3P133

NMR-2JCH ࢆ⏝࠸ࡓ⢾ࡢ㓄ᗙゎᯒ࡟࠾ࡅࡿ⌮ㄽィ⟬ᡭἲࡢ᳨ウ㸦1 ㇏ᶫᢏ⛉኱㝔ᕤࠊ2 ᶓ὾ᕷ኱⏕࿨ࢼࣀࢩࢫࢸ࣒㸧‫ۑ‬ᯇཎ ṇ㝧 1ࠊཬᕝ 㞞ே 2ࠊᚋ⸨ ோᚿ 1࠙⥴ゝࠚ⢾ࢱࣥࣃࢡ㉁ࡸ⢾⬡㉁࡜ࡋ࡚Ꮡᅾࡍࡿ⢾㙐ࡣ㸪⏕యෆ࡟࠾࠸࡚ᵝࠎ࡞ᙺ๭ࢆᣢࡗ࡚࠸ࡿ㸬⣽⬊ୖࡢ⢾㙐ㄆ㆑ᶵᵓ࡟࠾࠸࡚ࡣ⢾㙐㓄ิࡢഹ࠿࡞㐪࠸ࡀุูࡉࢀ࡚࠾ࡾ㸪ࡑࡢᶵ⬟ࡣ༢࡟ྛ⢾ṧᇶࡢ⎔ࡢᏳᐃ࡞㓄ᗙࡔࡅ࡛ㄝ࡛᫂ࡁࡿ࡜ࡣ㝈ࡽ࡞࠸㸬ࡑࡇ࡛㸪භဨ⎔ୖࡢỈ㓟ᇶࡢ㓄ྥࡸ⢾㙐ṧᇶ㛫ࡢỈ⣲⤖ྜᵓ㐀ࢆ᫂ࡽ࠿࡟ࡍࡿẚ㍑ⓗ⡆༢࡞ゎᯒᡭἲࡢ☜❧ࡀᮃࡲࢀ࡚࠸ࡿ㸬୍⯡࡟⢾ࡢ❧య㓄ᗙゎᯒ࡟ࡣ NMR ἲࡀ⏝࠸ࡽࢀ㸪≉࡟ཬᕝ➼ࡣ❧యᵓ㐀࡟㉳ᅉࡍࡿ᝟ሗࡢ୍ࡘ࡛࠶
ࡿ 2 ⤖ྜ 13C-1H ࢫࣆࣥ-ࢫࣆࣥ⤖ྜᐃᩘ㸦2JCH㸧ࡀࡑࡢ⤌ࡳྜࢃࡏ࠿ࡽ≉ᐃࡢ⢾ࢆྠᐃ࡛ࡁࡿࡇ࡜ࢆ♧ࡋOH OH
ࡓ[1]㸬ࡲࡓ㸪NMR-2JCH ್ࡣ㛵㐃ࡍࡿ⨨᥮ᇶࡢ㓄ྥ࡟ᙉࡃ౫Ꮡࡋ࡚࠸ࡿࡇ࡜
6ࡀ⌮ㄽィ⟬࠿ࡽ᫂ࡽ࠿࡟ࡉࢀࡘࡘ࠶ࡿ[2]㸬ࡑࡇ࡛㸪 NMR-3JHH ್࡟ຍ࠼࡚
45 H O
NMR-2JCH ್ࢆ⏝࠸ࢀࡤ㸪⢾ࡢ⎔㓄ᗙࡔࡅ࡛࡞ࡃ㞄᥋ࡍࡿỈ㓟ᇶࡢྥࡁࡸ㛵㐃 H231 HHOࡍࡿࡡࡌࢀゅࢆほ ࡍࡿࡇ࡜ࡶྍ⬟࡜࡞ࡿࡓࡵ㸪⢾ࡸ⢾㙐ࡀ㛵ࢃࡿ⏕⌮άᛶHOH࡟┤⤖ࡍࡿゎᯒᡭἲࡢ☜❧ࡀᮇᚅ࡛ࡁࡿ㸬ࡑࡇ࡛ᡃࠎࡣ㸪NMR-2JCH ࢆ⨨᥮ᇶ
HOHࡢ❧యᵓ㐀࡟㛵ಀ࡙ࡅࡓ Karplus ᘧࡢࡼ࠺࡞⤒㦂ⓗ㛵ಀᘧࢆ᳨ウࡍࡿࡓࡵ㸪
αα-Gal࢞ࣛࢡࢺ࣮ࢫ㸦α-Gal㸧ࢆᡭጞࡵ࡟㸪⌮ㄽィ⟬࡟ᇶ࡙࠸࡚ᵝࠎ࡞⢾࡟ᑐࡍࡿ❧య㓄ᗙゎᯒࢆ⾜ࡗ࡚࠸ࡿ㸬௒ᅇࡢ◊✲࡛ࡣ㸪㓄ᗙ᥈⣴ࣉࣟࢢ࣒ࣛ CONFLEX6[3]࡟ࡼࡿ α-Gal ࡢ㓄ᗙ᥈⣴ࡢ⤖ᯝᚓࡽࢀࡓ࠸ࡃࡘ࠿ࡢ㓄ᗙ␗ᛶయ࡟ᑐࡋ࡚ Gaussian03[4]࡟ࡼࡿ NMR ィ⟬ࢆ㐺⏝ࡋ㸪⌮ㄽィ⟬࡜㓄ᗙゎᯒ࠿ࡽᑟ࠿ࢀࡓ⤖ྜᐃᩘ J ್ࢆᐇ㦂್࡜ẚ㍑ࡍࡿࡇ࡜࡟ࡼࡗ࡚㸪⌮ㄽィ⟬ࡢ⢭ᗘࢆ᳨ドࡍࡿ࡜࡜ࡶ࡟㸪Ỉ⁐ᾮ୰࡛ඃ఩࡟Ꮡᅾࡍࡿ⢾ࡢヲ⣽࡞❧య㓄ᗙゎᯒࢆヨࡳࡿ㸬ࡲࡓ㸪β-ࢢࣝࢥ࣮ࢫ㸦β-Glc㸧㸪β-࣐ࣥࣀ࣮ࢫ㸦β-Man㸧࡟ᑐࡋ࡚ࡶྠᵝࡢ᳨ドࢆ⾜࠺㸬࠙᪉ἲࠚ
CONFLEX/MMFF94s[2]࡟ࡼࡗ࡚ᚓࡽࢀࡓ α-Gal ࡢᏳᐃ࡞㓄ᗙ␗ᛶయ࡟ᑐࡋ㸪Gaussian03 ࢆ⏝࠸࡚ᐦᗘỗ㛵ᩘ⌮ㄽ㸦DFT㸧ἲࢆ⏝࠸࡚ᵓ㐀᭱㐺໬ࢆ⾜࠸㸪ࡑࡢ᭱㐺໬ᵓ㐀࡟ᑐࡋ࡚ NMR ⌮ㄽィ⟬ࢆ⾜ࡗࡓ㸬ࡇࡇ࡛㸪NMR ⌮ㄽィ⟬ࡣ㐺⏝ࡋࡓ DFT ἲ࡟ࡼࡗ࡚ண ⢭ᗘࡸィ⟬᫬㛫ࡀ␗࡞ࡿࡓࡵ㸪࠸ࡃࡘ࠿ࡢᇶᗏ㛵ᩘ࡜ DFT ἲࡢ⤌ࡳྜࢃࡏ࡛ᵓ㐀᭱㐺໬࡜ NMR ⌮ㄽィ⟬ࢆ⾜ࡗࡓ㸬ࡑࡢ⤖ᯝ㸪B3PW91/6-311+G(2d,p)//B3PW91/6-31+G**ࡀẚ㍑ⓗຠ⋡ࡼࡃ㧗࠸⢭ᗘ࡛ NMR-2JCH ࢆண ࡍࡿࡇ࡜ࡀ࡛ࡁࡓ㸬ࡇࡢ⤖ᯝ࡟ᚑࡗ࡚㸪
CONFLEX ࡛ᚓࡽࢀࡓᏳᐃ࡞ 20 ✀㢮ࡢ㓄ᗙ࡟ࡘ࠸࡚㸪ࡇࡢ⤌ࡳྜࢃࡏࢆ౑ࡗ࡚ᵓ㐀᭱㐺໬ࢆ⾜࠸㸪J ್ࢆồࡵࡓ㸬ࡲࡓ㸪Ẽ┦ࣔࢹࣝ࡟ຍ࠼࡚㸪Ỉ⁐ᾮࣔࢹࣝ࡜ࡋ࡚ IEF-PCM㸦PCM㸧࡜ Isodensity PCM㸦IPCM㸧ࣔࢹࣝ࡟ࡼࡿィ⟬ࢆ⾜ࡗࡓ㸬ࡲࡓ㸪β-Glc ࡜ β-Man ࡢ㓄ᗙ␗ᛶయ࡟ࡘ࠸࡚ࡶ㸪ྠᵝ࡞ゎᯒࢆ⾜ࡗࡓ㸬
NMR-2JCH㸪3JHH ್ࡢᐇ㦂್࡜⌮ㄽ್ࢆẚ㍑ࡍࡿࡓࡵ㸪Ẽ┦ࣔࢹࣝ࡜Ỉ⁐ᾮࣔࢹࣝࡢࡑࢀࡒࢀࡢྛ㓄ᗙ␗ᛶయࡢ㓄ᗙ࢚ࢿࣝࢠ࣮࠿ࡽ࣎ࣝࢶ࣐ࣥศᕸഃ࡟ᇶ࡙ࡃᏑᅾẚࢆồࡵ㸪ࡑࡢᏑᅾẚ࡛㔜ࡳ௜ࡅࡋࡓ J ್ࡢ⌮ㄽᖹᆒ್ࢆồࡵࡓ㸬ࡲࡓ㸪ࡼࡾ㧗࢚ࢿࣝࢠ࣮㡿ᇦ࡟࠶ࡿ㓄ᗙ␗ᛶయ࡟ࡘ࠸࡚㸪ࡼࡾᐇ㦂್ࢆ෌⌧࡛ࡁࡿ❧యᵓ㐀ࢆ᳨ウࡋࡓ㸬࠙⤖ᯝ࡜⪃ᐹࠚα-Gal ࡢ 20 ✀㢮ࡢ㓄ᗙ␗ᛶయ࡟ࡘ࠸࡚㸪Ỉ⁐ᾮࣔࢹࣝ࡟ࡼࡿ DFT ィ⟬ࢆ⾜࠸㸪ࡑࢀࡽࡢྛ㓄ᗙ࢚ࢿࣝࢠ࣮ࢆ⏝࠸࡚࣎ࣝࢶ࣐ࣥศᕸഃ࡟ᇶ࡙ࡃ NMR-2JCH ࡜ 3JHH ್ࡢ⌮ㄽᖹᆒ್ࢆồࡵࡓ㸬ࡑࡢ⤖ᯝ㸪ᐇ㦂್࡟ᑐࡍࡿ RMSD ࡣࡑࢀࡒࢀ 1.5Hz ࡜ 1.2Hz C1,H2
࡛࠶ࡗࡓ㸦Fig.1㸧㸬ࡇࡢ⤖ᯝࡣ㸪Ẽ┦୰ࡢከ C2,H1㓄ᗙゎᯒ࡟ࡼࡿ⌮ㄽᖹᆒ್ࡸ㸪Ỉ⁐ᾮࣔࢹࣝ C2,H3
࡟࠾ࡅࡿ᭱Ᏻᐃ㓄ᗙࡼࡾࡶᐇ㦂್ࢆ෌⌧ࡋࡓ㸬 C3,H2
2
JC4,H5 C3,H4
࡜ࡇࢁࡀ㸪
Fig. 1 ࡼࡾ᫂ࡽ࠿࡞ࡼ࠺࡟㸪3
࡜ JH2,H3 ࡔࡅࡀ㸪ᐇ㦂್࡜኱ࡁࡃ␗࡞ࡾ㸪ࡑ C4,H3
ࡢᕪࡣ 2~3 Hz ࡛࠶ࡗࡓ㸬ࡑࡇ࡛ 20 ✀㢮ࡢ㓄 C4,H5
ᗙ␗ᛶయࡢ J ್࡜❧యᵓ㐀ࡢ㛵ಀࢆヲ⣽࡟ㄪ C5,H4
࡭ࡓ࡜ࡇࢁ㸪MMFF94s ࡟࠾࠸࡚ 13 ␒┠࡟Ᏻ
-4.0

in vacuoin water(IPCM)

in water(PCM)
in water(IPCM)

H2,H3
H3,H4
H4,H5-4.0 -2.00.0

Δ3JHH

2.0

4.0Fig.1 Differences between experimental
-2.0

0.0

2.0

Δ2JCH
2in vacuo

H1,H2in water(PCM)

4.0

and theoretical 2JCH and 3JHH values(ΔJ =J(calc.)-J(expl.))3

Table.1 Experimental and theoretical JCH and JHH values for α-Gal conformers in higher energy region
in vacuoExpl.
averagein water

DEDEkcal/mol kcal/mol-------

23J C,HJ H,HC1,H2 C2,H1 C2,H3 C3,H2 C3,H4 C4,H3 C4,H5 C5,H4 RMSD H1,H2 H2,H3 H3,H4 H4,H5 RMSD
-0.4 -1.0 -5.4 -6.2 -4.6
1.2
5.6
1.5
4.0 10.3
3.4
1.0-

*1

-----1.7 -1.5 -3.5 -4.8 -4.1
0.8
2.7
3.74
3.55
-1.5 -0.3 -4.8 -3.4 -5.1
0.7
4.8
3.14
2.50
-1.6 -1.6 -4.6 -4.8 -5.0
0.5
4.8
*1 average of 20 conformers in water (using PCM) based on Boltzmann distribution law

4C1 cccc tg t
4
C1 rrcc tg g-0.7
1.6
1.5

1.46
1.18
0.84

4.0
3.4
3.9

8.0
8.0
8.6

3.2
3.8
3.7

4

1.7
1.51.51.20
1.250.91ᐃ࡞㓄ᗙ㸦 C1 cccc tg t; Fig.2 ᕥ㸧ࡢࡼ࠺࡟㸪O6 ࡀ O5 ࡟ᑐࡋ࡚ trans㸪
C4 ࡟ᑐࡋ࡚ gauche㸦tg㸧㸪࠾ࡼࡧ 4㸫OH ࡀ⎔࡟ᑐࡋ࡚እഃ࡟ྥࡃ
㸦clockwise: c㸧᫬࡟ 2JC4,H5 ್ࡀᐇ㦂್࡟㏆࡙ࡃࡇ࡜ࡀศ࠿ࡗࡓ㸬ࡑࡇ࡛㸪ࡇࢀࡽ࡜ྠࡌᵓ㐀ࢆᣢࡘ㓄ᗙ␗ᛶయࢆ MMFF94s ࡢ㧗࢚ࢿࣝࢠ࣮㡿ᇦ࠿ࡽ㑅ᢥࡋ㸪ྠᵝ࡞ィ⟬ࢆ㐺⏝ࡋࡓ࡜ࡇࢁ㸪2JC4,H5 ࡢᐇ㦂
4
4
C1 rrcc tg g
C1 cccc tg t್ࢆ෌⌧࡛ࡁࡿ㓄ᗙࡀ࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓ㸬≉࡟㸪MMFF94s ࡛ 77
Fig.2 α-Gal conformers which 2JCH4␒┠ࡢ㓄ᗙ␗ᛶయ㸦 C1 rrcc tg g : Fig.2 ྑ㸧࡟࠾࠸࡚㸪NMR-2JCH ࡜
close in value to experimental
3JHH ࡢᐇ㦂್࡟ᑐࡍࡿ RMSD ࡣࡑࢀࡒࢀ 1 Hz ௨ୗ࡛࠶ࡗࡓ
㸦Table.1㸧㸬ࡋ࠿ࡋ㸪࡝ࡢ⤌ࡳྜࢃࡏ࡛㐺⏝ࡋ࡚ࡶ㸪ࡑࡢ㓄ᗙ࢚ࢿࣝࢠ࣮ࡀ 2.50 kcal/mol ௨ୗ࡟࡞ࡿࡇ࡜ࡣ࡞ࡃ㸪J ್ࡢ⌮ㄽᖹᆒ್࡟᭷ព࡟ᐤ୚ࡍࡿࡇ࡜ࡣ࡞࠿ࡗࡓ㸬ࡑࡢ❧యᵓ㐀ࡣ㸪Fig. 2 ྑ࡟♧ࡋࡓࡼ࠺࡟㸪ࡍ࡭࡚ࡢỈ㓟ᇶࡀ⎔࡟ᑐࡋ࡚እഃࢆྥ࠸࡚࠸ࡿࡓࡵ㸪ศᏊෆ࡛ᙉ࠸Ỉ⣲⤖ྜࢆᙧᡂࡋ࡚࠸࡞࠸㸬ࡘࡲࡾ㸪NMR ⌮ㄽィ⟬ࡀࡇࡢ㓄ᗙࡢ❧యᵓ㐀࡟ᑐࡋ࡚༑ศ࡟㧗࠸⢭ᗘ࡛ࡑࡢ J ್ࢆ෌⌧࡛ࡁ࡚࠸ࡿ࡜ࡍࢀࡤ㸪
NMR ࡛ほ ࡋ࡚࠸ࡿ J ್࡟ᑐࡍࡿࡇࡢ㓄ᗙࡢᐤ୚ࡣ኱ࡁ࠸ࡣࡎ࡛࠶ࡾ㸪ࡑࢀࡣ㸪⢾ࡢỈ㓟ᇶ࡟⁐፹࡜ࡋ࡚㓄఩ࡋࡓỈศᏊ࡜ࡢ㛫ࡢỈ⣲⤖ྜࡢᙧᡂ࡟ࡼࡗ࡚኱ࡁࡃᏳᐃࡋࡓ࡜⪃࠼࡚ࡶࡼ࠸ࡔࢁ࠺㸬ࡇࡢࡇ࡜࠿ࡽ㸪፹య㏆ఝ࡟ᇶ࡙ࡃ⁐፹ຠᯝࢆ⪃៖ࡋࡓ⌮ㄽィ⟬࡟࠾࠸࡚㸪ศᏊෆỈ⣲⤖ྜ࡟ᑐࡋ࡚⁐፹࡜ࡢศᏊ㛫Ỉ⣲⤖ྜࡣ㐣ᑠホ౯ࡉࢀ࡚࠸ࡿ࡜ゝ࠼ࡿ㸬ࡲࡓ㸪ࡇࡢၥ㢟ࢆ㑊ࡅࡿ࡟ࡣ㸪౛࠼ࡤ㸪᫂♧ⓗ࡟ỈศᏊࢆ㓄఩ࡉࡏࡿ᪉ἲ[5]ࡀ⪃࠼ࡽࢀࡿࡀ㸪ỈศᏊࡢ㓄⨨࡟ᑐࡍࡿ௵ពᛶࡣ㑊ࡅࡿࡇ࡜ࡣ࡛ࡁ࡞࠸ࡋ㸪ࡲࡓࡇࡢࢣ࣮ࢫ࡜ࡣ㏫࡟㸪ศᏊෆỈ⣲⤖ྜࡀඃ఩࡞㓄ᗙࢆṇ☜࡟ホ౯ࡍࡿࡇ࡜ࡀ㞴ࡋࡃ࡞ࡿࡔࢁ࠺㸬β-Glc ࡢ 20 ✀㢮ࡢ㓄ᗙ␗ᛶయ࡟ࡘ࠸࡚ྠᵝࡢィ⟬ࢆ⾜ࡗࡓ࡜ࡇࢁ㸪Ỉ⁐ᾮ୰࡛ࡢ NMR-2JCH ࡜ 3JHH ್ࡢ⌮ㄽᖹᆒ್ࡣ㸪ᐇ㦂್࡟ᑐࡍࡿ RMSD ࡛㸪ࡑࢀࡒࢀ 1.0Hz ࡜ 2.1Hz ࡛࠶ࡗࡓ㸬ࡇࢀࡶ α-Gal ࡜ྠᵝ࡟㸪Ỉ⁐ᾮࣔࢹࣝ࡟࠾ࡅࡿከ㓄ᗙゎᯒ࡟ࡼࡗ࡚ᐇ㦂್࡟㏆࡙ࡃࡶࡢࡢ㸪࠸ࡃࡘ࠿ࡢ J ್ࡣ 2Hz ௨ୖࡶᐇ㦂್࡜␗࡞ࡗ࡚࠸ࡓ㸬β-Man ࡟ࡘ࠸࡚ࡶ㸪⌧ᅾゎᯒ୰࡛ࡣ࠶ࡿࡀ㸪ྠᵝࡢഴྥࡀぢࡽࢀࡿ㸬ཧ⪃ᩥ⊩[1] M. Oikawa, S. Adachi, S. Kusumoto, Organic Lett., 2005, 7; 661-664.
[2] Thomas E. Klepach, Ian Carmichael, and Anthony S. Serianni, J. Am. Chem. Soc. 2005, 127; 9781-9793[3] CONFLEX6, H. Goto, S. Obata, T. Kamakura, N. Nakayama, K. Ohta; Conflex Corp., Tokyo, 2006.
[4] Gaussian 03, Revision E.01, M. J. Frisch, et. al., Gaussian, Inc., Wallingford CT, 2004.
[5] F. A. Momany, M. Appell, G. Strati, J. L. Willett, Carbohydr. Res. 2005, 340; 1638-1655