A. Leitemberger, et al.
Bioorganic&MedicinalChemistry28(2020)115423
2H), 1.76–1.61 (m, 8H), 1.47–1.39 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ (ppm): 173.4, 163.9, 132.4, 130.0, 128.9, 126.7, 63.5, 61.9,
60.0, 55.3, 40.3, 33.8, 28.5, 28.2, 28.1, 27.1, 26.4, 24.6; HRMS (TOF
MS ESI+) m/z calcd for C20H28N2O3SSe [(M + H)+]: 457.1064; found:
457.1100.
2.95–2.85 (m, 3H), 2.71 (d, J = 12.8 Hz. 1H), 2.30 (t, J = 7.4 Hz. 2H),
1.74–1.62 (m, 8H), 1.45–1.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
(ppm): 173.5, 163.9, 136.2, 129.0, 128.7, 125.8, 63.6, 61.8, 60.0, 55.4,
40.4, 33.8, 33.1, 28.2, 28.1, 27.5, 25.4, 24.6; HRMS (TOF MS ESI+) m/
z calcd for C20H28N2O3S2 [(M + H)+]: 409.1620; found: 409.1638.
4.2.2.1.7. Synthesis of 5-(phenylseleno)pentyl 5-{(1R,5S,6S)-3-oxo-7-
thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5ba). Physical state: pasty
beige solid; Yield: 92%; 1H NMR (400 MHZ, CDCl3) δ (ppm):7.47–7.45
(m, 2H), 7.28–7.20 (m, 3H), 6.25 (s, 1H), 6.03 (s, 1H), 4.46–4.43 (m,
1H), 4.27–4.26 (m, 1H), 4.08–4.01 (m, 2H), 3.14–3.10 (m, 1H),
2.91–2.84 (m, 3H), 2.71 (d, J = 12.8 Hz. 1H), 2.33–2.28 (m, 2H),
1.72–1.61 (m, 8H), 1.51–1.44 (m, 4H); 13C NMR (100 MHz, CDCl3) δ
(ppm): 173.7, 164.2, 132.4, 130.5, 129.0, 126.7, 64.2, 62.1, 60.2, 55.5,
40.5, 33.9, 29.7, 28.4, 28.3, 28.1, 27.6, 26.1, 24.8; HRMS (TOF MS ESI
+) m/z calcd for C21H30N2O3SSe [(M + H)+]: 471.1221; found:
471.1207.
4.2.2.1.2. Synthesis
of
4-(4-methoxyphenylseleno)butyl
5-
{(1R,5S,6S)-3-oxo-7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate
(5ab). Physical state: pasty yellow solid; Yield: 82%; 1H NMR (400
MHZ, CDCl3) δ (ppm): 7.44 (d, J = 8.8 Hz. 2H), 6.80 (d, J = 8.8 Hz.
2H), 6.27 (s, 1H), 6.02 (s, 1H), 4.48–4.45 (m, 1H), 4.29–4.25 (m, 1H),
4.04 (t, J = 6.0 Hz. 2H), 3.78 (s, 3H), 3.15–3.10 (m, 1H), 2.86 (d,
J = 4.8 Hz. 1H), 2.81 (t, J = 6.8 Hz. 2H), 2.72 (d, J = 12.8 Hz. 1H),
2.29 (t, J = 7.68 Hz, 2H), 1.72–1.61 (m, 8H), 1.46–1.40 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ (ppm): 173.4, 163.9, 159.1, 135.4, 119.6,
114.6, 63.5, 61.8, 59.9, 55.3, 55.1, 40.3, 33.7, 28.4, 28.2, 28.1, 28.0,
26.4, 24.6; HRMS (TOF MS ESI+) m/z calcd for C21H30N2O4SSe
[(M + H)+]: 487.1170; found: 487.1202.
4.2.2.1.8. Synthesis
of
5-(4-methoxyphenylseleno)pentyl
5-
4.2.2.1.3. Synthesis of 4-(4-chlorophenylseleno)butyl 5-{(1R,5S,6S)-3-
oxo-7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5ac). Physical state:
pasty yellow solid; Yield: 73%; 1H NMR (400 MHZ, CDCl3) δ (ppm):
7.40 (d, J = 8.8 Hz. 2H), 7.22 (d, J = 8.8 Hz. 2H), 6.35 (s, 1H), 6.11 (s,
1H), 4.49–4.46 (m, 1H), 4.29–4.26 (m, 1H), 4.06–4.04 (m, 2H),
3.15–3.11 (m, 1H), 2.91–2.86 (m, 3H), 2.73 (d, J = 12.8 Hz. 1H),
2.30 (t, J = 7.6 Hz. 2H), 1.75–1.63 (m, 8H), 1.46–1.40 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ (ppm): 173.5, 163.9, 133.8, 132.8, 129.0,
128.2, 63.4, 61.8, 60.0, 55.4, 40.4, 33.8, 28.5, 28.2, 28.1, 27.5, 26.3,
24.6; HRMS (TOF MS ESI+) m/z calcd for C20H27ClN2O3SSe
[(M + H)+]: 491.0674; found: 491.0706.
{(1R,5S,6S)-3-oxo-7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate
(5bb). Physical state: pasty beige solid; Yield: 93%; 1H NMR (400 MHZ,
CDCl3) δ (ppm): 7.44 (d, J = 8.6 Hz. 2H), 6.80 (d, J = 8.6 Hz. 2H),
6.17 (s, 1H), 5.90 (s, 1H), 4.48–4.45 (m, 1H), 4.29–4.26 (m, 1H), 4.03
(t, J = 6.6 Hz. 2H), 3.78 (s, 3H), 3.16–3.12 (m, 1H), 2.90–2.86 (m, 1H),
2.80 (t, J = 7.4 Hz. 2H), 2.72 (d, J = 12.8 Hz. 1H), 2.30 (t, J = 7.4 Hz.
2H), 1.71–1.58 (m, 8H), 1.48–1.40 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ (ppm): 173.5, 163.9, 159.1, 135.3, 119.9, 114.6, 63.9, 61.9,
60.0, 55.3, 55.1, 40.3, 33.8, 29.6, 28.6, 28.2, 28.1, 27.9, 25.9, 24.6;
HRMS (TOF MS ESI+) m/z calcd for C22H32N2O4SSe [(M + H)+]:
501.1326; found: 501.1340.
4.2.2.1.4. Synthesis of 4-(4-toluylseleno)butyl 5-{(1R,5S,6S)-3-oxo-7-
thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5ad). Physical state: pasty
beige solid; Yield: 81%; 1H NMR (CDCl3, 400 MHz) δ = 7.38 (d.
J = 8 Hz. 2H), 7.07 (d, J = 8 Hz. 2H), 5.94 (s, 1H), 5.57 (s, 1H),
4.50–4.47 (m, 1H), 4.30–4.28 (m, 1H), 4.06–4.03 (m, 2H), 3.16–3.12
(m, 1H), 2.92–2.85 (m, 3H), 2.73 (d, J = 12.8 Hz. 1H), 2.31–2.28 (m,
5H), 1.74–1.65 (m, 8H), 1.46–1.41 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ (ppm): 173.6, 163.7, 136.9, 133.2, 129.8, 126.1, 63.7, 61.9,
60.1, 55.4, 40.5, 33.9, 28.6, 28.3, 28.2, 27.6, 26.6, 24.7, 21.0; HRMS
(TOF MS ESI+) m/z calcd for C21H30N2O3SSe [(M + H)+]: 471.1221;
found: 471.1225.
4.2.2.1.9. Synthesis of 5-(4-chlorophenylseleno)pentyl 5-{(1R,5S,6S)-
3-oxo-7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate
(5bc). Physical
state: pasty white sold; Yield: 80%; 1H NMR (400 MHZ, CDCl3) δ
(ppm): 7.40 (d, J = 8.4 Hz. 2H), 7.22 (d, J = 8.4 Hz. 2H), 5.67 (s, 1H),
5.32 (s, 1H), 4.51–4.47 (m, 1H), 4.31–4.28 (m, 1H), 4.04 (t, J = 6.6 Hz.
2H), 3.17–3.12 (m, 1H), 2.92–2.87 (m, 3H), 2.73 (d, J = 12.8 Hz. 1H),
2.31 (t, J = 7.4 Hz. 2H), 1.73–1.60 (m, 8H), 1.49–1.42 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ (ppm): 173.7, 163.5, 133.9, 132.9, 129.2,
128.5, 64.2, 61.9, 60.1, 55.4, 40.5, 33.9, 29.6, 28.3, 28.2, 28.1, 28.0,
26.1, 24.8; HRMS (TOF MS ESI+) m/z calcd for C21H29ClN2O3SSe
[(M + H)+]: 505.0831; found: 505.0861.
Synthesis of 4-(butylselanyll)butyl 5-{(1R,5S,6S)-3-oxo-7-thia-2.4-
diazabicyclo[3.3.0]oct-6-yl}valerate (5ae): Physical state: pasty white
solid; Yield: 78%; 1H NMR (400 MHZ, CDCl3) δ (ppm): 6.36–6.34 (m,
1H), 6.12–6.09 (m, 1H), 4.51–4.48 (m, 1H), 4.31–4.28 (m, 1H),
4.07–4.06 (m, 2H), 3.17–3.13 (m, 1H), 2.92–2.87 (m, 1H), 2.74 (d,
J = 12.8 Hz. 1H), 2.58–2.54 (m, 4H), 2.32 (t, J = 7.4 Hz. 2H),
1.73–1.60 (m, 10H), 1.47–1.37 (m, 4H), 0.91 (t, J = 7.4 Hz. 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm): 173.5, 163.9, 63.6, 61.8, 59.9, 55.3,
40.3, 33.7, 32.5, 28.6, 28.2, 28.0, 26.8, 24.6, 23.5, 23.0, 22.8, 13.4;
HRMS (TOF MS ESI+) m/z calcd for C18H32N2O3SSe [(M + H)+]:
437.1377; found: 437.1405.
4.2.2.1.10. Synthesis of 5-(4-toluylseleno)pentyl 5-{(1R,5S,6S)-3-oxo-
7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5bd). Physical state:
pasty white solid; Yield: 92%; 1H NMR (400 MHZ, CDCl3) δ (ppm):
7.38 (d, J = 8.2 Hz. 2H), 7.06 (d, J = 8.2 Hz. 2H), 4.52–4.49 (m, 1H),
4.33–4.30 (m, 1H), 4.04 (t, J = 6.6 Hz. 2H), 3.18–3.13 (m, 1H),
2.93–2.84 (m, 3H), 2.74 (d, J = 12.8 Hz.1H), 2.33–2.29 (m, 5H),
1.73–1.60 (m, 8H), 1.49–1.42 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ
(ppm): 173.6, 163.4, 136.8, 133.1, 129.8, 126.4, 64.3, 62.1, 60.3, 55.3,
40.5, 33.9, 29.8, 28.4, 28.3, 28.1, 28.0, 26.1, 24.8, 21.0; HRMS (TOF
MS ESI+) m/z calcd for C22H32N2O3SSe [(M + Na)+]: 507.1197;
found: 507.1205.
4.2.2.1.5. Synthesis of 4-(phenyltelluro)butyl 5-{(1R,5S,6S)-3-oxo-7-
thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5af). Physical state: pasty
yellow solid; Yield: 66%; 1H NMR (400 MHZ, CDCl3) δ (ppm):
7.73–7.70 (m, 2H), 7.30–7.17 (m, 3H), 5.83 (sl. 1H), 5.47 (sl. 1H),
4.50–4.47 (m, 1H), 4.31–4.27 (m, 1H), 4.05 (t, J = 6.4 Hz. 2H),
3.17–3.12 (m, 1H), 2.92–2.88 (m, 3H), 2.73 (d, J = 12.8 Hz. 1H), 2.29
(t, J = 7.4 Hz. 2H), 1.87–1.62 (m, 8H), 1.47–1.38 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm): 173.6, 163.6, 138.4, 129.2, 127.6, 111.5,
63.5, 61.9, 60.1, 55.4, 40.5, 33.9, 30.8, 28.3, 28.2, 24.8, 7.7; HRMS
(TOF MS ESI+) m/z calcd for C20H28N2O3STe [(M + H)+]: 507.0961;
found 507.0995.
4.2.2.1.11. Synthesis of 5-(butylselanyll)pentyl 5-{(1R,5S,6S)-3-oxo-
7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5be). Physical state:
pasty white solid; Yield: 78%; 1H NMR (400 MHZ, CDCl3) δ (ppm):
6.22 (s, 1H), 5,90 (sl. 1H), 4.51–4.48 (m, 1H), 4.32–4.29 (m, 1H), 4.06
(t, J = 6.8 Hz. 2H), 3.18–3.13 (m, 1H), 2.90 (dd, J1 = 12.6 Hz.
J2 = 5.0 Hz. 1H), 2.74 (d, J = 12.8 Hz. 1H), 2.55 (t, J = 7.4 Hz. 4H),
2.33 (t, J = 7.4 Hz. 2H), 1.72–1.60 (m, 10H), 1.48–1.37 (m, 6H), 0.91
(t, J = 7.4 Hz. 3H); 13C NMR (100 MHz, CDCl3) δ (ppm): 173.6, 163.9,
64.1, 61.9, 60.1, 55.4, 40.4, 33.8, 32.6, 30.1, 28.3, 28.1, 28.0, 26.2,
24.7, 23.6, 23.5, 22.9, 13.5; HRMS (TOF MS ESI+) m/z calcd for
C
19H34N2O3SSe [(M + H)+]: 451.1534; found: 451.1518.
4.2.2.1.6. Synthesis of 4-(phenylthio)butyl 5-{(1R,5S,6S)-3-oxo-7-
thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5ag). Physical state: pasty
white solid; Yield: 76%; 1H NMR (400 MHZ, CDCl3) δ (ppm): 7.32–7.25
(m, 4H), 7.18–7.14 (m, 1H), 6.27 (s, 1H), 5.99 (s, 1H), 4.47–4.44 (m,
1H), 4.28–4.25 (m, 1H), 4.06 (t, J = 6.2 Hz. 2H), 3.15–3.10 (m, 1H),
4.2.2.1.12. Synthesis of 5-(phenyltelluro)pentyl 5-{(1R,5S,6S)-3-oxo-
7-thia-2.4-diazabicyclo[3.3.0]oct-6-yl}valerate (5bf). Physical state:
pasty yellow solid; Yield: 68%; 1H NMR (400 MHZ, CDCl3) δ (ppm):
7.70–7.68 (m, 2H), 7.30–7.16 (m, 3H), 6.28 (s, 1H), 6.04 (s, 1H),
4.47–4.43 (m, 1H), 4.28–4.25 (m, 1H), 4.02 (t, J = 6.6 Hz. 2H),
8