1-Adamantanecarboxylic acid esters of certain terpenols, sterols, and plant phenols

Article abstract of DOI:10.1023/A:1025474619550

Esters 1b-15b were prepared from cetyl alcohol 1a, terpenols 2a-6a, sterols 7a-10a, plant phenols 11a-13a, and alcohols 14a-15a by reaction with 1-adamantanecarboxylic acid chloride in the presence of pyridine.

Full text of DOI:10.1023/A:1025474619550

Chemistry of Natural Compounds, Vol. 39, No. 3, 2003
1-ADAMANTANECARBOXYLIC ACID ESTERS OF CERTAIN
TERPENOLS, STEROLS, AND PLANT PHENOLS
1
1
E. A. Dikusar, N. G. Kozlov,
UDC 547.82+547.92+547.362
1
2
V. I. Potkin, and N. V. Kovganko
Esters 1b-15b were prepared from cetyl alcohol 1a, terpenols 2a-6a, sterols 7a-10a, plant phenols 11a-13a,
and alcohols 14a-15a by reaction with 1-adamantanecarboxylic acid chloride in the presence of pyridine.
Key words: terpenols, sterols, phenols, alcohols, 1-adamantanecarboxylic acid, esters.
Adamantane derivatives exhibit a widespectrum ofbiological activity. Theyinclude compounds with antiviral, curare-
like, myorelaxant, anticholinesterase, psychostimulating, neurotropic, and local anesthetic activities [1]. Effective medicinal
preparationsbasedon adamantanesuch asmidantanum, memantine, gludantanum, remantadinum, andadaprominumhavebeen
produced [2]. New physiologically active compounds are created using the widely applied method of synthesizing analogs of
known active compounds, which are obtained by substituting one group in the starting compound by other fragments, in
particular, adamantane derivatives [3].
Onepromisingapproach tosynthesizingnewadamantane-containingbiologicallyactivecompoundsistheuseofesters,
which enables the construction of compounds that contain simultaneouslythe adamantane pharmacophore [1, 4] and structural
elements of terpenols, sterols, and plant alcohols and phenols [5-10].
Our goal was to prepare several new derivatives of natural compounds as esters of 1-adamantanecarboxylic acid. We
selected the following natural compounds for the synthesis: cetyl alcohol1a, terpenols[citronellol 2a, geraniol 3a, (-)-1R,2S,5R-
menthol 4a, borneol 5a, and isoborneol 6a], sterols (cholesterol 7a, β-sitosterol 8a, lanosterol 9a, and ergosterol 10a), plant
phenols (eugenol 11a, vanillin 12a, and vanillal 13a), and tetrahydrofurfuryl 14a and furfuryl 15a alcohols. The corresponding
esters of 1-adamantanecarboxylic acid 1b-15b were prepared by reacting 1-adamantanecarboxylic acid chloride with alcohols
and phenols 1a-15a in boiling absolute benzene in the presence of pyridine. The yields of the desired products were 77-91%.
Me(CH ) OR
2
15
OR
OR
1a-b
2a-b
3a-b
OR
5
3
1
OR
OR
4a-b
5a-b
6a-b
a: R = H;
b: R =
O
1
) Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072, Minsk, ul. Surganova,
3, e-mail: evgen 58@mail.ru; 2) Institute ofBioorganic Chemistry, National Academyof Sciences of Belarus, 220141, Minsk,
ul. Akad. Kuprevicha, 5/2, e-mail: kovganko@iboch.bas-net.by. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp.
1
2
15-218, May-June, 2003. Original article submitted May 13, 2003.
©
0
009-3130/03/3903-0276$25.00 2003 Plenum Publishing Corporation
2
76

RO
RO
RO
7a-b
8a-b
9a-b
CHO
OR
CHO
OR
MeO
EtO
OMe
OR
RO
1
0a-b
11a-b
12a-b
13a-b
OR
OR
O
O
a: R = H;
b: R =
1
4a-b
15a-b
O
The structures of 1b-15b were confirmed by elemental analyses, determination of molecular weights, and IR, UV, and
PMR spectra. The purity of the products was 98 ± 1%.
EXPERIMENTAL
IR spectra were recorded on a Protege-460 Fourier spectrophotometer in KBr disks (1b, 5b-13b) or as thin layers (2b-
4
b, 14b, 15b). PMR spectra were recorded on a Tesla 587A spectrometer (100 MHz) in CDCl solution. Chemical shifts are
3
given in the δ scale with TMS internal standard. UV spectra were recorded on a Specord UV-Vis instrument for solutions
-3
(
1·10 M) in n-butanol. Molecular weights (M) were determined cryoscopically in benzene. Column chromatography used
neutral Al O L 40/250 µm (Brockman, activity level II).
2
3
1
-Adamantanecarboxylic acid chloride was prepared by reacting 1-adamantanecarboxylic acid with thionylchloride
in benzene by the literature method [4].
1
-Adamantanecarboxylic Acid Esters 1b-15b (General Method). A solution of the appropriate alcohol or phenol
(
1a-15a, 10 mmol) in absolute benzene (100 mL) was treated with 1-adamantanecarboxylic acid chloride (10 mmol) and one
portion of pyridine (10 mmol). The reaction mixture was refluxed for 10-12 h and cooled to room temperature. The resulting
precipitate (pyridinium chloride) was filtered off. The filtrate was washed successively with water and sodium bicarbonate
solution (5%) and dried over CaCl . The desiccant was filtered off. The solvent was removed. Compounds 1b and 5b-13b were
2
purified by low-temperature crystallization from ethanol; 2b-4b, 14b, and 15b, by column chromatography over Al O with
2
3
elution by hexane.
This method was used to prepare:
-Hexadecanyl 1-Adamantylmethanoate (1b). Yield 93%, mp 25-26°C. Found (%): C 80.43, H 12.09. Cald. for
1
-1
C H O (%): C 80.14, H 11.96. M: found 381.5, cald. 404.7. IR spectrum (ν, cm ): 2925, 2855 (CHAlk); 1730 (C=O); 1470,
2
7
48
2
1
4
455 (CH ); 1270, 1235 (C–O). UV spectrum (λmax, ε): 207 (150), 218 (200). PMR spectrum (δ, ppm, J/Hz): 0.89 (t, CH3),
2
3
.03 (t, J = 6.2, CH O).
2
2
0
20
Citronellyl 1-Adamantylmethanoate (2b). Yield 90%, d20 1.0216, nD 1.4960. Found (%): C 79.34, H 10.93.
-1
Cald. for C H O (%): C 79.19, H 10.76. M: found 306.4, cald. 318.5. IR spectrum (ν, cm ): 3030 (=CH); 2955, 2907, 2852
21
34
2
(
(
CHAlk); 1727 (C=O); 1618 (C=C); 1453 (CH ); 1233, 1078 (C–O). UV spectrum (λmax, ε): 204 (4000). PMR spectrum
2
3
3
δ, ppm, J/Hz): 0.94 (d, J = 5.6, CH on C-3), 1.60 and 1.70 (2s, 2CH on C-7), 4.09 (t, J = 6.4, 2H-1), 4.95-5.25 (m, H-6).
3
3
277

2
0
20
Geraniyl 1-Adamantylmethanoate (3b). Yield 80%, d20 1.0158, nD 1.5025. Found (%): C 80.06, H10.24. Cald.
-1
for C H O (%): C 79.70, H 10.19. M: found 307.9, cald. 316.5. IR spectrum (ν, cm ): 3050, 3020 (=CH); 2960, 2907, 2852
21 32 2
(
(
CHAlk); 1727 (C=O); 1676, 1625 (C=C); 1453 (CH ); 1230, 1074 (C–O). UV spectrum (λmax, ε): 206 (8000). PMR spectrum
2
3
δ, ppm, J/Hz): 1.60 (s, CH on C-3), 1.70 (s, 2CH on C-7), 4.55 (d, J = 6.7, 2H-1), 4.95-5.45 (m, H-2, H-6).
3
3
2
0
20
(
-)-1R,2S,5R-Menthyl 1-Adamantylmethanoate (4b). Yield 78%, d20 1.0237, nD 1.4990. Found (%): C 79.50,
-1
H 10.93. Cald. for C H O (%): C 79.19, H 10.76. M: found 306.7, cald. 318.5. IR spectrum (ν, cm ): 2955, 2930, 2907,
2
1 34 2
2
852 (CHAlk); 1726 (C=O); 1453, 1433 (CH ); 1236, 1079 (C–O). UV spectrum (λmax, ε): 206 (150), 218 (200). PMR spectrum
2
3
3
(
δ, ppm, J/Hz): 0.74 (d, J = 6.7, CH on C-5), 0.94 (d, J = 6.7, 2CH on C-8), 4.50-4.80 (m, H-1).
3 3
Borneyl 1-Adamantylmethanoate (5b). Yield 82%, mp 176-177°C. Found (%): C 80.03, H 10.25. Cald. for
-1
C H O (%): C 79.70, H 10.19. M: found 303.2, cald. 316.5. IR spectrum (ν, cm ): 2980, 2955, 2935, 2905, 2850 (CHAlk);
2
1
32
2
1
725 (C=O); 1475, 1453 (CH ); 1240, 1076 (C–O). UV spectrum (λmax, ε): 206 (150), 218 (200). PMR spectrum (δ, ppm):
2
0
.80 (s, CH ), 0.86 (s, CH ), 0.89 (s, CH ), 4.75-4.93 (m, H-2).
3
3
3
Isoborneyl 1-Adamantylmethanoate (6b). Yield 84%, mp 145-146°C. Found (%): C 80.01, H 10.32. Cald. for
-1
C H O (%): C 79.70, H 10.19. M: found 308.6, cald. 316.5. IR spectrum (ν, cm ): 3005, 2985, 2955, 2932, 2905, 2850
2
1
32
2
(
CHAlk); 1722 (C=O); 1475, 1453 (CH ); 1238, 1075 (C–O). UV spectrum (λmax, ε): 206 (150), 218 (200). PMR spectrum
2
(
δ, ppm): 0.82 (s, 2CH ), 0.97 (s, CH ), 4.55-4.70 (m, H-2).
3
3
Cholesteryl 1-Adamantylmethanoate (7b). Yield 80%, mp 233-234°C. Found (%): C 83.28, H 11.16. Cald. for
-1
C H O (%): C 83.15, H 11.02. M: found 527.1, cald. 548.9. IR spectrum (ν, cm ): 3035 (=CH); 2935, 2906, 2860, 2850
3
8
60
2
(
CHAlk); 1680 (C=C); 1724 (C=O); 1466, 1452, 1445 (CH ); 1235, 1078 (C–O). UV spectrum (λmax, ε): 204 (4000). PMR
2
spectrum (δ, ppm): 0.69 (s, CH -18), 0.80-1.02 (m, CH -21, CH -26, CH -27), 1.03 (s, CH -19), 5.25-5.45 (m, H-6).
3
3
3
3
3
β-Sitosteryl 1-Adamantylmethanoate (8b). Yield 90%, mp 205-206°C. Found (%): C 83.44, H 11.31. Cald. for
-1
C H O (%): C 83.27, H 11.18. M: found 558.3, cald. 576.9. IR spectrum (ν, cm ): 3030 (=CH); 2955, 2933, 2907, 2860,
4
0
64
2
2
851 (CHAlk); 1726 (C=O); 1681 (C=C); 1465, 1452 (CH ); 1237, 1078 (C–O). UV spectrum (λmax, ε): 204 (5000). PMR
2
spectrum (δ, ppm): 0.69 (s, CH -18), 1.03 (s, CH -19), 4.35-4.85 (m, H-3); 5.27-5.50 (m, H-6).
3
3
Lanosteryl 1-Adamantylmethanoate (9b). Yield 86%, mp 196-197°C. Found (%): C 83.76, H 11.04. Cald. for
-1
C H O (%): C 83.61, H 10.95. M: found 571.4, cald. 589.0. IR spectrum (ν, cm ): 3030 (=CH); 2980, 2955, 2940, 2911,
4
1
64
2
2
852 (CHAlk); 1714 (C=O); 1679 (C=C); 1465, 1453 (CH ); 1249, 1082 (C–O). UV spectrum (λmax, ε): 203 (9000), 211 (7000).
2
PMR spectrum (δ, ppm): 0.70 (s, CH ), 0.85-0.95 (m, 4CH ), 1.02 (s, CH ), 1.55 and 1.63 (s, CH -26, CH -27), 4.30-4.60 (m,
3
3
3
3
3
H-3), 4.95-5.25 (m, H-24).
Ergosteryl 1-Adamantylmethanoate (10b). Yield 91%, mp 191-192°C. Found (%): C 84.04, H 10.51. Cald. for
-1
C H O (%): C 83.81, H 10.46. M: found 538.7, cald. 558.9. IR spectrum (ν, cm ): 3040 (=CH), 2953, 2934, 2906, 2868,
3
9
58
2
2
852 (CHAlk); 1726 (C=O); 1682, 1651 (C=C); 1454 (CH ); 1239, 1077 (C–O). UV spectrum (λmax, ε): 205 (17000), 260
2
(
7000), 270 (9000), 282 (9000), 294 (6000). PMR spectrum (δ, ppm): 0.64 (s, CH ), 0.80-1.05 (m, 4CH ), 1.09 (s, CH ), 4.40-
3 3 3
4
.90 (m, H-3), 5.10-5.75 (m, H-6, H-7, H-22, H-23).
Eugenyl 1-Adamantylmethanoate (11b). Yield 79%, mp 86-87°C. Found (%): C 77.52, H 8.18. Cald. for C H O
3
21
26
-1
(%): C 77.27, H 8.03. M: found 318.3, cald. 326.4. IR spectrum (ν, cm ): 3070 (=CH); 3055, 3000 (CH ); 2970, 2955, 2932,
Ar
2
905, 2852 (CHAlk); 1742 (C=O); 1640 (C=C); 1605, 1509, 1460, 1450, 1422 (Ar); 1286, 1261, 1219, 1197, 1186, 1149, 1054,
1
036 (C–O); 909, 842 (CH ). UV spectrum (λmax, ε): 207 (14000), 218 (8000), 272 (3000), 281 (3000). PMR spectrum (δ,
Ar
3
ppm, J/Hz): 3.35 (d, J = 6.7, CH ), 3.79 (s, CH O), 4.90-5.25 (m, =CH ), 5.70-6.25 (m, =CH), 6.60-7.00 (m, 3H ).
2
3
2
Ar
Vanillinyl 1-Adamantylmethanoate (12b). Yield 79%, mp 118-119°C. Found (%): C 72.71, H 7.11. Cald. for
-1
C H O (%): C 72.59, H 7.05. M: found 303.1, cald. 314.4. IR spectrum (ν, cm ): 3080, 3005 (CH ); 2970, 2934, 2905,
1
9
22
4
Ar
2
895, 2855, 2825 (CHAlk); 1743, 1696 (C=O); 1601, 1593, 1508, 1469, 1454, 1425, 1379 (Ar); 1325, 1289, 1262, 1215, 1200,
1
175, 1155, 1109, 1045 (C–O); 865, 850, 784, 760, 730, 675 (CH ). UV spectrum (λmax, ε): 205 (9000), 223 (14000), 260
Ar
(
8000), 308 (3000). PMR spectrum (δ, ppm): 3.89 (s, CH O), 7.10-7.55 (m, 3H ), 9.94 (s, CHO).
3
Ar
Vanillalyl 1-Adamantylmethanoate (13b). Yield 81%, mp 106-107°C. Found (%): C 73.29, H 7.43. Cald. for
-1
C H O (%): C 73.15, H 7.37. M: found 321.5, cald. 328.4. IR spectrum (ν, cm ): 3070, 3050, 2995 (CH ); 2980, 2909,
1
0
24
4
Ar
2
1
852, 2825 (CHAlk); 1752, 1702 (C=O); 1601, 1585, 1506, 1475, 1455, 1430, 1395, 1380 (Ar); 1325, 1290, 1263, 1210, 1198,
180, 1157, 1115, 1100, 1038 (C–O); 860, 850, 790, 780, 760, 740, 675 (CH ). UV spectrum (λmax, ε): 205 (9000), 224
Ar
3
3
(13000), 260 (8000), 309 (3000). PMR spectrum (δ, ppm, J/Hz): 1.41 (t, J = 7.3, CH ), 4.12 (q, J = 7.3, CH ), 7.10-7.55 (m,
3 2
3
H ), 9.93 (s, CHO).
Ar
2
78

2
0
20
Tetrahydrofurfuryl 1-Adamantylmethanoate (14b). Yield 79%, d20 1.0171, nD 1.5085. Found (%): C 73.02,
-1
H 9.26. Cald. for C H O (%): C 72.69, H 9.15. M: found 248.8, cald. 264.4. IR spectrum (ν, cm ): 2955, 2940, 2906, 2852
1
6 24 3
(
CHAlk); 1728 (C=O); 1453 (CH ); 1268, 1234, 1184, 1104, 1074, 1021 (C–O). UV spectrum (λmax, ε): 215 (100). PMR
2
spectrum (δ, ppm): 1.50-2.25 [19H, m, (CH ) and C H ], 3.60-4.40 (m, –CHO– and 2CH O).
2
2
10 15
2
2
0
20
Furfuryl 1-Adamantylmethanoate (15b). Yield 77%, d20 1.0510, nD 1.5240. Found (%): C 74.09, H 7.93. Cald.
for C H O (%): C 73.82, H 7.74. M: found 251.1, cald. 260.3. IR spectrum (ν, cm ): 3150, 3120 (CH ); 2940, 2907, 2852
-1
16
20
3
Ar
(CHAlk); 1727 (C=O); 1678, 1656 (C=C); 1503, 1453 (Ar); 1323, 1268, 1230, 1184, 1152, 1103, 1069, 1016, 980, 955, 921
(
C–O); 815, 741, 675, 600 (CH ). UV spectrum (λmax, ε): 218 (7000). PMR spectrum (δ, ppm): 1.55-2.15 (15H, m, C H ),
Ar
10 15
5
.02 (2H, s, CH O), 6.25-6.40 [m, 2(–CH=)], 7.35-7.45 (m, =CHO–).
2
ACKNOWLEDGMENT
We thank the Belorussian Republic Foundation for Basic Research (Grant X 03-079), INTAS (Grant 99-00806), and
INTERBIOSCREEN (Moscow) for supporting the work.
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