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34.2, 31.8 ppm. FTIR (thin film): n˜ =1860, 1792 cmÀ1 ESI-MS m/z=
319.0063 [MÀH]À (calcd 319.0059 for C10H11N2O6S2).
l-Lanthionine[12]
TFA-l-lanthionine-OMe (1.0 g, 2.3 mmol, 1.0 equiv), was dissolved
in THF (12 mL) and cooled to 08C. 2n NaOH (25 mL) was added
dropwise and the reaction was allowed to stir for 1 h at 08C. 1n
HCl (12 mL) was added and the mixture was adjusted to pH 6 with
1n HCl. The solvent was removed in vacuo. The residue was sus-
pended in water and filtered to give l-lanthionine as white crystals
(0.27 g, 55% yield). 1H NMR (400 MHz, TFA-D, 258C): d=4.69 (s,
2H), 3.63–3.53 (m, 2H), 3.5–3.4 ppm (m, 2H). 13C NMR (100 MHz,
TFA-D, 258C): d=170.3, 53.0, 31.2 ppm.
l-Lanthionine di-NCA (1c)
l-Lanthionine (0.27 g, 1.3 mmol, 1.0 equiv) was suspended in THF
(30 mL). 15% phosgene solution in toluene (3.6 mL, 5.1 mmol,
4 equiv) was added. The mixture was stirred at 458C for 18 h and
then concentrated. The crude product was purified by column
chromatography (60:40 THF:hexanes) under inert atmosphere.
After concentration, the material was diluted with THF and precipi-
tated into hexanes. This provided the product as a white solid
l-Homolanthionine[21]
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(0.20 g, 59% yield). H NMR (400 MHz, CD3CN, 258C): d=6.84 (br s,
2H), 4.62–4.58 (m, 2H), 3.12–3.07 (dd, J=4.0, 14.5 Hz, 2H), 3.01–
2.95 ppm (m, 2H). 13C NMR (100 MHz, CD3CN, 258C): d=169.51,
151.67, 58.4, 34.0 ppm. FTIR (thin film): n˜ =1860, 1790 cmÀ1. ESI-MS
m/z=259.0031 [MÀH]À (calcd 259.0025 for C8H7N2O6S).
TFA-l-homolanthionine-OMe (0.56 g, 1.2 mmol, 1.0 equiv), was dis-
solved in THF (8 mL) and cooled to 08C. 2n NaOH (12 mL) was
added dropwise and the reaction was allowed to stir for 1 h at
08C. 1n HCl (6 mL) was added and the mixture was adjusted to
pH 6 with 1n HCl. The solvent was removed in vacuo. The residue
was dissolved in water (5 mL) and precipitated into absolute etha-
nol (45 mL) and placed in the freezer overnight. The reaction was
centrifuged and the supernatent was removed. Excess ethanol was
removed under high vacuum to yield white crystals (0.24 g, 81%
l-Cystathionine di-NCA (1d)
l-Cystathionine (0.30 g, 1.3 mmol, 1.0 equiv) was suspended in THF
(20 mL). 15% phosgene solution (3.9 mL, 5.4 mmol, 4 equiv) was
added. The mixture was stirred at 458C for 18 h and then concen-
trated. The crude product was purified by column chromatography
(60:40 THF:hexanes) under inert atmosphere. After concentration,
the material was diluted with THF and precipitated into hexanes.
This provided a colorless solid (0.20 g, 54% yield). 1H NMR (400 MHz,
CD3CN, 258C): d=6.86 (br m, 2H), 4.62 (dd, J=4.2, 1.3 Hz, 1H), 4.44
(dd, J=1.4, 5.6 Hz, 1H), 3.04 (dd, J=14.5, 4.0 Hz, 1H), 2.92 (dd, J=
14.5, 5.2 Hz, 1H), 2.71 (t, J=7.4 Hz, 2H), 2.06 ppm (m, 2H). 13C NMR
(100 MHz, CD3CN, 258C): d=170.9, 169.7, 151.8, 151.8, 58.2, 56.1,
32.4, 30.8, 28.0 ppm. FTIR (thin film): n˜ =1860, 1792 cmÀ1. ESI-MS
m/z=273.0204 [MÀH]À (calcd 273.0181 for C9H9N2O6S2).
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yield). H NMR (400 MHz, TFA-D, 258C): d=4.70 (q, J=6.0 Hz, 2H),
3.00 (t, J=6.7 Hz, 2H), 2.67–2.45 ppm (m, 4H). 13C NMR (100 MHz,
TFA-D, 258C): d=172.7, 53.0, 28.3, 26.8 ppm.
l-Cystathionine[11]
l-Homocysteine thiolactone-HCl (0.60 g, 3.9 mmol, 1.0 equiv) and
3-chloro-l-alanine (0.63 g, 5.1 mmol, 1.3 equiv) were added to a
flask and flushed with N2. Degassed 5 N NaOH (3.5 mL, 18 mmol,
4.5 equiv) was added. The mixture was stirred for 64 h. The pH was
adjusted to 10.5–11.0 with conc. HCl(aq). The mixture was cooled to
48C and allowed to stand for 16 h. The precipitate was collected
by vacuum filtration. The amino acid was recovered as a colorless
l-Homolanthionine di-NCA (1e)
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solid (470 mg, 54% yield). H NMR (400 MHz, D2O, 258C): d=4.30
l-Homolanthionine (0.23 g, 1.0 mmol, 1.0 equiv) was suspended in
THF (30 mL). A solution of 15% phosgene in toluene (2.8 mL,
4.0 mmol, 4 equiv) was added. The mixture was stirred at 458C for
24 h. The turbid mixture was concentrated and the crude product
was purified by column chromatography (60:40 THF:hexanes) under
inert atmosphere. After concentration, the material was diluted with
THF and precipitated into hexanes. This provided a sticky white
(dd, J=7.3, 4.5 Hz, 1H), 4.20 (t, J=6.5 Hz, 1H), 3.25 (dd, J=15.2,
4.6 Hz, 1H), 3.15 (dd, J=15.1, 7.2 Hz, 1H), 2.80 (tm, J=7.6 Hz, 2H),
2.30 (m, 1H), 2.21 ppm (m, 1H).
l-Cystine di-NCA (1a)
l-Cystine (1.5 g, 6.2 mmol, 1.0 equiv) was suspended in THF
(50 mL). Triphosgene (2.5 g, 8.3 mmol, 1.3 equiv) was added in one
portion. The mixture was stirred at 508C for 24 h. The turbid mix-
ture was concentrated and the crude product was purified by
column chromatography (50:50 THF:hexanes) under inert atmos-
phere. After concentration, the material was diluted with THF and
precipitated into hexanes. This provided a pale yellow solid (0.42 g,
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solid (0.03 g, 12% yield). H NMR (400 MHz, CD3CN, 258C): d=6.87
(br s, 2H), 4.47 (ddd, J=6.9, 5.4, 1.3 Hz, 2H), 2.80 (t, J=7.2 Hz, 4H),
2.19 ppm (m, 4H). 13C NMR (100 MHz, CD3CN, 258C): d=171.0,
151.8, 56.2, 30.5, 26.3 ppm. FTIR (thin film): n˜ =1856, 1788 cmÀ1
ESI-MS m/z=287.0337 [MÀH]À (calcd 287.0338 for C10H11N2O6S).
.
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23% yield). The IR and H NMR for this material were in accordance
g-tertButyl l-glutamate NCA (Bu-Glu NCA)
with those previously reported.[8–10]
g-tertButyl l-glutamic acid (2.0 g, 9.8 mmol, 1.0 equiv) was sus-
pended in THF (60 mL). Triethylamine (2.75 mL, 19.7 mmol,
2.0 equiv) and TMSCl (2.5 mL, 19.7 mmol, 2.0 equiv) were added
and the turbid mixture was stirred for 1 h at room temperature.
Phosgene (15% in toluene) (10.2 mL, 14.7 mmol, 1.5 equiv) was
added and the mixture was heated to 458C and allowed to react
for 2 h. The turbid mixture was concentrated, filtered, and the
crude product was purified by column chromatography (30:70
THF:Hexanes to 50:50 THF:Hexanes) under inert atmosphere. After
concentration, the material was crystallized twice from 3:1
Hex:THF to provide a white fluffy solid (1.75 g, 68%). The IR and
1H NMR for this material were in accordance with those previously
reported.[14]
l-Homocystine di-NCA (1b)
l-Homocystine (0.4 g, 1.5 mmol, 1.0 equiv) was suspended in THF
(30 mL). Triphosgene (0.59 g, 2.0 mmol, 1.3 equiv) was added in
one portion. The mixture was stirred at 508C for 24 h. The turbid
mixture was concentrated and the crude product was purified by
column chromatography (60:40 THF:hexanes) under inert atmos-
phere. After concentration, the material was diluted with THF and
precipitated into hexanes. This provided a colorless solid (0.20 g,
42% yield). 1H NMR (400 MHz, CD3CN, 258C): d=6.87 (br s, 2H),
4.47 (ddd, J=6.9, 5.4, 1.3 Hz, 2H), 2.80 (t, J=7.2 Hz, 4H), 2.19 ppm
(m, 4H). 13C NMR (100 MHz, CD3CN, 258C): d=172.1, 153.2, 57.5,
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Chem. Asian J. 2018, 00, 0 – 0
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