (C). Lit. [3a] [b] [α]_D -31.1 (c 2.4, MeOH); [α]_D ²⁶ -36.2 (c 1.25, MeOH).