P. Rajasekaran et al.
Carbohydrate Research 500 (2021) 108254
chromatography (hexane:ethyl acetate, 10:1) afforded the enol ester as
an E/Z mixture (1:22) (780 mg, 62% yield) as a yellow oil. 1H NMR (600
MHz, CDCl3) δ 7.38–7.27 (m, 15H), 7.19 (d, J = 1.8 Hz, 1H, H-6),
4.91–4.82 (m, 3H, PhCH2), 4.80–4.73 (m, 2H, PhCH2), 4.70 (d, J = 3.4
Hz, 1H, H-1), 4.66 (d, J = 12.2 Hz, 1H, PhCH2), 4.03–3.93 (m, 2H, H-4,
H-3), 3.59 (dd, J = 8.5, 3.4 Hz, 1H, H-2), 3.48 (s, 3H, OCH3), 2.66 (sept,
J = 7.0 Hz, 1H, H-7), 1.21 (dd, J = 7.0, 1.8 Hz, 6H, CH(CH3)2)⋅13C NMR
(151 MHz, CDCl3) δ 173.5 (CO), 138.5 (ArC), 138.0 (ArC), 137.6 (ArC),
134.8 (ArC), 128.50 (ArC), 128.48 (ArC), 128.4 (ArC), 128.01 (ArC),
128.0 (ArC), 127.97 (ArC), 127.9 (ArC), 127.7 (ArC), 123.1 (C-6), 99.7
(C-1), 81.3 (C-3), 79.0 (C-2), 77.9 (C-4), 75.7 (PhCH2), 74.6 (PhCH2),
73.7 (PhCH2), 56.1 (OCH3), 33.8 (C-7), 18.9 (CH(CH3)2), 18.7 (CH
(CH3)2). HRMS (ESI): m/z calcd for C32H36O7Na [M + Na] 555.2353,
found 555.2339.
Hz, 1H, H-3), 3.62 (d, J = 9.1 Hz, 1H, H-4), 3.58 (dd, J = 9.6, 3.9 Hz, 1H,
H-2), 3.48 (s, 3H, OMe), 1.58 (s, 3H, CH3)⋅13C NMR (150 MHz, CDCl3) δ
198.9 (CHO), 138.5 (ArC), 138.0 (ArC), 137.9 (ArC), 128.55 (ArC),
128.46 (ArC), 128.44 (ArC), 128.43 (ArC), 128.41 (ArC), 128.39 (ArC),
128.38, 128.15 (ArC), 128.13 (ArC), 128.09 (ArC), 128.05 (ArC),
128.04 (ArC), 128.95 (ArC), 127.85 (ArC), 127.77 (ArC), 99.9 (C-1),
81.3 (C-5), 79.6 (C-4), 78.4 (C-2), 78.3 (C-3), 75.9 (PhCH2), 75.3
(PhCH2), 73.6 (PhCH2), 56.4 (OCH3), 16.4 (CH3). HRMS (ESI): m/z
calcd for C29H32O6Na [M + Na] 499.2091, found 499.2077.
Methyl 2,3,4-Tri-O-benzyl-5-C-methyl-β-L-idopyranoside 6. A
solution of aldehyde 4 (20 mg, 0.1 mmol) in methanol (1 mL) was
treated with sodium borohydride (5 mg, 0.34 mmol) at 0 ◦C and stirred
for 1 h before the solvent was removed under vacuum and the residue
purified by column chromatography (hexane:ethyl acetate, 3:1) to
Methyl
2,3,4-Tri-O-benzyl-6-O-isobutyroyl-5,6-methanediyl-
afford the alcohol 6 (16 mg, 80%) as colorless oil. [
α]
D
22 = ꢀ 12.9 (c 0.35,
1
α
-D-glucopyranoside (3). A solution of compound 2 (750 mg, 1.41
CH2Cl2); H NMR (600 MHz, CDCl3) δ 7.40–7.29 (m, 15H, ArH), 5.00
(dd, J = 13.3, 10.9 Hz, 2H, PhCH2), 4.85 (dd, J = 12.5, 11.2 Hz, 2H,
PhCH2), 4.67 (dd, J = 11.6, 7.1 Hz, 2H, PhCH2), 4.58 (d, J = 4.2 Hz, 1H,
H-1), 4.27 (t, J = 9.7 Hz, 1H, H-3), 3.92 (dd, J = 12.0, 3.1 Hz, 1H, H-6a),
3.65 (dd, J = 12.0, 10.4 Hz, 1H, H-6b), 3.55 (dd, J = 9.9, 4.2 Hz, 1H, H-
2), 3.50 (s, 3H, OCH3), 3.45 (d, J = 9.5 Hz, 1H, H-4), 3.18 (dd, J = 10.4,
3.2 Hz, 1H, OH), 1.25 (s, 3H, CH3). 13C NMR (151 MHz, CDCl3) δ 138.7
(ArC), 138.07 (ArC), 138.04 (ArC), 128.55 (ArC), 128.48 (ArC), 128.44
(ArC), 128.1 (ArC), 128.04 (ArC), 128.02 (ArC), 127.91 (ArC), 127.88
(ArC), 127.7 (ArC), 99.4 (C-1), 86.0 (C-4), 80.2 (C-5), 79.2 (C-2), 78.9
(C-3), 76.4 (PhCH2), 75.8 (PhCH2), 73.6 (PhCH2), 66.9 (C-6), 57.1
(OCH3), 24.3 (CH3). HRMS (ESI): m/z calcd for C29H34O6Na [M + Na]
501.2248, found 501.2232.
mmol) in 1,2-dichloroethane (12 mL) was treated with 4 Å molecular
sieves and diiodomethane (1.14 mL, 14.1 mmol), followed by stirring at
room temperature for 0.5 h, before dropwise addition of a solution of
diethylzinc (1 M in hexane, 7.05 mL, 7.05 mmol). The reaction mixture
was heated to 50 ◦C for 24 h then was diluted with dichloromethane (30
mL), filtered and quenched with saturated Na2CO3 solution. The
aqueous layer was extracted with dichloromethane (3 x 15 mL), and the
combined organic phases dried over Na2SO4 and evaporated to dryness.
Purification by column chromatography (hexane:ethyl acetate, 10:1)
afforded the target compound as an inseparable mixture of di-
astereomers (550 mg, 71% yield) as a yellow oil. Major isomer: 1H NMR
(600 MHz, CDCl3) δ 7.48–7.13 (m, 15H), 4.97 (d, J = 11.0 Hz, 1H,
PhCH2), 4.90 (d, J = 11.0 Hz, 1H, PhCH2), 4.85–4.80 (m, 2H, PhCH2),
4.70–4.64 (m, 2H, PhCH2), 4.63 (d, J = 3.9 Hz, 1H, H-1), 3.97 (t, J = 9.3
Hz, 1H, H-3), 3.90 (dd, J = 7.9, 4.4 Hz, 1H, H-6), 3.86 (d, J = 9.1 Hz, 1H,
H-4), 3.66 (dd, J = 9.5, 3.9 Hz, 1H, H-2), 3.41 (s, 3H, OCH3), 2.60 (sept,
J = 7.0 Hz, 1H, H-8), 1.52–1.45 (m, 1H, H-7a), 1.19 (dd, J = 7.0, 0.8 Hz,
6H,-CH(CH3)2, 0.97 (dd, J = 7.7, 4.5 Hz, 1H, H-7b).13C NMR (151 MHz,
CDCl3) δ 177.9 (CO), 138.8 (ArC), 138.2 (ArC), 138.1 (ArC), 128.5
(ArC), 128.47 (ArC), 128.41 (ArC), 128.38 (ArC), 128.36 (ArC), 128.35
(ArC), 128.1 (ArC), 128.09 (ArC), 127.97 (ArC), 127.95 (ArC), 127.9
(ArC), 127.7 (ArC), 127.64 (ArC), 127.60 (ArC), 127.57 (ArC), 127.5
(ArC), 100.3 (C-1), 81.1 (C-3), 80.0 (C-2), 77.6 (C-4), 75.7 (PhCH2), 75.3
(PhCH2), 73.6 (PhCH2), 56.5 (C-5), 55.5 (OCH3), 49.7 (C-6), 33.7 (C-8),
19.0 (CH(CH3)2), 18.8 (CH(CH3)2), 13.7 (CH2-7). HRMS (ESI): m/z calcd
for C33H38O7Na [M + Na] 569.2510, found 569.2499.
Methyl 2,3,4-Tri-O-benzyl-5-C-methyl-α-D-glucopyranoside 7. A
solution of aldehyde 5 (46 mg, 0.1 mmol) in methanol (2 mL) was
treated with sodium borohydride (11 mg, 0.29 mmol) at 0 ◦C and stirred
for 1 h before the solvent was removed under vacuum and the residue
purified by column chromatography (hexane:ethyl acetate, 3:1) to
afford the alcohol 7 (42 mg, 91%) as colorless oil. [
α
]
22 = +8.4 (c 0.25,
CH2Cl2); 1H NMR (600 MHz, C6D6) δ 7.33–7.01D(m, 15H, ArH),
5.01–4.96 (m, 2H, PhCH2), 4.78 (d, J = 11.3 Hz, 1H, PhCH2), 4.64 (d, J
= 11.3 Hz, 1H, PhCH2), 4.57 (d, J = 12.0 Hz, 1H, PhCH2), 4.54 (d, J =
4.0 Hz, 1H, H-1), 4.45 (d, J = 12.0 Hz, 1H, PhCH2), 4.26 (t, J = 9.8 Hz,
1H, H-3), 3.89 (d, J = 9.7 Hz, 1H, H-4), 3.44–3.40 (m, 2H, H-2, H-6a),
3.35–3.26 (m, 1H, H-6a), 3.11 (s, 3H, OCH3), 1.82–1.49 (m, 1H, OH),
1.32 (s, 3H, CH3); 13C NMR (151 MHz, C6D6) δ 139.4 (ArC), 139.1 (ArC),
139.0 (ArC), 128.2 (ArC), 128.13 (ArC), 128.09 (ArC), 127.9 (ArC),
127.8 (ArC), 127.7 (ArC), 127.6 (ArC), 127.2 (ArC), 100.0 (C-1), 81.0
(C-2), 79.0 (C-5), 78.8 (C-3), 78.7 (C-4), 75.5 (PhCH2), 75.2 (PhCH2),
72.6 (PhCH2), 67.4 (C-6), 55.4 (OCH3), 18.4 (CH3). HRMS (ESI): m/z
calcd for C29H34O6Na [M + Na] 501.2248, found 501.2237.
Methyl 2,3,4-Tri-O-benzyl-5-C-methyl-β-L-ido-hexodialdo-1,5-
pyranoside 4 and Methyl 2,3,4-Tri-O-benzyl-5-C-methyl-α-D-gluco-
hexodialdo-1,5-pyranoside 5. Potassium carbonate (556 mg, 4.03
mmol) was added to a solution of 3 (220 mg, 0.40 mmol) in a 15:1
mixture of methanol/water (5 mL). The reaction mixture was stirred for
12 h at room temperature, then was diluted with ethyl acetate (20 mL)
and water (20 mL). The aqueous layer was extracted with ethyl acetate
(3x 10 mL). The combined organic layers were washed with brine, dried
over Na2SO4, filtered and concentrated to dryness. Purification by col-
umn chromatography (hexane:ethyl acetate, 10:2) afforded both alde-
hydes 4 (30 mg, 15% yield) and 5 (148 mg, 77% yield) as colorless oils.
Methyl 5-C-methyl-α-D-glucopyranoside 8. Pd(OH)2/C (30% w/
w, 5 mg) was added to a solution of 7 (15 mg, 0.03 mmol) in methanol
(1 mL), and the suspension degassed and stirred vigorously under 1 atm
of H2 (balloon) for 24 h, after which it was filtered through a Celite pad,
which was washed with MeOH. Evaporation of the solvent which on
repeated washing with hexane:ethyl acetate (3:1) gave the title com-
pound (8 mg, 92%). [
α]
22 = +60.0 (c 0.1, CH2Cl2); 1H NMR (900 MHz,
D
4: [
α
]
22 = +20.0 (c 0.10, CH2Cl2); 1H NMR (600 MHz, CDCl3) δ 9.90
D2O) δ 4.75 (d, J = 4.2 Hz, 1H, H-1), 3.78 (t, J = 9.9 Hz, 1H, H-3), 3.52
(d, J = 9.8 Hz, 1H, H-4), 3.47 (dd, J = 10.0, 4.2 Hz, 1H, H-2), 3.46–3.38
(m, 2H, H-6a, H-6b), 3.36 (s, 3H, OCH3), 1.17 (s, 3H, CH3). 13C NMR
(225 MHz, D2O) δ 100.7 (C-1), 79.3 (C-5), 71.5 (C-2), 70.7 (C-4), 69.3
(C-3), 66.2 (C-6), 55.7 (OCH3), 16.9 (CH3)). HRMS (ESI): m/z calcd for
C8H16O6Na [M + Na] 231.0839, found 231.0833.
(s, 1H), 7D.39–7.26 (m, 15H), 5.04 (d, J = 10.7 Hz, 1H, PhCH2), 4.98 (d, J
= 11.3 Hz, 1H, PhCH2), 4.89–4.80 (m, 2H, PhCH2), 4.68 (dd, J = 13.2,
11.6 Hz, 2H, PhCH2), 4.48 (d, J = 3.6 Hz, 1H, H-1), 4.31 (t, J = 9.6 Hz,
1H, H-3), 3.53 (dd, J = 9.7, 3.6 Hz, 1H, H-2), 3.51 (d, J = 9.5 Hz, 1H, H-
4), 3.24 (s, 3H, OCH3), 1.28 (s, 3H, CH3)⋅13C NMR (150 MHz, CDCl3) δ
199.5 (CHO), 151.1, 138.5, 137.9, 137.8, 128.6, 128.5, 128.4, 128.1,
128.0, 127.8, 127.8, 127.7, 99.3, 83.4, 80.1, 79.1, 77.3, 76.2, 75.9, 73.6,
56.3, 21.4. HRMS (ESI): m/z calcd for C29H32O6Na [M + Na] 499.2097,
found 499.2083.
Penta-O-acetyl-5-bromo-β-D-glucopyanose (10). This compound
was prepared according to the literature method [23] from glucose
22
pentaacetate in 89% yield as colorless syrup. [
α]
= ꢀ 28.8 (c 0.25,
D
CH2Cl2); 1H NMR (600 MHz, CDCl3) δ 6.25 (d, J = 8.6 Hz, 1H), 5.59 (t, J
= 9.7 Hz, 1H), 5.28 (dd, J = 9.7, 8.6 Hz, 1H), 5.26 (d, J = 9.7 Hz, 1H),
4.59 (d, J = 12.3 Hz, 1H), 4.33 (d, J = 12.3 Hz, 1H), 2.14 (s, 3H), 2.13 (s,
3H), 2.09 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H); 13C NMR (151 MHz, CDCl3)
5: [α
]
22 = +104.0 (c 0.75, CH2Cl2); 1H NMR (600 MHz, CDCl3) δ 9.35
(s, 1H), 7D.42–7.26 (m, 15H), 5.01–4.80 (m, 4H, PhCH2), 4.75 (d, J = 3.9
Hz, 1H, H-1), 4.65 (dd, J = 67.3, 11.5 Hz, 2H, PhCH2), 4.14 (t, J = 9.4
4