PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.31 (6H, s, 2 × CH -8), 1.82 (2H, t, J = 6.4, CH -7), 2.31 (3H,
6
3
2
s, CH -4), 2.81 (2H, t, J = 6.4, CH -6), 3.62 (2H, s, CH -3), 3.65 (3H, s, COOCH ), 6.65 (1H, s, H-10), 7.56 (1H, s, H-5).
3
2
2
3
(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)aceticAcid (4). A solution of 3 (22.15 g, 70 mmol)
in propanol-2 (50 mL) was treated with NaOH solution (150 mL, 150 mmol, 1 M), and heated and stirred vigorously for 1 h
(course of reaction monitored using TLC). When the reaction was finished the mixture was cooled, poured into water
(500 mL), and acidified to pH 5-6. The resulting precipitate was filtered off and crystallized from aqueous propanol-2. Yield
18.62 g (88%), mp 181-182°C, C H O .
17 18
5
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.30 (6H, s, 2 × CH -8), 1.81 (2H, t, J = 6.4, CH -7), 2.32 (3H,
6
3
2
s, CH -4), 2.81 (2H, t, J = 6.4, CH -6), 3.54 (2H, s, CH -3), 3.65 (3H, s, COCH ), 6.67 (1H, s, H-10), 7.54 (1H, s, H-5), 12.10
3
2
2
3
(1H, br.s, COOH).
General Method for Synthesizing N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-
yl)acetyl]amino Acids 5-17. A solution of 4 (0.91 g, 3 mmol) and N-hydroxysuccinimide (0.38 g, 3.3 mmol) in anhydrous
dioxane (20 mL) was stirred vigorously, treated with diisopropylcarbodiimide (0.52 mL, 3.3 mmol), and stirred for 2 h (course
of reaction monitored by TLC). The resulting activated ester was treated with the appropriate amino acid (3.3 mmol) and
NaHCO (0.28 g, 3.3 mmol) in water (20 mL) and stirred vigorously for 2-4 h (course of reaction monitored by TLC). When
3
the reaction was finished the precipitate of diisopropylurea was filtered off. The filtrate was diluted with water (200 mL) and
acidified to pH 5-6. The resulting precipitate was filtered off and crystallized from aqueous propanol-2.
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]glycine (5). Yield 0.73 g (68%),
mp 216-217°C, C H NO .
19 21
6
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.30 (6H, s, 2 × CH -8′), 1.81 (2H, t, J = 6.4, CH -7′), 2.31 (3H,
6
3
2
s, CH -4′), 2.81 (2H, t, J = 6.4, CH -6′), 3.50 (2H, s, CH -3′), 3.72 (2H, d, J = 6.0, CH -2), 6.67 (1H, s, H-10′), 7.54 (1H, s,
3
2
2
2
H-5′), 8.19 (1H, t, J = 5.6, CONH), 12.50 (1H, br.s, COOH).
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]-β-alanine (6). Yield 0.82 g (73%),
mp 184-185°C, C H NO .
20 23
6
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.33 (6H, s, 2 × CH -8′), 1.83 (2H, t, J = 6.4, CH -7′), 2.31 (3H,
6
3
2
s, CH -4′), 2.38 (2H, t, J = 6.8, CH -2), 2.84 (2H, t, J = 6.4, CH -6′), 3.25 (2H, q, J = 6.8, CH -3), 3.44 (2H, s, CH -3′), 6.69
3
2
2
2
2
(1H, s, H-10′), 7.56 (1H, s, H-5′), 7.97 (1H, t, J = 5.6, CONH), 12.30 (1H, br.s, COOH).
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]-4-aminobutanoicAcid (7). Yield 0.91
g (78%), mp 172-173°C, C H NO .
21 25
6
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.33 (6H, s, 2 × CH -8′), 1.65 (2H, m, CH -3), 1.83 (2H, t,
6
3
2
J = 6.6, CH -7′), 2.19 (2H, t, J = 7.2, CH -2), 2.32 (3H, s, CH -4′), 2.84 (2H, t, J = 6.6, CH -6′), 3.04 (2H, q, J = 6.6, CH -4),
2
2
3
2
2
3.40 (2H, s, CH -3′), 6.60 (1H, s, H-10′), 7.48 (1H, s, H-5′), 7.85 (1H, t, J = 5.4, CONH), 11.92 (1H, br.s, COOH).
2
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]-6-aminohexanoic Acid (8). Yield
0.80 g (64%), mp 168-169°C, C H NO .
23 29
6
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.25 (2H, m, CH -4), 1.33 (6H, s, 2 × CH -8′), 1.37 (2H, m,
6
2
3
CH -3), 1.48 (2H, m, CH -5), 1.83 (2H, t, J = 6.6, CH -7′), 2.32 (3H, s, CH -4′), 2.84 (2H, t, J = 6.6, CH -6′), 3.02 (2H, q,
2
2
2
3
2
J = 6.8, CH -6), 3.43 (2H, s, CH -3′), 6.69 (1H, s, H-10′), 7.55 (1H, s, H-5′), 7.84 (1H, t, J = 5.6, CONH), 11.98 (1H, br.s,
2
2
COOH).
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]-L-alanine (9). Yield 0.96 g (86%),
mp 221-222°C, C H NO .
20 23
6
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.31 (3H, d, J = 7.2, CH -2), 1.33 (6H, s, 2 × CH -8′), 1.83 (2H,
6
3
3
t, J = 6.9, CH -7′), 2.30 (3H, s, CH -4′), 2.83 (2H, t, J = 6.9, CH -6′), 3.48 (2H, s, CH -3′), 4.20 (1H, m, H-2), 6.59 (1H, s,
2
3
2
2
H-10′), 7.47 (1H, s, H-5′), 8.12 (1H, d, J = 7.2, CONH), 12.10 (1H, br.s, COOH).
N-[(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetyl]-DL-2-aminobutanoicAcid (10). Yield
0.92 g (79%), mp 216-217°C, C H NO .
21 25
6
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.91 (3H, t, J = 7.5, CH -4), 1.33 (6H, s, 2 × CH -8′), 1.60-1.80
6
3
3
(2H, m, CH ), 1.83 (2H, t, J = 6.9, CH -7′), 2.31 (3H, s, CH -4′), 2.83 (2H, t, J = 6.9, CH -6′), 3.51 (2H, s, CH -3′), 4.12 (1H,
2
2
3
2
2
m, H-2), 6.59 (1H, s, H-10′), 7.46 (1H, s, H-5′), 8.05 (1H, d, J = 7.2, CONH), 11.95 (1H, br.s, COOH).
171