Synthesis and Conformation of the Disaccharide ManaACHTUNTRGNEU(GN 1,6)-C-ManaOPh
FULL PAPER
698, 753 cmꢀ1 (m, d(CH)); ESI+-HRMS: m/z: calcd for C51H51N2O9S:
867.3310 [M+H]+, found: 867.3315. Diastereomer 1; 42%, yellowish oil;
Rf =0.4 (petroleum ether/ethyl acetate 3:2); [a]D20 =+48 (c=0.9 in
(3ꢅ90 mL). After concentration to dryness, purification by flash column
chromatography (petroleum ether/ethyl acetate, gradient elution) gave
alkene 10 (1.83 g, 65%) as a colourless oil. Rf =0.9 (petroleum ether/
ethyl acetate 1:1); [a]D20 =+30 (c=0.4 in CHCl3); 1H NMR (500 MHz,
C6D6): d=1.30–1.37 (m, 1H; 7a-H), 1.75–1.84 (m, 2H; 6a-H, 7’a-H),
CHCl3); 1H NMR (500 MHz, C6D6): d=2.06 (ddd, 2J
(H,H)=9.5, 2.0 Hz, 1H; 7a-H), 2.25 (ddd, 2J
11.0, 2.0 Hz, 1H; 7’a-H), 3.37 (at, 2J(H,H)=10.0 Hz, 3J
1H; 6b-H), 3.48 (ddd, 3J
(H,H)=10.0, 8.0, 4.5 Hz, 1H; 5b-H), 3.84 (brdd,
3J
(H,H)=8.0, 2.5 Hz, 1H; 4b-H), 3.88 (dd, J
H), 3.96 (dd, 2J(H,H)=10.0 Hz, 3J
(H,H)=4.5 Hz, 1H; 6’b-H), 4.10 (at,
3J
(H,H)=9.5, 9.5 Hz, 1H; 4a-H), 4.16 (dd, J
H), 4.29 (brdat, 3J(H,H)=11.0, 11.0, 2.0 Hz, 1H; 1b-H), 4.39 (d, 2J-
(H,H)=11.5 Hz, 1H; CH2Bn), 4.43 (d, 2J
(H,H)=11.5 Hz, 1H; CH2Bn),
4.50 (d, 2J(H,H)=12.0 Hz, 1H; CH2Bn), 4.51 (dd, 3J
(H,H)=9.5, 2.0 Hz,
1H; 5a-H), 4.56 (d, 2J(H,H)=11.0 Hz, 1H; CH2Bn), 4.62 (d, 2J
(H,H)=
12.0 Hz, 1H; CH2Bn), 4.90 (d, J(H,H)=11.0 Hz, 1H; CH2Bn), 5.22 (dat,
3J(H,H)=11.0, 2.5, 2.5 Hz, 1H; 2b-H), 5.25 (s, 1H; 7b-H), 5.56 (d, 3J-
(H,H)=2.0 Hz, 1H; 1a-H), 5.89 (brd, J
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
1.93–1.99 (m, 1H; 6’a-H), 3.52 (at, 2J
1H; 6b-H), 3.58 (ddd, 3J
(H,H)=14.5, 10.0, 4.0 Hz, 1H; 5b-H), 3.86–3.94
(m, 4H; 2a-H, 5a-H, 1b-H, 4b-H), 3.96 (at, J
H), 4.11 (dd, 2J(H,H)=10.0 Hz, 3J
(H,H)=4.0 Hz, 1H; 6’b-H), 4.20 (dd,
3J(H,H)=9.0, 3.0 Hz, 1H; 3a-H), 4.47 (d, 2J
(H,H)=11.5 Hz, 1H;
CH2Bn), 4.50 (d, 2J(H,H)=13.5 Hz, 1H; CH2Bn), 4.50 (d, 2J
(H,H)=
13.5 Hz, 1H; CH2Bn), 4.53 (d, 2J
(H,H)=12.0 Hz, 1H; CH2Bn), 4.62 (d,
2J
(H,H)=12.0 Hz, 1H; CH2Bn), 4.96 (d, J
5.21 (dat, 3J
(H,H)=10.5, 2.5, 2.5 Hz, 1H; 2b-H), 5.31 (s, 1H; 7b-H), 5.64
(d, 3J(H,H)=1.5 Hz, 1H; 1a-H), 5.87 (d, 3J
(H,H)=10.5 Hz, 1H; 3b-H),
6.83 (atat, 3J
(H,H)=7.0, 7.0 Hz, 1.0 Hz, 1.0 Hz, 1H; ArH), 7.04–7.19 (m,
(H,H)=10.0 Hz, 3J
ACHUTGTNRENNUG ACHUTTGNREN(NUGN H,H)=10.0 Hz,
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
3
3
AHCTUNGERTG(NNUN H,H)=9.0, 9.0 Hz, 1H; 4a-
A
ACHTUNGERTN(NUNG H,H)=3.0, 2.0 Hz, 1H; 2a-
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
A
ACHTUNGTRENNUNG
A
ACHTUNGERTN(NUNG H,H)=9.5, 3.0 Hz, 1H; 3a-
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
2
A
ACHTUNGTREN(UNGN H,H)=11.5 Hz, 1H; CH2Bn),
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
2
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
3
16H; 16ArH), 7.30–7.36 (m, 6H; 6ArH), 7.60–7.62 ppm (m, 2H; 2ArH);
13C NMR (125.8 MHz, C6D6): d=28.2 (C-6a), 28.9 (C-7a), 65.5 (C-5b),
69.9 (C-6b), 71.9 (C-2a), 72.4 (CH2Bn), 73.4 (CH2Bn, C-1b), 75.3
(CH2Bn), 75.8 (C-5a), 75.9 (C-4b), 79.0 (C-4a), 80.7 (C-3a), 96.4 (C-1a),
102.0 (C-7b), 116.7 (2ArCH), 122.5 (ArCH), 126.6 (C-3b), 126.9
(2ArCH), 127.7 (ArCH), 127.8 (ArCH), 127.9 (2ArCH), 127.9 (2ArCH),
128.0 (2ArCH), 128.2 (2ArCH), 128.3 (2ArCH), 128.5 (2ArCH), 128.6
(2ArCH, ArCH), 128.9 (ArCH), 129.8 (2ArCH), 131.2 (C-2b), 138.7
(ArC), 138.8 (ArC), 139.1 (ArC), 139.3 (ArC), 156.5 ppm (ArC phenyl);
A
ACHTUNGTNER(NUNG H,H)=11.0 Hz, 1H; 3b-H), 6.38
3
3
(dat, JACHTUNGTRENNUNG(H,H)=9.5, 2.0, 2.0 Hz, 1H; 6a-H), 6.80 (at, JACHTUNGTERN(NUGN H,H)=7.0, 7.0 Hz,
1H; ArH), 6.86 (brs, 1H; ArH), 6.92–6,94 (m, 2H; 2ArH), 6.98–7.02 (m,
2H; 2ArH), 7.05–7.24 (m, 13H; 13ArH), 7.30–7.35 (m, 4H; 4ArH), 7.46–
7.48 (m, 2H; 2ArH), 7.59–7.61 (m, 2H; 2ArH), 8.14 ppm (s, 1H; ArH);
13C NMR (125.8 MHz, C6D6): d=31.3 (C-7a), 65.5 (C-5b), 69.5 (C-6b),
70.5 (C-1b), 72.5 (C-5a), 72.5 (CH2Bn), 73.5 (CH2Bn), 75.0 (CH2Bn), 75.3
(C-4a), 74.3 (C-4b), 75.5 (C-2a), 79.7 (C-6a), 80.5 (C-3a), 96.7 (C-1a),
101.9 (C-7b), 116.8 (2ArCH), 118.4 (ArCH), 123.2 (ArCH), 126.8
(2ArCH), 127.9 (C-3b), 127.9 (ArCH), 128.0 (2ArCH), 128.0 (ArCH),
128.1 (2ArCH), 128.2 (ArCH), 128.3 (2ArCH), 128.4 (2ArCH), 128.7
(2ArCH), 128.7 (2ArCH), 128.7 (2ArCH), 128.9 (ArCH), 129.7
(2ArCH), 130.0 (C-2b), 131.1 (ArCH), 136.4 (ArCH), 138.5 (ArC), 138.6
(ArC), 138.6 (ArC), 138.8 (ArC), 155.8 (ArC phenyl), 183.4 ppm (C=S).
Diastereomer 2; 58% yield, colourless oil; Rf =0.6 (petroleum ether/
ethyl acetate 3:2); [a]D20 =+2 (c=0.7 in CHCl3); 1H NMR (500 MHz,
IR (film): n˜ =3064 (m, n
ACHTUNGTRENNUNG
d(CHAr harmonic)), 1598, 1496 (s, nAHCUTNGTRENNUNG
1096 (s, n(CO)), 753, 697 cmꢀ1 (m, d(CH)); ESI+-HRMS: m/z: calcd for
C47H48O8Na: 763.3241 [M+Na]+, found 763.3244; elemental analysis
calcd (%) for C47H48O8: C 76.19, H 6.53; found: C 76.32, H 6.52.
Phenyl 6a-C-(2b,6b-Anhydro-5b,7b-O-benzylidene-1-deoxy-a-d-glycero-
d-talo-heptit-1-yl)-2,3,4-tri-O-benzyl-6-deoxy-a-d-mannopyranoside
(11a): Alkene 10 (563.9 mg, 761.6 mmol) was dissolved in THF (3 mL)
and water (3.6 mL), and potassium carbonate (319.4 mg, 2.31 mmol) was
then added followed by methanesulfonamide (83.0 mg, 0.87 mmol),
K3Fe(CN)6 (753.3 mg, 2.29 mmol), and tBuOH (3.6 mL). An aqueous so-
lution of potassium osmate dihydrate (302.9 mg, 0.82 mmol in 2 mL) was
then added drop-wise. After 20 h, t.l.c (petroleum ether/ethyl acetate 1:1)
showed complete consumption of the starting material (Rf =0.9) and the
appearance of a major product (Rf =0.2) and a minor product (Rf =0.3).
The reaction was quenched by the addition of sodium sulfite (2.69 g) and
the mixture was then stirred for a further 30 min. The mixture was then
partitioned between ethyl acetate (200 mL) and water (200 mL), and the
aqueous layer was re-extracted with ethyl acetate (200 mL). The com-
bined organic extracts were dried over MgSO4, filtered, and concentrated
in vacuo. Purification by flash column chromatography (petroleum ether/
ethyl acetate 1:1 to 0:1) gave the manno-C-disaccharide 11a (292.26 mg,
C6D6): d=1.69 (ddd, 2J
H), 2.24 (dat, 2J(H,H)=13.5 Hz, 3J
(at, 2J(H,H)=10.0 Hz, 3J(H,H)=10.0 Hz, 1H; 6b-H), 3.68 (dat, 3J-
A
ACHTUNGERTN(NUNG H,H)=10.0, 2.5 Hz, 1H; 7a-
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG ACHTUNTGREN(NUGN H,H)=10.0, 3.0,
(H,H)=13.5, 2.5, 2.5 Hz, 1H; 1b-H), 3.83 (dat, 3J
3.0 Hz, 1H; 5b-H), 3.80–3.85 (m, 2H; 2a-H, 4b-H), 4.05 (brd, 3J
(H,H)=
3
9.5 Hz, 1H; 5a-H), 4.10 (at, J
G
C
(H,H)=10.0 Hz, 3J
ACHUTGTNRNEUNG AHCUTNGTREN(NUGN H,H)=
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
(H,H)=11.5 Hz, 1H; CH2Bn), 4.78 (d, 2J
5.05 (dat, 3J
N
3
3
(d, J
G
ACHTUNGERTN(NUNG H,H)=10.5 Hz, 1H; 3b-H),
6.27 (brdd, 3J
ACHTUNGTRENNUNG
6.91 (brs, 1H; ArH), 7.04–7.07 (m, 2H; 2ArH), 7.09–7.20 (m, 12H;
12ArH), 7.23–7.26 (m, 2H; 2ArH), 7.30–7.37 (m, 5H; 5ArH), 7.59–7.63
(m, 3H; 3ArH), 8.61 ppm (s, 1H, ArH); 13C NMR (125.8 MHz, C6D6)
d=31.4 (C-7a), 65.6 (C-5b), 69.6 (C-6b), 70.4 (C-1b), 70.6 (C-5a), 72.4
(CH2Bn), 73.8 (CH2Bn), 74.0 (C-4a), 75.2 (C-4b), 75.3 (C-2a), 75.4
(CH2Bn), 78.5 (C-6a), 80.7 (C-3a), 95.6 (C-1a), 102.1 (C-7b), 116.5
(2ArCH), 118.1 (2ArCH), 122.7 (2ArCH), 126.9 (C-3b), 127.4 (ArCH),
127.9 (2ArCH), 127.9 (ArCH), 128.0 (ArCH), 128.2 (ArCH), 128.2
(2ArCH), 128.3 (2ArCH), 128.4 (2ArCH), 128.4 (2ArCH), 128.7
(2ArCH), 128.8 (2ArCH), 128.9 (ArCH), 129.7 (ArCH), 129.8 (C-2b),
131.6 (ArCH), 137.4 (ArCH), 138.5 (ArC), 138.6 (ArC), 138.6 (ArC),
138.8 (ArC), 155.5 (ArC phenyl), 183.6 ppm (C=S).
50%) as
(31.44 mg, 5%) as a yellow oil. IR (film): n˜ =3421 (m, n(OH)), 3032 (m,
(CHAr)), 2964 (m, n(CH)), 1700–2000 (w, d(CHAr harmonic)), 1598,
a white amorphous solid and the allo-C-disaccharide 11b
nACHTUNGTRENNUNG
1495 (s,
nACTHUNGTERNNU(G C=CAr)), 1454 (m, d(CH)), 1262, 1095 (s, n(CO)), 801,
696 cmꢀ1 (m, d(CH)).
11a: Rf =0.2 (petroleum ether/ethyl acetate 1:1); [a]D19 =+41 (c=0.1 in
CHCl3); 1H NMR (500 MHz, C6D6): d=1.03–1.09 (m, 1H; 7a-H), 1.60–
1.74 (m, 2H; 6a-H, 7’a-H), 1.79–1.84 (m, 1H; 6’a-H), 2.05 (s, 1H; 2b-
OH), 2.13 (s, 1H; 3b-OH), 3.40 (d, 3J
3.55 (m, 1H; 5b-H), 3.55 (dd, 2J(H,H)=16.0 Hz, 3J
6b-H), 3.67–3.69 (m, 2H; 1b-H, 3b-H), 3.79 (brat, 3J
1H; 4b-H), 3.83 (dat, 3J(H,H)=9.5, 9.5, 2.0 Hz, 1H; 5a-H), 3.94 (dd, 3J-
(H,H)=3.0, 2.0 Hz, 1H; 2a-H), 3.94 (at, 3J
(H,H)=9.5, 9.5 Hz, 1H; 4a-
H), 4.11 (dd, 2J(H,H)=16.0 Hz, 3J
(H,H)=10.5 Hz, 1H; 6’b-H), 4.18 (dd,
3J(H,H)=9.5, 3.0 Hz, 1H; 3a-H), 4.47 (d, 2J
(H,H)=12.0 Hz, 1H;
CH2Bn), 4.51 (d, 2J(H,H)=11.5 Hz, 1H; CH2Bn), 4.53 (d, 2J
(H,H)=
12.0 Hz, 1H; CH2Bn), 4.55 (d, 2J
(H,H)=12.5 Hz, 1H; CH2Bn), 4.63 (d,
2J
(H,H)=12.5 Hz, 1H; CH2Bn), 4.99 (d, J
5.27 (s, 1H; 7b-H), 5.64 (d, 3J(H,H)=2.0 Hz, 1H; 1a-H), 6.84 (at, 3J-
(H,H)=7.5 Hz, 1H; ArH), 6.99–7.58 ppm (m, 24H; 24ArH); 13C NMR
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Phenyl
6a-C-(2b,6b-Anhydro-5b,7b-O-benzylidene-1,3,4-trideoxy-a-d-
AHCTUNGTRENNUNG
glycero-d-manno-heptit-3-en-1-yl)-2,3,4-tri-O-benzyl-6-deoxy-a-d-manno-
pyranoside (10): Under an atmosphere of argon, thiocarbonates 9b
(3.30 g, 3.80 mmol) were suspended in anhydrous degassed toluene
(180 mL). Pentafluorophenol (1.84 g, 9.98 mmol) and Ph3SnH (4.45 g,
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
12.69 mmol) were added, followed by
a catalytic amount of AIBN
A
ACHTUNGTRENNUNG
(96.4 mg, 587.5 mmol) and the reaction mixture was then refluxed in the
dark room. After 1 h 30 min., t.l.c (petroleum ether/ethyl acetate 1:1) in-
dicated complete consumption of the starting material (Rf =0.6, Rf =0.4)
and the formation of a major product (Rf =0.9). The reaction mixture
was then cooled to room temperature, and concentrated in vacuo. The
residue was dissolved in acetonitrile (180 mL), and washed with pentane
AHCTUNGTRENNUNG
2
A
ACHTUNGTREN(UNGN H,H)=11.5 Hz, 1H; CH2Bn),
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(125.8 MHz, C6D6): d=23.9 (C-7a), 27.4 (C-6a), 64.6 (C-5b), 69.2 (C-1b
or C-3b), 69.4 (C-6b), 71.8 (C-5a), 72.4 (CH2Bn), 72.5 (C-2b), 73.5
Chem. Eur. J. 2009, 15, 4057 – 4069
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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