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A. Srikrishna, P. C. Ravikumar / Tetrahedron Letters 46 (2005) 6105–6109
(1H, dt, J 16.5 and 2.1 Hz), 2.06 (3H, s), 1.48 (3H, s), 1.46
(3H, s), 0.82 (3H, t, J 6.9 Hz); 13C NMR (75 MHz,
CDCl3+CCl4): d 176.4 (C), 157.7 (C), 156.8 (C), 139.6
(CH), 130.9 (CH), 126.6 (CH), 125.0 (C), 116.5 (C), 95.6
(CH), 59.6 (CH2), 58.3 (C), 55.6 (C), 55.2 (CH3), 55.1
(CH3), 46.0 (CH2), 23.5 (CH3), 21.3 (CH3), 15.3 (CH3),
13.6 (CH3); HRMS: m/z calcd for C19H26O4Na (M+Na):
341.1729. Found: 341.1747. 3-Acetyloxy-6-methyl-4-
(1,2,2-trimethylcyclopentyl)phenyl acetate 18: IR (neat):
employed for the construction of cyclopentanes contain-
ing two vicinal quaternary carbon atoms. Extension of
this methodology for the synthesis of HM-3, HM-4
and oxygenated lagopodin analogues, for evaluating
their biological potential, is currently in progress.
Acknowledgement
m
max/cmꢀ1 1764; 1H NMR (300 MHz, CDCl3): d 7.21 (1H,
We thank the Council of Scientific and Industrial
Research, New Delhi for the award of a research fellow-
ship to P.C.R.
s), 6.67 (1H, s), 2.60–2.47 (1H, m), 2.27 (3H, s), 2.26 (3H,
s), 2.14 (3H, s), 1.80–1.47 (5H, m), 1.28 (3H, s), 1.13
(3H, s), 0.73 (3H, s); 13C NMR (75 MHz, CDCl3): d 168.7
(C), 168.0 (C), 147.3 (C), 147.1 (C), 135.8 (C), 131.3 (CH),
126.2 (C), 117.8 (CH), 50.9 (C), 45.3 (C), 40.5 (CH2), 38.9
(CH2), 26.7 (CH3), 25.2 (CH3), 23.4 (CH3), 21.8 (CH3),
20.8 (CH3), 20.2 (CH2), 16.4 (CH3); Mass: m/z 318 (M+,
12%), 276 (40), 234 (65), 219 (12), 206 (18), 193 (11), 177
(21), 164 (100), 151 (67), 137 (11), 110 (23); HRMS: m/z
calcd for C19H26O4Na (M+Na): 341.1729. Found:
341.1730. 5-Acetyloxy-4-methyl-2-(1,2,2-trimethylcyclo-
pentyl)phenol 19: IR (neat): mmax/cmꢀ1 3336, 1721, 1609,
1515; 1H NMR (300 MHz, CDCl3): d 7.10 (1H, s), 6.41
(1H, s), 4.91 (1H, s), 2.62–2.51 (1H, m), 2.29 (3H, s), 2.08
(3H, s), 1.82–1.45 (5H, m), 1.38 (3H, s), 1.16 (3H, s), 0.75
(3H, s); 13C NMR (75 MHz, CDCl3): d 169.3 (C), 153.0
(C), 147.2 (C), 131.5 (CH), 131.2 (C), 120.4 (C), 110.2
(CH), 50.7 (C), 44.7 (C), 41.1 (CH2), 39.5 (CH2), 26.9
(CH3), 25.5 (CH3), 22.8 (CH3), 20.9 (CH3), 20.3(CH2),
15.7 (CH3). 5-Acetyloxy-2-methyl-4-(1,2,2-trimethylcycl-
opentyl)phenol 20: IR (neat): mmax/cmꢀ1 3293, 1723; 1H
NMR (300 MHz, CDCl3): d 7.14 (1H, s), 6.40 (1H, s), 4.92
(1H, br s), 2.60–2.45 (1H, m), 2.29 (3H, s), 2.19 (3H, s),
1.82–1.45 (5H, m), 1.26 (3H, s), 1.11 (3H, s), 0.71 (3H, s);
13C NMR (75 MHz, CDCl3): d 170.2 (C), 151.9 (C), 147.4
(C), 131.6 (CH), 130.1 (C), 120.8 (C), 110.4 (CH), 50.4 (C),
45.1 (C), 40.2 (CH2), 38.7 (CH2), 26.4 (CH3), 24.9 (CH3),
23.4 (CH3), 21.8 (CH3), 20.0 (CH2), 15.7 (CH3). 5-Methyl-
2-(1,2,2-trimethylcyclopentyl)benzene-1,4-diol 21: IR
(neat): mmax/cmꢀ1 3386; 1H NMR (300 MHz, CDCl3): d
6.74 (1H, s), 6.46 (1H, s), 4.49 (1H, s), 4.41 (1H, s), 2.60–
2.45 (1H, m), 2.15 (3H, s), 1.80–1.50 (5H, m), 1.38 (3H, s),
1.16 (3H, s), 0.76 (3H, s); 13C NMR (75 MHz, CDCl3): d
148.2 (C), 146.8 (C), 132 (C), 121.9 (C), 119.1 (CH), 116.2
(CH), 50.8 (C), 44.7 (C), 41.1 (CH2), 39.4 (CH2), 26.9
(CH3), 25.4 (CH3), 22.9 (CH3), 20.2 (CH2), 15.1 (CH3);
Mass: m/z 234 (M+, 30%), 164 (58), 151 (100), 137 (14).
4-Acetoxy-5-methyl-2-(1,2,2-trimethylcyclopentyl)phenyl
acetate 24: IR (neat): mmax/cmꢀ1 1762; 1H NMR (300
MHz, CDCl3): d 7.06 (1H, s), 6.82 (1H, s), 2.54–2.40
(1H, m), 2.30 (3H, s), 2.29 (3H, s), 2.12 (3H, s), 1.80–
1.45 (5H, m), 1.28 (3H, s), 1.12 (3H, s), 0.74 (3H, s); 13C
NMR (75 MHz, CDCl3): d 169.7 (C), 169.1 (C), 146.5 (C),
146.1 (C), 137.2 (C), 128.4 (C), 126.0 (CH), 122.9 (CH),
50.8 (C), 45.2 (C), 40.1 (CH2), 38.5 (CH2), 26.3 (CH3), 24.8
(CH3), 23.2 (CH3), 21.8 (CH3), 20.8 (CH3), 19.9 (CH2),
15.6 (CH3); Mass: m/z 318 (M+, 10%), 276 (24), 234 (100),
220 (14), 206 (9), 178 (13), 164 (61), 151 (45); HRMS: m/z
calcd for C19H26O4Na (M+Na): 341.1729. Found:
341.1729. 4-Acetoxy-5-methyl-2-(1,2,2-trimethylcyclopent-
yl)phenol 23 (revised HM-2): IR (neat): mmax/cmꢀ1 3461,
1731; 1H NMR (300 MHz, CDCl3): d 6.89 (1H, s), 6.52
(1H, s), 4.76 (1H, s), 2.60–2.40 (1H, m), 2.29 (3H, s), 2.07
(3H, s), 1.85–1.45 (5H, m), 1.39 (3H, s), 1.15 (3H, s), 0.76
(3H, s); 13C NMR (75 MHz, CDCl3): d 169.7 (C), 152.0
(C), 142.3 (C), 131.9 (C), 128.1 (C), 122.6 (CH),118.8
(CH), 50.8 (C), 44.8 (C), 41.0 (CH2), 39.3 (CH2), 26.8
(CH3), 25.4 (CH3), 22.7 (CH3), 20.8 (CH3), 20.2 (CH2),
15.5 (CH3); Mass: m/z 276 (M+, 23%), 234 (100), 177 (18),
References and notes
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3. To the best of our knowledge there is no report on the
syntheses of HM-1 to 4. Synthesis of HM-1 methyl ether
has been reported, but its conversion to HM-1 was not
described, hence, the structure of HM-1 was also not
confirmed until now. See: Paul, T.; Pal, A.; Gupta, P. D.;
Mukherjee, D. Tetrahedron Lett. 2003, 44, 737–740;
Srikrishna, A.; Rao, M. S. Synlett 2004, 374–376.
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som, T. J.; Li, T. T.; Faulkner, D. J.; Petersen, M. R.
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7. Even though signals due to methyl groups in the mono-
acetate 19 are in close agreement with those of HM-2,
considerable difference is present for the signals due to
aromatic protons, for example, for the two aromatic
protons Dd reported for HM-2 is 0.36; Dd found in 19 is
0.69.
8. Fuganti, C.; Serra, S. J. Chem. Soc., Perkin Trans. 1 2000,
3758–3764.
9. Toyota, M.; Koyama, H.; Asakawa, Y. Phytochemistry
1997, 46, 145–150.
10. The cuparene-1,4-diol 21 was found to be very sensitive
and readily undergoes oxidation to cuparene-1,4-qui-
none.9,11 As a result, a significant amount (ꢁ30%) of
cuparene-1,4-quinone formation was observed in the
acetylation and methylation reactions of cuparene-1,4-
diol 21.
11. Asakawa, Y.; Kondo, K.; Tori, M. Phytochemistry 1991,
30, 325–328.
12. Revision of the structure of HM-2 as a cuparene deriv-
ative, raises doubts about the structure of HM-3 as
herbertene. It may also be a cuparene, such as the
monoacetate of HM-4.
13. Yields refer to isolated and chromatographically pure
compounds. All the compounds exhibited spectral data
(IR, 1H and 13C NMR and mass) consistent with their
structures. Selected spectral data for ethyl cis-1,2-
dimethyl-2-(2,4-dimethoxy-5-methylphenyl)cyclopent-3-
enecarboxylate 12a: IR (neat): mmax/cmꢀ1 1722, 1611,
1
1586; H NMR (300 MHz, CDCl3+CCl4): d 6.88 (1H, s),
6.31 (1H, s), 5.77 (1H, dt, J 5.7 and 2.4 Hz), 5.71 (1H, dt,
J 5.7 and 2.1 Hz), 3.77 (6H, s), 3.42 and 3.33 (2H, q of AB
q, J 11.7 and 6.9 Hz), 2.99 (1H, dt, J 16.5 and 2.4 Hz), 2.24