References and Notes
<A NAME="RU05007ST-1A">1a</A>
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<A NAME="RU05007ST-1B">1b</A>
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<A NAME="RU05007ST-2C">2c</A>
Wang YA.
Li JJ.
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Our previous papers on BGL:
<A NAME="RU05007ST-3A">3a</A>
Nemoto H.
Wilson JG.
Nakamura H.
Yamamoto Y.
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<A NAME="RU05007ST-3B">3b</A>
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<A NAME="RU05007ST-3C">3c</A>
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<A NAME="RU05007ST-3D">3d</A>
Yamamoto Y.
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<A NAME="RU05007ST-3E">3e</A>
Nemoto H.
Cai J.
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<A NAME="RU05007ST-3F">3f</A>
Nemoto H.
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<A NAME="RU05007ST-3G">3g</A>
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Nemoto H.
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<A NAME="RU05007ST-3H">3h</A>
Takagaki M.
Ono K.
Oda Y.
Kikuchi H.
Nemoto H.
Iwamoto S.
Cai J.
Yamamoto Y.
Cancer Res.
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<A NAME="RU05007ST-3I">3i</A>
Nemoto H.
Kikuishi J.
Yanagida S.
Kawano T.
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Harashima H.
Kiwada H.
Shibuya M.
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<A NAME="RU05007ST-3J">3j</A>
Nemoto H.
Araki T.
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<A NAME="RU05007ST-4A">4a</A>
In Scheme 15 of ref. 4b, the reaction of 4 and 3 with ECH to afford a mixture of 5 (4 + 4 + ECH) and asymmetrical pentaglycerol (4 + 3 + ECH), is drawn with a plain arrow but not with a dotted arrow. However, the authors
mention in the main text that ‘One can imagine repeating this step to give higher
degree oligomers (pentamer, heptamer,…) with dendrimer-like structures’ (around Scheme
15, our paper
[3a]
[b]
was the only one referenced). Furthermore, no experimental details are provided for
Scheme 15. It is possible that they misread our paper,
[3a]
[b]
or mistakenly used a plain arrow rather than a dotted one. Accordingly, the preparation
(either isolation or identification) of octabenzyl ether 5 has not been demonstrated.
<A NAME="RU05007ST-4B">4b</A>
Cassel S.
Debaig C.
Benvegnu T.
Chaimbault P.
Lafosse M.
Plusquellec D.
Rollin P.
Eur. J. Org. Chem.
2001,
875
<A NAME="RU05007ST-5">5</A>
BGL07 is a heptamer containing triply repetitive glyceryl units. In contrast, compound
16, recently reported by us,
[3j]
contains a doubly repetitive glyceryl unit attached to a disparate trifunctionalized
molecule (iminodiacetic acid). This octabenzyl ether 16 should be called BGL06 (Figure
[2]
).
<A NAME="RU05007ST-6">6</A> Preparation of 10a. See:
Forbes DC.
Ene DG.
Doyle MP.
Synthesis
1998,
879
Preparation of 10b. See:
<A NAME="RU05007ST-7A">7a</A>
Crich D.
Beckwith ALJ.
Chen C.
Yao Q.
Davison IGE.
Longmore RW.
Anaya dePC.
Quintero-Cortes L.
Sandoval-Ramirez J.
J. Am. Chem. Soc.
1995,
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8757
<A NAME="RU05007ST-7B">7b</A>
Carlsen Per HJ.
Soerbye K.
Ulven T.
Aasboe K.
Acta Chem. Scand.
1996,
50:
185
<A NAME="RU05007ST-7C">7c</A>
Based on 1H NMR analysis, it is considered that 10b has a chair form bearing phenyl group at equatorial position, and hydroxyl group
at axial position. The hydroxyl group may have electronic affinity among oxygen atoms
of the 1,3-dioxirane ring as shown in the following Figure
[3]
.
<A NAME="RU05007ST-8">8</A>
Preparation of 11a
To a vigorously stirred mixture of 10a (500 mg, 3.78 mmol), TBAI (61.0 mg, 0.19 mmol), finely ground KOH in a mortar (187.3
mg, 2.84 mmol), and H2O (0.04 mL) was added ECH (87.5 mg, 0.95 mmol) slowly and dropwise. After stirring
for 40 h at 60 °C, the resulting mixture was diluted with EtOAc, and the resulting
suspension was filtered. The filtrate was dried over anhyd K2CO3, and concentrated in vacuo. The residue was purified by silica gel column chromatography
using hexane-EtOAc (1:3) as an eluent to afford 11a as a colorless oil (169.7 mg, 0.53 mmol, 56% yield) and 10a (250 mg, 1.89 mmol, 50% recovered). FT-IR (KBr): 518, 561, 731, 829, 949, 1016, 1086,
1124, 1120, 1254, 1333, 1377, 1452, 1473, 2879, 2973, 3442 cm-1. 1H NMR (400 MHz, CDCl3): δ = 4.04-3.89 (m, 5 H), 3.83-3.73 (m, 4 H), 3.63-3.51 (m, 4 H), 3.49-3.41 (m, 2
H), 2.81 (br s, 1 H), 1.43 (s, 6 H), 1.41 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 98.0 (2 × C), 70.8 (2 × CH), 69.6 (2 × CH2), 69.5 (CH), 62.3 (4 × CH2), 23.5 (2 × CH3), 23.4 (2 × CH3). Anal. Calcd for C15H28O7: C, 56.23; H, 8.81. Found: C, 55.88; H, 8.73.
<A NAME="RU05007ST-9">9</A>
Preparation of 11b
To a mixture of 10b (5.613 g, 31.2 mmol), TBAB (0.518 g, 1.56 mmol), finely ground KOH in a mortar (1.543
g, 31.2 mmol), and H2O (0.04 mL) was added Et2O (adequate amount for stirring). To the resulting suspension was added ECH (0.61
mL, 7.79 mmol) slowly and dropwise while stirring vigorously at r.t. The mixture was
then stirred for 5 h at 40 °C, for 5 h at 60 °C, and then for 17 h at 80 °C. The mixture
was poured into H2O (50 mL), and extracted with EtOAc (5 × 50 mL). The combined organic layers were
washed with brine, dried over anhyd K2CO3, and concentrated in vacuo. The residue was purified by silica gel column chromatography
using hexane-EtOAc (1:4) as an eluent to afford 11b (2.212 g, 5.32 mmol, 73% yield based on conversion of 10b) and 10b (2.955 g, 16.4 mmol, 53% recovered). FT-IR (neat): 700, 750, 800, 839, 916, 980,
1011, 1092, 1153, 1217, 1238, 1277, 1340, 1392, 1454, 2860, 2974, 3477 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.54-7.43 (m, 4 H), 7.40-7.32 (m, 6 H), 5.54 (s, 2 H), 4.41-4.31 (m, 4 H),
4.10-3.98 (m, 5 H), 3.79-3.65 (m, 4 H), 3.77-3.67 (m, 2 H), 2.85 (d, J = 5.6 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 137.9 (2 × C), 128.6 (2 × CH), 127.9 (4 × CH), 125.8 (4 × CH), 100.9 (2 × CH),
70.9 (2 × CH), 69.5 (CH), 69.1 (2 × CH2), 68.7 (4 × CH2). HRMS (EI): m/z calcd for C23H28O7 [M+]: 416.1809; found: 416.1835.
<A NAME="RU05007ST-10">10</A>
The recovered yield of 11 was calculated using the following equation (Equation
[1]
). Accordingly, 50% is the ideal value for entries 1-6, and 0% is the ideal value
for entries 7-9 (Table
[1]
). Equation
[2]
was also used to calculate the yield of 12 since 12 consists of two moieties of 11 and an excess of 11 was used.
<A NAME="RU05007ST-11">11</A>
Compound 12a: FT-IR (neat): 521, 733, 827, 941, 1084, 1120, 1252, 1286, 1375, 1454, 1651, 1716,
2877, 2991, 3417 cm-1. 1H NMR (400 MHz, CDCl3): δ = 4.00-3.86 (m, 9 H), 3.80-3.50 (m, 22 H), 3.48-3.40 (m, 4 H), 1.43 (s, 12 H),
1.40 (s, 4 H). 13C NMR (100 MHz, CDCl3): δ = 98.1 (4 × C), 78.7 (2 × CH), 71.9 (2 × CH2), 70.9 (4 × CH), 69.6 (CH), 68.7, 68.6 (4 × CH2), 62.4, 62.4, 62.3, 62.3 (8 × CH2), 30.9, 29.6, 24.0, 24.0, 23.1, 23.0 (8 × CH3). ESI-HRMS: m/z calcd for C33H60O15Na [M + Na]+: 719.3830; found: 719.3832.
<A NAME="RU05007ST-12">12</A>
Compound 12b: FT-IR (neat): 699, 749, 799, 841, 916, 982, 1011, 1092, 1216, 1238, 1278, 1278,
1344, 1392, 1454, 1496, 1604, 2864, 3034, 3477 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.60-7.44 (m, 8 H), 7.43-7.29 (m, 12 H), 5.60-5.41 (s, 4 H), 4.43-4.22 (m,
8 H), 4.02-3.87 (m, 9 H), 3.85-3.56 (m, 14 H), 3.40-3.25 (s, 4 H). 13C NMR (100 MHz, CDCl3): δ = 137.7 (4 × C), 128.0 (4 × CH), 127.3 (8 × CH), 125.4 (8 × CH), 100.2 (4 × CH),
78.1 (2 × CH), 71.0 (2 × CH2), 70.4 (4 × CH), 69.1 (CH), 68.2, 67.9 (8 × CH2), 67.7, 67.5 (4 × CH2). HRMS-FAB: m/z calcd for C49H61O15 [M + H]+: 889.4018; found: 889.4010.
<A NAME="RU05007ST-13">13</A>
Structure of the glycidyl ether (Figure
[4]
):
<A NAME="RU05007ST-14">14</A>
A molar ratio 11a/ECH = 4:1 was finally applied, otherwise nucleophilic attack by 11a to the glycidyl ether (11a + ECH) slowed down, affording an unidentified mixture and some identified oligomers
such as an asymmetrical tetramer (11a + ECH + H2O) and an asymmetrical undecamer (12a + ECH + 11a = three of 11a + two of ECH).
<A NAME="RU05007ST-15">15</A>
In contrast to the reaction with 11a,
[14]
compounds with high molecular weight such as undecamers, were not detected when 11b was used. Therefore, a molar ration of 11b/ECH = 2:1 was applied.
<A NAME="RU05007ST-16">16</A>
Compound 14a: pale yellow oil. FT-IR (neat): 520, 665, 754, 827, 941, 995, 1087, 1373, 1454, 1553,
1666, 1739, 1783, 1815, 2875, 2941, 2993, 3334, 3508 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.63 (d, J = 8.8 Hz, 1 H), 4.18-4.08 (m, 1 H), 3.98-3.87 (m, 8 H), 3.77-3.64 (m, 10 H), 3.61-3.44
(m, 12 H), 3.42-3.33 (m, 4 H), 2.80 (s, 4 H), 2.65 (t, J = 7.2 Hz, 2 H), 2.30 (t, J = 7.2 Hz, 2 H), 2.03 (quin, J = 7.2 Hz, 2 H), 1.42-1.34 (m, 24 H). 13C NMR (100 MHz, CDCl3): δ = 171.3 (C), 168.9 (2 × C), 168.1 (C), 98.1 (2 × C), 98.0 (2 × C), 78.7 (2 ×
CH), 71.0 (2 × CH), 70.9 (2 × CH), 68.8 (2 × CH2), 68.7 (2 × CH2), 68.6 (2 × CH2), 62.5 (4 × CH2), 62.3 (2 × CH2), 62.2 (2 × CH2), 49.3 (CH), 34.3 (CH2), 30.0 (CH2), 25.5 (2 × CH2), 23.9 (2 × CH3), 23.6 (2 × CH3), 23.6 (2 × CH3), 23.3 (2 × CH3), 20.5 (CH2). ESI-HRMS: m/z calcd for C42H70N2O19Na [M + Na]+: 929.4470; found: 929.4470.
Compound 14b: pale yellow oil. FT-IR (neat): 699, 749, 799, 1012, 1092, 1208, 1389, 1454, 1495,
1529, 1667, 1739, 1783, 1813, 2862, 3346 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.51-7.42 (m, 8 H), 7.41-7.29 (m, 12 H), 6.83-6.73 (m, 1 H), 5.48 (s, 4 H),
4.40-4.22 (m, 8 H), 4.19-4.08 (m, 1 H), 4.04-3.85 (m, 8 H), 3.82-3.46 (m, 14 H), 3.35-3.21
(m, 4 H), 2.71 (s, 4 H), 2.45 (t, 2 H, J = 8.0 Hz), 2.06 (t, 2 H, J = 8 Hz), 1.83 (quin, 2 H, J = 8.0 Hz). 13C NMR (75 MHz, CDCl3): δ = 171.4 (C), 169.5 (C), 168.1 (C), 138.1 (4 × C), 128.6 (4 × CH), 127.9 (8 ×
CH), 125.9 (8 × CH), 100.9, 100.8 (4 × CH), 78.6 (2 × CH), 71.1, 71.0 (4 × CH), 69.0,
68.9, 68.6, 68.5 (8 × CH2), 67.9 (2 × CH2), 49.4 (CH), 34.1 (CH2), 29.8 (CH2), 25.4 (2 × CH2), 20.3 (CH2). HRMS-FAB: m/z calcd for C58H71N2O19 [M + H]+: 1099.4633; found: 199.4651.
<A NAME="RU05007ST-17">17</A>
Nemoto H,
Yamasaki M,
Suzawa T, and
Yamaguchi H. inventors; WO 2004029018. BGL modification of a protein:
<A NAME="RU05007ST-18">18</A>
Nemoto H,
Yamauchi M,
Kusano H,
Kato Y,
Yamasaki M, and
Suzawa T. inventors; WO 2005023844. BGL modification of a liposome:
<A NAME="RU05007ST-19">19</A>
Abrams MJ,
Bridger GJ,
Schwartz DA,
Padmanabhan S, and
Ultee ME. inventors; WO 9410149.
