Arch. Pharm. Chem. Life Sci. 2007, 340, 625–634
Agelasine Analogs from b-Cyclocitral
631
matography on silica gel eluting with CH2Cl2/MeOH sat. with
NH3 (12 : 1); yield 12b 107 mg (80%). The fractions containing iso-
mer 13b were combined, evaporated, and purified by flash chro-
matography eluting with hexane-EtOAc (1 : 1); yield 13b 7 mg
(7%).
7.31–7.37 (m, 2H, Ph), 7.80 (s, 1H, H-2), 8.28 (s, 1H, H-8); 13C-NMR
(CDCl3, 75 MHz) d 16.1 (CH3), 16.8 (CH3), 19.5 (CH2), 19.8 (CH3),
26.3 (CH2), 27.9 (CH2), 28.6 (26CH3), 31.0 (NCH3), 32.7 (CH2), 35.0
(C-6 in cyclohexene), 39.5 (CH2), 39.8 (CH2), 40.4 (CH2), 47.6
(NCH2), 75.7 (OCH2), 109.8 (C-5), 116.0 (CH=), 122.7 (CH=), 127.1
(C=), 127.1 (CH in Ph), 127.9 (26CH in Ph), 128.4 (26CH in Ph),
129.9 (C-8), 136.9 (C=), 137.0 (C=), 139.3 (C in Ph), 144.7 (C-4),
145.6 (C=), 146.4 (C-6), 156.1 (C-2); HRMS (ESI) Found 528.3687,
C33H45N5O+H requires 528.3696.
12b
Mp 160–1628C, pale yellow crystals. 1H-NMR (CDCl3, 300 MHz) d
0.95 (s, 6H, 26CH3), 1.27 (s, 9H, t-Bu), 1.37–1.40 (m, 2H, CH2),
1.49-1.53 (m, 2H, CH2), 1.56 (s, 3H, CH3), 1.61 (s, 3H, CH3), 1.82 (s,
3H, CH3), 1.89 (t, J = 5.7 Hz, 2H, CH2), 1.95–2.13 (m, 8H, 46CH2,),
3.84 (s, 3H, NCH3), 5.07–5.10 (m, 3H, NCH2 and CH=), 5.53 (t, J =
6.9 Hz, 1H, CH=), 7.83 (s, 1H, H-2), 8.99 (s, 1H, H-8); 13C-NMR
(CDCl3, 75 MHz) d 16.1 (CH3), 17.1 (CH3), 19.5 (CH2), 19.8 (CH3),
26.1 (CH2), 27.6 (36CH3 in t-Bu), 27.9 (CH2), 28.6 (26CH3), 31.4
(NCH3), 32.7 (CH2), 34.9 (C-6 in cyclohexene), 39.5 (CH2), 39.8
(CH2), 40.3 (CH2), 47.8 (NCH2), 77.8 (C in t-Bu), 110.9 (C-5), 116.0
(CH=), 122.7 (CH=), 127.0 (C=), 131.8 (C-8), 136.9 (C=), 137.0 (C=),
142.2 (C-6), 143.7 (C-4), 145.5 (C=), 154.3 (C-2); HRMS (ESI) Found
494.3836, C30H47N5O+H requires 494.3853.
13c
1
Colorless oil. H-NMR (CDCl3, 300 MHz) d 0.96 (s, 6H, 26CH3),
1.36–1.40 (m, 2H, CH2), 1.49–1.58 (m, 2H, CH2), 1.55 (s, 3H, CH3),
1.57 (s, 3H, CH3), 1.70 (s, 3H, CH3), 1.87 (t, J = 6.2 Hz, 2H, CH2),
1.95–2.06 (m, 8H, 46CH2), 3.82 (s, 3H, NCH3), 4.65 (d, J = 6.9 Hz,
2H, NCH2), 5.07 (t, J = 6.3 Hz, 1H, CH=), 5.14 (s, 2H, OCH2), 5.41 (t, J
= 6.8 Hz, 1H, CH=), 7.15–7.37 (m, 3H, Ph), 7.54–7.57 (m, 2H, Ph),
7.80 (s, 1H, H-2), 8.49 (s, 1H, H-8); 13C-NMR (CDCl3, 75 MHz) d 16.0
(CH3), 16.6 (CH3), 19.5 (C-4 in cyclohexene), 19.8 (CH3), 26.4 (CH2),
27.9 (CH2), 28.6 (26CH3), 29.7 (NCH3), 32.7 (CH2), 34.9 (C-6 in
cyclohexene), 39.7 (CH2), 39.8 (CH2), 40.2 (CH2), 49.4 (CH2), 77.3
(OCH2), 118.4 (CH=), 119.4 (C-5), 123.3 (CH=), 126.8 (C=), 128.3
(26CH in Ph), 128.4 (CH in Ph), 129.7 (26CH in Ph), 136.0 (C in
Ph), 136.2 (C=), 137.1 (C=), 140.3 (C=), 140.9 (C-8), 151.7 (C-4),
152.2 (C-2), 165.5 (C-6); MS EI m/z (rel.%) 527 (4) [M+], 216 (100),
150 (32), 149 (53), 107 (40), 105 (33), 95 (34); HRMS (EI) Found
527.3612, C33H45N5O requires 527.3624.
13b
1
Colorless oil. H-NMR (CDCl3, 300 MHz) d 0.94 (s, 6H, 26CH3),
1.35–1.39 (m, 2H, CH2), 1.36 (s, 9H, t-Bu), 1.49–1.57 (m, 2H, CH2),
1.53 (s, 3H, CH3), 1.54 (s, 3H, CH3), 1.66 (s, 3H, CH3), 1.86 (t, J =
6.4 Hz, 2H, CH2), 1.87–1.98 (m, 8H, 46CH2), 3.80 (s, 3H, NCH3),
4.22 (br s, 1H, Ha in NCH2), 5.00 (t, J = 6.4 Hz, 1H, CH=), 5.51 (t, J =
6.3 Hz, 1H, CH=), 5.40 (br s, 1H, Hb in NCH2), 7.77 (s, 1H, H-2), 8.49
(s, 1H, H-8); 13C-NMR (CDCl3, 75 Hz) d 15.9 (CH3), 16.6 (CH3), 19.5
(CH2), 19.8 (CH3), 26.4 (CH2), 27.2 (36CH3 in t-Bu), 27.9 (CH2), 28.6
(2 ' CH3), 29.7 (NCH3), 32.7 (CH2), 34.9 (C-6 in cyclohexene), 39.6
(CH2), 39.8 (CH2), 40.2 (CH2), 53.7 (NCH2), 82.3 (C in t-Bu), 118.9
(CH=), 120.1 (C-5), 123.4 (CH=), 126.8 (C=), 136.0 (C=), 137.2 (C=),
139.5 (C=), 140.5 (C-8), 151.6 (C-4), 152.0 (C-2), 159.5 (C-6); MS EI
m/z (rel.%) 493 (1), [M+], 437 (21), 216 (36), 166 (36), 165 (100), 150
(15), 149 (18), 135 (23), 95 (17); HRMS (EI) Found 493.3798,
C30H47N5O requires 493.3781.
(29E,69E)-6-Amino-9-methyl-7-[3,7-dimethyl-9-(2,6,6-
trimethylcyclohex-1-enyl)nona-2,6-dien-1-yl]-7H-
purinium chloride 14
A mixture of betaine 12b (165 mg, 0.33 mmol), Zn (272 mg,
4.16 mmol), and AcOH (0.33 mL) in MeOH (17 mL) and water
(1.7 mL) was stirred vigorously at 758C for 19 h. The mixture was
filtered and the solid washed with MeOH (17 mL). Brine (8.5 mL)
and water (8.5 mL) were added and the mixture was stirred for
1 h at ambient temperature and evaporated in vacuo. The residue
was mixed with brine (35 mL) and CHCl3 (40 mL). The phases
were separated and the aqueous phase was extracted with CHCl3
(3640 mL). The combined organic layers were dried (MgSO4),
and evaporated in vacuo. The residue was purified by flash chro-
matography on silica gel eluting with CH2Cl2/MeOH (6:1); yield
106 mg (70%), mp 181–1838C, colorless crystals. 1H-NMR (CDCl3,
300 MHz) d 0.94 (s, 6H, 26CH3), 1.35–1.39 (m, 2H, CH2), 1.44–
1.53 (m, 2H, CH2), 1.55 (s, 3H, CH3), 1.57 (s, 3H, CH3), 1.83 (s, 3H,
CH3), 1.87 (t, J = 5.9 Hz, 2H, CH2), 1.93–2.06 (m, 8H, 46CH2), 4.04
(s, 3H, NCH3), 5.01 (br s, 1H, CH=), 5.44 (t, J = 6.8 Hz, 1H, CH=), 5.69
(d, J = 6.8 Hz, 2H, NCH2), 6.98 (br s, 2H, NH2), 8.44 (s, 1H, H-2),
10.73 (s, 1H, H-8); 13C-NMR (CDCl3, 75 MHz) d 16.1 (CH3), 17.4
(CH3), 19.5 (CH2), 19.8 (CH3), 26.1 (CH2), 27.8 (CH2), 28.6 (26CH3),
31.9 (NCH3), 32.7 (CH2), 34.9 (C-6 in cyclohexene), 39.5 (CH2), 39.8
(CH2), 40.3 (CH2), 48.6 (NCH2), 109.9 (C-5), 115.9 (CH=), 122.4
(CH=), 127.0 (C=), 136.9 (C=), 137.0 (C=), 145.8 (C-8), 146.7 (C=),
149.5 (C-4), 152.4 (C-6), 156.1 (C-2); HRMS (EI) Found 422.3260,
C26H40N5+ requires 422.3278.
7-[(29E,69E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-
enyl)nona-2,6-dien-1-yl]-6-benzyloxyamino-9-methyl-7H-
purinium 12c and N6-[(29E,69E)-3,7-dimethyl-9-(2,6,6-
trimethylcyclohex-1-enyl)nona-2,6-dien-1-yl]-N6-
benzyloxy-9-methyl-9H-purin-6-amine 13c
A
mixture of N6-benzyloxy-9-methyl-9H-purin-6-amine 11c
(69 mg, 0.27 mmol) and allylic bromide 10 (98 mg, 0.32 mmol)
in dry DMA (2.5 mL) was stirred at 508C under N2-atm. for 21 h
and evaporated in vacuo. The residue was purified by flash chro-
matography on silica gel eluting with CH2Cl2/MeOH sat. with
NH3 (12 : 1); yield 12c 100 mg (70%). The fractions containing iso-
mer 13c were combined, evaporated, and purified by flash chro-
matography eluting with hexane-EtOAc (1 : 1); yield 13c 26 mg
(18%).
12c
Mp 158–1608C, pale yellow crystals. 1H-NMR (CDCl3, 300 MHz) d
0.96 (s, 6H, 26CH3), 1.37–1.40 (m, 2H, CH2), 1.50–1.56 (m, 2H,
CH2), 1.57 (s, 3H, CH3), 1.62 (s, 3H, CH3), 1.73 (s, 3H, CH3), 1.88 (t, J
= 6.1 Hz, 2H, CH2), 1.92–2.11 (m, 8H, 46CH2), 3.68 (s, 3H, NCH3),
4.96 (d, J = 7.4 Hz, 2H, NCH2), 5.00 (s, 2H, OCH2), 5.07 (t, J = 6.4 Hz,
1H, CH=), 5.37 (t, J = 6.9 Hz, 1H, CH=), 7.15–7.21 (m, 3H, Ph),
7-[(29E,69E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-
enyl)nona-2,6-dienyl]-3-methyl-3H-purin-6(7H)-imine 16
A solution of the allylic bromide 10 (278 mg, 0.79 mmol) in dry
DMA (2 mL) was added to a stirring solution of 3-methyladenine
i 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim