S. Stadlbauer, P. Lönnecke, P. Welzel, E. Hey-Hawkins
FULL PAPER
toSIL® phase (gradient CH3CN/H2O, 80:20 over 30 min to
CH3CN/H2O, 0:100; tR = 8.9 min). Appropriate fractions were col-
lected and the solvent evaporated. The remaining white solid was
dissolved in water (15 mL) and stirred with Amberlite IR-120 ion-
exchange resin (Na+ form, 15 mL). The resin was filtered off and
washed three times with water. The aqueous solution was lyophi-
lized to yield the product as a pale-yellow powder; yield 125.6 mg
stereomeric mixture all signals in the 1H and 13C{1H} NMR occur
twice. H NMR (CDCl3): δ = 5.53 (m, 2 H, 1-H), 4.61 (m, 2 H, 3-
1
H), 4.32 (m, 2 H, 2-H), 4.22 (m, 2 H, 4-H), 4.13 (m, 2 H, 5-H), 4.0
3
(m, 4 H, CH2O), 3.70 (d, JHP = 14.2 Hz, 6 H, POCH3), 3.4–1.9
(m, 20 H, 2 C2B10H10), 1.49 (br. s, 2 H, CH3), 1.47 (br. s, 3 H,
CH3), 1.38 (br. s, 4 H, CH3), 1.36 (br. s, 6 H, CH3), 1.26 (br. s, 9
H, CH3) ppm. 13C{1H} NMR (CDCl3): δ = 109.6–108.8 (Cquat of
isopropylidene), 96.2 (C-1), 75.2 (s, CB10H10C-CB10H10C), 70.7–
1
(49%). H NMR (D2O): δ = 5.20 (m, 2ϫ0.33 H, 1α-H), 4.55 (m,
3JHH = 7.5 Hz, 2ϫ0.67 H, 1β-H), 4.14 (s, 2ϫ0.33 H, 5α-H), 3.97
70.4 (m, C-2, C-3, and C-4), 67.5 (d, JCP = 6.5 Hz, C-5), 67.0 (d,
3
(m, 4 H, CH2O, α + β form), 3.90 (s, 2 H, 2α-H + 4β-H), 3.82 (m, 2JCP = 8.2 Hz, C-6), 66.7 (d, JCP = 132.3 Hz, PCB10H10C-
4ϫ0.33 H, 3α-H and 4α-H), 3.74 (m, 2ϫ0.67 H, 5β-H), 3.60 (d, CB10H10CP), 54.7 (d, 2JCP = 6.5 Hz, OCH3), 26.1–24.4 (CH3) ppm.
1
3JHH = 8.5 Hz, 2ϫ0.67 H, 3β-H), 3.42 (m, 2ϫ0.67 H, 2β-H), 3.4–
1.6 (br. m, 20 H, 2 C2B10H10) ppm. 13C{1H} NMR (D2O): δ = 96.5
31P{1H} NMR (CDCl3): δ = 79.2 (s), 79.0 (s) (diastereomers) ppm.
1
11B NMR (CDCl3): δ = –10.6 (br. s, JBH n.d., 20 B) ppm. IR
(C-1β), 92.4 (C-1α), 76.5 (s, CB10H10C-CB10H10C), 73.6 (3JCP
=
(KBr): ν = 2989 (m), 2937 (m, C–H), 2621 (s, B–H), 1860 (w), 1456
˜
1
7.6 Hz, C-5β), 72.6 (C-3β), 71.8 (C-2β), 70.9 (d, JCP = 153.3 Hz,
(w), 1382 (m), 1306 (w), 1256 (m), 1213 (w), 1171 (m), 1146 (w),
1072 (w), 1029 (w), 1006 (w), 905 (w), 888 (w), 838 (m), 768 (w),
PCB10H10C-CB10H10CP), 69.2 (3JCP = 7.2 Hz, C-5α), 69.0 and 68.9
(C-3α and C-4α), 68.3 (C-4β), 68.2 (C-2α), 65.5 (2JCP = 6.1 Hz, C- 730 (w), 691 (w), 665 (w), 608 (w), 570 (w), 512 (w), 492 (w) cm–1.
6α), 64.8 (2JCP = 5.7 Hz, C-6β) ppm. 31P{1H} NMR (D2O): δ =
MS (ESI positive in CH3 CN): m/z = 1014.6 [M + Na]+.
C30H64B20O14P2S2·3H2O (1045.17): calcd. C 34.48, H 6.75; found
1
4.3 (s), 4.2 (s) ppm. 11B NMR (D2O): δ = –11.2 (br. s, JBH n.d.,
20 B) ppm. IR (KBr): ν = 3424 (s, OH), 2924 (w), 2857 (w, CH), C 33.64, H 7.00.
˜
2620 (BH), 1686 (m), 1636 (w), 1444 (w), 1384 (w), 1210 (s), 1145
Diastereomeric Mixture of Disodium O,OЈЈ-Bis(6-deoxy-D-galacto-
(m), 1088 (m), 1042 (w), 880 (w), 840 (w), 804 (w), 726 (w), 636
(w), 607 (w), 547 (m) cm–1. MS (ESI positive in H2O/CH3OH): m/z
= 837.37 [M + Na]+, 854.34 [M + K]+, 869.32 [M + CH3OH +
Na]+. C16H42B20Na2O16P2 (814.64): calcd. C 23.59, H 5.20; found
C 22.98, H 4.99.
pyranos-6-yl)-{1,1Ј-bi[1,7-dicarba-closo-dodecaborane(12)]-7,7Ј-
diyl}bis(phosphonothioate) (10): Triethylamine (0.5 mL, 3.6 mmol)
and thiophenol (0.25 mL, 2.4 mmol) were added to a stirred solu-
tion of 6 (312 mg, 0.31 mmol) in 1,4-dioxane (1 mL). The reaction
mixture was stirred for 1 h at room temperature. Then all volatiles
were evaporated and ethyl acetate was added several times (5 mL
each time) to the resulting residue to remove thiophenol (evapo-
rates azeotropically with ethyl acetate). The oily residue was dis-
solved in dichloromethane (50 mL) and stirred with Amberlite IR-
120 ion-exchange resin (H+ form, 50 mL) for 50 min. The resin was
filtered off and washed three times with dichloromethane (50 mL).
The combined extracts were evaporated to dryness, trifluoroacetic
acid (4 mL, 90% in water) was added, and stirring was continued
for 40 min at room temperature. The solvent was evaporated and
the residue extracted several times with ethyl acetate (5 mL each
time). Purification was performed by preparative HPLC on a Pron-
toSIL® column (gradient CH3CN/H2O, 80:20 over 30 min to
CH3CN/H2O, 0:100; tR = 15.0 min). Appropriate fractions were
collected and concentrated in vacuo. The residue was lyophilized
several times. The resulting white powder was dissolved in water
(15 mL) and stirred with Amberlite IR-120 ion-exchange resin
(Na+ form, 10 mL) for 48 h. The resin was filtered off and washed
three times with water (10 mL). The aqueous solution was lyophi-
lized to yield the product as a pale-yellow powder (162.2 mg, 61%).
Due to the formation of diastereomers all NMR signals occur
Deprotection with
Thiophenol/Triethylamine: Triethylamine
(0.5 mL, 3.6 mmol) and thiophenol (0.25 mL, 2.4 mmol) were
added to a stirred solution of 5 (327 mg, 0.34 mmol) in 1,4-dioxane
(1 mL). The reaction mixture was stirred for 1 h at room tempera-
ture. Then all the volatile materials were evaporated and ethyl acet-
ate was added to the resulting residue to remove thiophenol (can
be distilled azeotropically with ethyl acetate). The residue was dis-
solved in trifluoroacetic acid (4 mL, 90% in water) and stirred for
40 min at room temperature. The reaction mixture was evaporated
to dryness and the residue purified by preparative HPLC on a
ProntoSIL® column (gradient CH3CN/H2O, 80:20 over 30 min to
CH3CN/H2O, 0:100; tR = 11.0 min). Appropriate fractions were
collected and concentrated in vacuo. The residue was lyophilized
several times. The resulting white powder was dissolved in water
(15 mL) and stirred with Amberlite IR-120 ion-exchange resin
(Na+ form, 10 mL) for 48 h. The resin was filtered off and washed
three times with water (10 mL). The aqueous solution was lyophi-
lized to yield the product as a pale-yellow powder (55.2 mg, 20%).
The analytical data are identical to the data mentioned above.
(RP1,SP1:RP2,SP2)-O,OЈЈ-Bis(1,2:3,4-di-O-isopropylidene-6-deoxy-α-
D
-galactopyranos-6-yl)-OЈ,OЈЈЈ-dimethyl-{1,1Ј-bi[1,7-dicarba-closo- manifold. The signals of the protons and carbon atoms of the gal-
dodecaborane(12)]-7,7Ј-diyl}bis(phosphonothioate) (6): Compound 2
(0.27 g, 0.54 mmol) was suspended in acetonitrile (7 mL). Then
1,2:3,4-di-O-isopropylidene-α--galactopyranose (2) in acetonitrile
(2.0 mL, 1.60 mmol, 0.8 ) and benzimidazolium triflate (0.36 g,
1.35 mmol) were added. The reaction mixture was heated at reflux
until the solid had dissolved and then stirred for 3 h at room tem-
perature. Conversion was monitored by 31P{1H} NMR spec-
troscopy. Then powdered Beaucage reagent (0.22 g, 1.10 mmol) was
added and stirring was continued for 2 h at room temperature. The
reaction mixture was diluted with ethyl acetate (20 mL) and ex-
tracted with brine (3ϫ20 mL). The organic layer was dried with
anhydrous MgSO4 and the solvent removed under reduced pres-
sure. The honey-like residue was purified by chromatography on
silica gel with ethyl acetate/cyclohexane (1:2). The product was ob-
tained as a white foam (0.22 g, 41%) after treatment with diethyl
ether. Rf (ethyl acetate/cyclohexane, 1:2) = 0.49. Due to the dia-
actopyranosyl moieties could not be assigned with certainty. 1H
3
NMR (D2O): δ = 5.24 (m, 2ϫ0.33 H, 1α-H), 4.63 (m, JHH n.d.,
2ϫ0.67 H, 1β-H), 4.22 (s, 2ϫ0.33 H, 5α-H), 4.10 (m, 4 H, CH2O,
α + β form), 4.00 (s, 2 H, 2α-H + 4β-H), 3.88–3.77 (m, 2.66 H, 4α-
H, 3α-H, 5β-H), 3.71 (d, 3JHH = 8.5 Hz, 2ϫ0.67 H, 3β-H), 3.46 (m,
2ϫ0.67 H, 2β-H), 3.4–1.6 (br. m, 20 H, 2 C2B10H10) ppm. 13C{1H}
1
NMR (D2O): δ = 96.5 (C-1β), 92.4 (C-1α), 77.5 (d, JCP
=
106.7 Hz, PCB10H10C-CB10H10CP), 75.0 (s, CB10H10C-CB10H10C),
3
73.6 (3JCP = 8.9 Hz, C-5β), 72.6 (C-3β), 71.9 (C-2β), 69.1 (m, JCP
n.d., C-5α), 68.5 and 68.4 (C-3α + C-4α), 68.2 (C-2α + C-4β), 65.1
2
(2JCP n.d., C-6α), 64.0 (m, JCP n.d., C-6β) ppm. 31P{1H} NMR
(D2O): δ = 60.5 (s), 60.6 (s) (diastereomers) ppm. 11B NMR (D2O):
1
δ = –10.9 (br. s, JBH n.d., 20 B) ppm. IR (KBr): ν = 3416 (s, O–
˜
H), 2928 (w, C–H), 2617 (B–H), 1637 (m), 1407 (m), 1368 (w), 1206
(w), 1138 (m), 1091 (w), 1040 (w), 870 (w), 813 (w), 771 (w), 729
(w), 650 (w), 617 (w), 462 (w), 419 (w) cm–1. MS (ESI positive in
3136
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Eur. J. Org. Chem. 2010, 3129–3139