714 J. B. BIALECKI ET AL.
(0.5 mL) and 15 mL of the solution was injected onto an
Aqua C18 RP column (150 ꢃ 4.60 mm i.d., 3-mm particle
size) from Phenomenex (Torrance, CA). The column was
eluted at a flow rate of 1 mL minꢀ1 with mobile phase A
(water with 0.1% HCOOH) to which mobile phase B
(acetonitrile with 0.1% HCOOH) was added by a linear
gradient (initially 2% B for 5 min, and then increased to
40% at 20 min, to 100% at 25 min, and then kept
isocratic for 5 min). The column was maintained at
ambient temperature and the ultraviolet (UV) detector
was set at 235 nm.
92%). dH (400 MHz; CDCl3) 7.88 (1H, s, PhCHNOH),
10.20 (1H, s, OH); dC (400 MHz; CDCl3) 132.0 (Ar–C1),
174.8 (PhCHNOH); m/z (EI) 126 (Mþꢁ, 100%), 124 (15),
109 (15), 83 (90), 82 (80), 71 (40), 52 (40), 42 (10),
40 (10).
[2,3,4,5,6-2H5]Phenylhydroxamic chloride ð3Þ
A solution of [2,3,4,5,6-2H5]benzaldehyde oxime (0.45 g,
3.6 mmol in 5 mL of DCM) and pyridine (0.1 mL) was
cooled to 08C in an ice bath, and N-chlorosuccinimide
(0.48g, 3.6 mmol) was slowly added. Upon completion,
the ice bath was removed and the reaction mixture was
stirred for 2 h at RT. The organic layer was separated and
washed with H2O (10 mL), dried over Na2SO4 and
evaporated to give the product (0.49g, 90%), which was
used in the next step without further purification. dC
(400 MHz; CDCl3) 137.0 (Ar–C1), 142.5 (C¼¼N); m/z (þve
ion electrospray) 142 ([M–HClþNH4]þ, 100%), 125 (10,
[M–HClþH]þ), 109 (20), 82 (30).
[2,3,4,5,6-2H5]Benzyl alcohol ð1Þ
[2,3,4,5,6-2H5]Benzoic acid (0.3 g, 2.4 mmol in 1.0 mL
of dry THF) was added to lithium aluminum deuteride
(0.144 g, 3.4 mmol in 1.0 mL of dry Et2O). The reaction
mixture was stirred at 408C for 16 h, cooled to 08C and
quenched with water (0.2 mL). The mixture was shaken
with 2 M HCl (10 mL) to dissolve the inorganic solids
and the aqueous layer was discarded. The organic layer
was dried over MgSO4 and evaporated to yield the
product as a clear liquid (205 mg, 83%). dH (400 MHz;
CDCl3) 2.52 (1H, s, OH), 4.62 (2H, s, CH2OH); dC
(400 MHz; CDCl3) 64.8 (PhCH2OH), 140.6 (Ar–C1); m/z
(EI) 113 (Mþꢁ, 100%), 112 (40), 96 (20), 84 (90), 83 (85),
81 (40), 68 (10), 54 (40), 42 (15).
S-20,30,40,60-tetra-O-acetyl-b-D-glucopyranosyl [2,3,4,
5,6-2H5]phenylthiohydroxamate ð4Þ
A solution of triethylamine (0.2 mL) and Et2O (1.0 mL)
was added to a stirred mixture of 1-thio-b-d-glucose
tetraacetate (0.4 g, 1.1 mmol) and [2,3,4,5,6-2H5]phe-
nylhydroxamic chloride (0.22 g, 1.4 mmol) in dry Et2O
(4.0 mL) and DCM (2.0 mL). A precipitate of triethyla-
mine hydrochloride formed immediately. The reaction
mixture was stirred for 2 h at RT. The mixture was then
washed with aq. HCl (10 mL, 1 M) and H2O (10 mL), and
the organic layer was separated, dried over Na2SO4 and
evaporated. The crude product was recrystallized from
ethanol to afford the pure white product (0.30 g, 60%).
dH (400 MHz; CDCl3) 2.03, 2.04, 2.09 and 2.12 (12H,
3 ꢃ s, OCOCH3), 3.04 (1H, s, H-4), 3.97 (1H, d,
J ¼ 12:4 Hz, H-3), 4.09 (1H, dd, J ¼ 12:4, 4.8 Hz, H-
2), 4.45 (1H, d, J ¼ 9:6 Hz, H-1), 5.01 (2H, d,
J ¼ 8:4 Hz, H-3), 5.08 (1H, td, J ¼ 7:2, 2.8 Hz, H-5),
8.90 (1H, s, PhCSNOH); dC (400 MHz; CDCl3) 20.5,
20.5, 20.6 and 20.7 (4 ꢃ OC(O)CH3), 61.8 (C-6), 67.8
(C-4), 69.8 (C-2), 73.7 (C-3), 75.7 (C-5), 81.4 (C-1),
132.3 (Ar–C1), 169.2, 169.2, 170.2 and 170.6,
(4 ꢃ OC(O)CH3); m/z (ꢀve ion electrospray) [M–H]ꢀ
C21H19D5NSO10 required 487.1435, found 487.1444.
[2,3,4,5,6-2H5]Benzaldehyde ð2Þ
A solution of [2,3,4,5,6-2H5]benzyl alcohol (1) (0.6 g,
5.4 mmol) in DCM (5 mL) was added to PCC (2.4 g,
11.2 mmol) in DCM (15 mL). The dark solution obtained
was stirred for 1 h at RT. The dark solids were filtered
from the reaction mixture and washed with DCM. The
filtrate obtained was washed with aq. NaOH (40 mL,
1 M) and HCl (20 mL, 1 M). The organic layer was
separated, dried over Na2SO4 and evaporated to yield
the final product as an oil (0.51 g, 84%). dH (400 MHz;
CDCl3) 9.92 (1H, s, PhCHO); dC (400 MHz; CDCl3)
136.8 (Ar–C1), 179.9 (PhCHO); m/z (EI) 111 (Mþꢁ,
100%), 110 (100), 83 (20), 82 (100), 54 (70), 52 (40),
42 (10), 40 (10).
[2,3,4,5,6-2H5]Benzaldehyde oxime
A solution of sodium carbonate (0.28 g, 2.6 mmol in
5 mL of H2O) was slowly added to a solution of
hydroxylamine hydrochloride (0.34 g, 4.8 mmol in
5 mL of H2O) and [2,3,4,5,6-2H5]benzaldehyde (0.50 g,
4.6 mmol), and the mixture was stirred at RT for 2 h.
The reaction mixture was extracted with Et2O (15 mL);
the Et2O layer was separated, dried over Na2SO4 and
evaporated to give the product as a colorless oil (0.52 g,
Pyridinium S-20,30,40,60-tetra-O-acetyl-b-D-glucopyr-
anosyl [2,3,4,5,6-2H5] phenylthiohydroxamic
N-sulfate ð5Þ
A stirred solution of the thiohydroxamate (4) (0.60 g,
1.24 mmol in 4.0 mL of DCM) and dry pyridine (5 mL)
was cooled to 08C in an ice bath and a cold solution of
Copyright # 2007 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2007; 50: 711–715
DOI: 10.1002.jlcr