薬学基礎実習Ⅰ- ２カフェインとCompound Aスペクトルによる構造解析

N

N N

NO

O

H3C

CH3

CH3

N

N N

NO

O

CH3H3C

CH3

カフェイン

1H,13C-NMRの化学シフトをHSQC, HMBCにより帰属原植物名

コーヒーノキ アカネ科Coffea arabica

焙煎 粉砕

EI-MS Spectrum of caffeine 194(M+)

109165

826755

下記スペクトルデータを用い、caffeineの1H-NMR,13C-NMR および15N-NMRの化学シフト値を帰属しなさい。

35.0 40.0 45.0 50.0 55.0 60.0 65.0 70.0 75.0 80.0 85.0 90.0 95.0 100.0 105.0 110.0 115.0 120.0 125.0 130.0 135.0 140.0 145.0 150.0 155.0 160.0 165.0 170.0 175.0 180.0 185.0 190.0 195.0 m/z0.00

0.25

0.50

0.75

1.00

Inten.(x10,000)

N

N N

NO

O

CH3H3C

CH3

CaffeineMolecular formula: C8H10N4O2Molecular weight: 194

1H-NMR Spectrum of caffeine (600MHz, CDCl3, 298K)

3.40(3H, s)

CHCl3

7.50(1H, s)

3.57(3H, s)

3.98(3H, s)

13C-NMR Spectrum of caffeine (150MHz, CDCl3, 298K)

27.9(q)

CDCl3

29.7(q)33.6(q)

107.6(s)

141.4(d)

148.7(s)

155.4(s)

151.7(s)

Homo-nuclear Correlation Spectroscopy

1H-1H COSY, DQF-COSY, MQ-COSY

C C

Ha Hb

3JHa-Hb

1H

1H

Ha

Ha

Hb

Hb

13C-13C INADEQUATE

C3 C1 C2

Ha

C4

Hb

1JC1-C3

13C

C1C2

O

C3 C4

1JC1-C2

1JC2-C4

Hetero-nuclear Correlation Spectroscopy

1H-13C COSY, HMQC,HSQC, HETCOR

C1 C2

Ha Hb

1JC1-Ha

1H

13C

Ha

Hb

1JC2-Hb

C1C2

1H-13C Longrange, HMBC, COLOC

C1 C2

Ha

C3

3JC3-Ha

1H

13C

Ha

OC3

1JC1-Ha 120-140Hz

C1C2

HSQC Spectrum of caffeine (600MHz, CDCl3, 298K)

HMBC Spectrum of caffeine (600MHz, CDCl3, 298K)

1H-15N HMBC Spectrum of caffeine (600MHz, CDCl3, 298K)

-266.8

15N

-229.7

-225.8

-151.2

N

N N

NO

O

CH3H3C

CH3

1

2 34

56 7

8

9

カフェインのNMRスペクトル帰属

No 1H 13C 15N

1 N-CH3

2

3 N-CH3

4

5

6

7 N-CH3

8 7.50(1H,s) 141.4(d)

9 N

EI-MS Spectrum of Compound A

208(M+)163(base peak)

180

145

136

117

89

コーヒーに含まれる成分の誘導体（Compound A）の構造を、下記スペクトルデータを用い決定し、1H-NMRおよび13C-NMRの化学シフト値を帰属しなさい。

1H-NMR Spectra of Compound A (600MHz, dmso-d6, 298K)

Ha: 1.21(3H, t, J=7.2Hz)

solvent

enlarged

Hb: 4.12(2H, q, J=7.2Hz)

Hc: 6.23(1H, d, J=15.6Hz)Hd: 6.74(1H, d, J=8.4Hz)

He: 6.97(1H, dd, J=2.0, 8.4Hz)

Hf: 7.02(1H, d, J=2.0Hz)Hg: 7.44(1H, d, J=15.6Hz)

13C-NMR Spectra of Compound A (150MHz, dmso-d6, 298K)

C1:14.7(q)solvent

enlarged

C2:60.2(t)

C3:115.1(d)C4:115.5(d)

C5:116.2(d)C6:121.6(d)

C7:126.1 (s)C8:145.0 (d)

C9:146.0 (s)C10:148.6 (s)

C11:168.3 (s)

HSQC Spectrum of Compound A (600MHz, dmso-d6, 298K)

HSQC Spectrum of Compound A _enlarged (600MHz, dmso-d6, 298K)

HMBC Spectrum of Compound A (600MHz, dmso-d6, 298K)

HMBC Spectrum of Compound A_enlarged (600MHz, dmso-d6, 298K)

1H-1H COSY Spectrum of Compound A (600MHz, dmso-d6, 298K)

1H-1H COSY Spectrum of Compound A_enlarged (600MHz, dmso-d6, 298K)

3JH-H と3JC-Hについて

C C

H H

C

H H

vicinal geminal

3JH-H2JH-H

C

H

1JC-H

C C

H

3JC-H

CXJ=120-140Hz

J=5-10Hz

2JC-H J=-4.4Hz

C C

H H

Z (cis): J=6-12Hz

3JH-H

C C

H

HE (trans): J=12-18Hz

3JH-H

HH

3JH-H

ortho: J=6-10Hz

H

4JH-H

meta: J=1-3HzH

H

5JH-H

meta: J=0-1HzH

CH

1JC-H

J=158Hz

C

H

2JC-H

J=1.1Hz

C

H

3JC-H

J=7.6HzC

H

4JC-H

J=-1.2Hz

1H-1H COSY HSQC HMBC

1H-NMR

1H-NMR

HMBC

HSQC

二重結合の幾何異性？

？置換ベンゼン

？ベンゼン環の置換基