Beilstein J. Org. Chem. 2014, 10, 2539–2549.
organic phase was washed with saturated aq NaHCO3 solution 66.20 (CH2Oisomer 2), 169.8 (NC=Oisomer 1), 169.9
and brine. Drying with MgSO4, filtration and evaporation of the (NC=Oisomer 2), 174.9 (OC=Oisomer 1), 175.0 (OC=Oisomer 2);
solvent gave the corresponding acylated homoserine lactones 6 MS (ESI) m/z (%): 278/280 (M + H+, 100); HRMS calcd for
and 8. The crude product was purified via column chromatog- C10H16BrNO3H+, 278.0386; found, 278.0378; IR (cm−1) νmax:
raphy on silica gel (EtOAc/petroleum ether 4:1).
1008, 1178 (C-O), 1554 (HN-C=O), 1655 (HN-C=O), 1769
(C=Olactone), 2860 (CH), 2924 (CH), 2957 (CH), 3298 (NH);
chromatography: EtOAc/PE 4:1 Rf 0.48; melting point: 148 °C;
white powder; yield: 54%.
Synthesis of α-chloro acylated homoserine lactones
11a–f
In a flask containing the appropriate acid chloride 2 (5 mmol)
which was kept under a nitrogen atmosphere at 0 °C, P(OMe)3 2-Iodo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]hexan-
(1.16 equiv, 1.45 mL, 5.8 mmol) was added. The mixture was amide) (8a)
stirred for 4 h at room temperature. Then the excess of P(OMe)3 1H NMR (300 MHz, CDCl3) δ 0.91 (t, J = 7.2 Hz, 3H,
and MeCl were evaporated under reduced pressure. The flask CH3, isomer 1 and 2), 1.21–1.50 (m, 4H, (CH2)2CH3, isomer 1 and 2),
was covered with aluminium foil and SO2Cl2 (1.3 equiv, 1.99 (q, J =7.2 Hz, 2H, CH2CHIisomer 1 and 2), 2.11–2.29 (m,
0.52 mL, 6.5 mmol) was added via a syringe at 0 °C. After stir- 1H, OCH2CHH'isomer
ring for 14 h at room temperature, the reaction was quenched by OCH2 CHH'i s o m e r
1
and 2), 2.82–2.94 (m, 1H,
1
a n d 2 ), 4. 26–4. 36 (m, 1H,
adding 5 mL of dry CH2Cl2 and bubbling nitrogen through the OCHH'isomer 1 and 2), 4.30 (t, J = 7.2 Hz, 1H, CHIisomer 1 and 2),
solution to remove excess of SO2Cl2 and HCl. The chlorinated 4.46–4.53 (m, 0.5H, CHNisomer 1), 4.51 (t, J = 8.8 Hz, 1H,
acylphosphonates 10 were added at 0 °C to a bulb containing OCHH'isomer 1 and 2), 4.60 (ddd, J = 11.8 Hz, 8.5 Hz, 6.1 Hz,
(S)-homoserine lactone 1 (1.3 equiv, 1.18 g, 6.5 mmol) and 0.5H, CHNisomer 2), 6.43 (d, J = 6.1 Hz, 0.5H, NHisomer 1), 6.52
Et3N (2.6 equiv, 1.8 mL, 13 mmol) in 10 mL of dry CH2Cl2. (d, J = 6.1 Hz, 0.5H, NHisomer 2); 13C NMR (75 MHz, CDCl3)
This reaction mixture was stirred for 4 h at room temperature
δ
13. 9 (CH3 , i s o m e r
1 a n d 2 ), 22. 0 and 31. 6
under nitrogen. Then the mixture was poured into 20 mL ((CH2)2CH3, isomer 1 and 2), 24.9 (CHIisomer 1 and 2), 29.6
0.1 M aq HCl and extracted with 20 mL of CH2Cl2. The (CH2CHNisomer 1), 29.7 (CH2CHNisomer 2), 36.2
organic phase was dried with MgSO4, filtered to remove the (CH2CHIisomer 1), 36.3 (CH2CHIisomer 2), 49.6 (CHNisomer 1),
MgSO4 and the solvent was removed under reduced pressure. 49.8 (CHNisomer 2), 66.3 (CH2Oisomer
1 and 2), 171.4
The crude product was purified by column chromatography on (NC=Oisomer 1 ), 171.5 (NC=Oisomer 2), 175.3 (OC=Oisomer 1),
silica gel (EtOAc/petroleum ether 4:1) to give the desired prod- 175.4 (OC=Oisomer 2); MS (ESI) m/z (%): 326 (M + H+, 100);
uct.
HRMS calcd for C10H16INO3H+, 326.0253; found, 326.0244;
IR (cm−1) νmax: 1016, 1176 (C-O), 1546 (HN-C=O), 1642 (HN-
C=O), 1770 (C=Olactone), 2858 (CH), 2929 (CH), 2956 (CH),
Characterization of novel compounds
Representative characterization data for novel analogues. Char- 3296 (NH); chromatography: EtOAc/PE 4:1 Rf 0.62; melting
acterization of all compounds can be found in the Supporting point: 152 °C; yellowish powder; yield: 49%.
2-Chloro-N-[(3S)-tetrahydro-2-oxo-3-furanyl]hexan-
2-Bromo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]hexan-
amide) (6a)
amide) (11a)
1H NMR (300 MHz, CDCl3) δ 0.92 (t, J = 7.2 Hz, 3H,
1H NMR (300 MHz, CDCl3) δ 0.92 (t, J = 7.0 Hz, 3H, CH3, isomer 1 and 2), 1.26–1.55 (m, 4H, (CH2)2CH3isomer 1 and 2),
CH3isomer 1 and 2), 1.30–1.53 (m, 4H, (CH2)2CH3isomer 1 and 2), 1.87–2.01 (m, 1H, CHH'CHClisomer 1 and 2), 2.05–2.18 (m, 1H,
1.94–2.07 (m, 1H, CHH'CHBrisomer 1 and 2), 2.08–2.16 (m, 1H, CHH'CHClisomer 1 and 2), 2.26 (dddd, J = 11.8 Hz, 11.8 Hz, 11.7
CHH'CHBri s o m e r
OCH2 CHH'i s o m e r
1
a n d 2 ), 2. 16–2. 30 (m, 1H, Hz, 8.8 Hz, 1H, OCH2CHH'isomer 1 and 2), 2.74–2.84 (m, 1H,
a n d 2 ) , 2. 79–2. 90 (m, 1H, OCH2CHH’isomer 1 and 2), 4.27–4.40 (m, 2H, CHClisomer 1 and 2
1
OCH2CHH'isomer 1 and 2), 4.22–4.36 (m, 2H, CHBrisomer 1 and 2 and OCHH'isomer
1 and 2), 4.50 (t, J = 8.8 Hz, 1H,
and OCHH'isomer and 2), 4.50 (t, J = 9.1 Hz, 1H, OCHH'isomer 1 and 2), 4.55–4.64 (m, 1H, CHNisomer 1 and 2), 7.22
1
OCHH'isomer 1 and 2), 4.52–4.61 (m, 1H, CHNisomer 1 and 2), 7.01 (d, J = 6.1 Hz, 0.5H, NHisomer 1), 7.25 (d, J = 6.1 Hz, 0.5H,
(d, J = 5.5 Hz, 1H, NH,isomer 1 and 2); 13C NMR (75 MHz, NHisomer 2); 13C NMR (75 MHz, CDCl3) δ 13.9
CDCl3) δ 13.9 (CH3isomer 1 and 2), 22.0 (CH2CH3isomer 1 and 2), (CH3, isomer 1 and 2), 22.0 (CH2CH3, isomer 1 and 2), 27.9
29.35 (CH2CH2CHBrisomer 1), 29.39 (CH2CH2CHBrisomer 2), (CH2CH2CHClisomer 1), 28.0 (CH2CH2CHClisomer 2), 29.7
29.9 (CH2CHNisomer 1 and 2), 35.36 (CH2CHBrisomer 1), 35.41 (CH2CHNisomer 1 and 2), 35.2 (CH2CHClisomer 1 and 2), 49.4
(CH2CHBrisomer 2), 49.8 (CHNisomer
1 and 2), 50.3 (CHNisomer 1), 49.5 (CHNisomer 2), 60.47 (CHClisomer 1), 60.50
(CHBrisomer 1), 50.4 (CHBrisomer 2), 66.17 (CH2Oisomer 1), (CHClisomer 2), 66.07 (CH2Oisomer 1), 66.12 (CH2Oisomer 2),
2547