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DOI: 10.1055/s-0029-1218344
Total Synthesis of (+)-Cardiobutanolide through a Carbohydrate-Based Approach
Publication History
Publication Date:
03 November 2009 (online)
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Abstract
The naturally occurring styryllactone (+)-cardiobutanolide has been synthesized in a highly efficient manner using d-glucono-δ-lactone, as a chiral pool starting material. The synthesis involves the stereoselective addition of Grignard reagent to a chiral aldehyde, zinc-mediated reductive deoxygenation of 4-alkoxybut- 2-enoic acid moiety and asymmetric dihydroxylation as the key steps.
Key words
cardiobutanolide - δ-gluconolactone - chiron approach - reductive elimination process - asymmetric dihydroxylation
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References and Notes
Compound 5: [α]D
²5 +18.4
(c 1.0, CHCl3). ¹H
NMR (CDCl3, 300 MHz): δ = 1.08, 1.19,
1.22, 1.29 (5 × s, 21 H), 3.66-3.81 (m,
3 H), 3.86-3.93 (m, 2 H), 4.79 (d, J = 5.28 Hz,
1 H), 7.16-7.26 (m, 6 H), 7.28-7.43
(m, 7 H), 7.73 (d, J = 6.04 Hz,
2 H). ¹³C NMR (CDCl3,
75 MHz): δ = 19.6, 25.5 (3 C), 26.3 (2 C),
27.3 (2 C), 65.5, 76.3, 77.1, 77.7, 83.0, 109.3, 110.3,
127.5 (2 C), 127.6 (2 C), 128.0, 128.1 (2 C),
129.7 (2 C), 129.9 (2 C), 133.5, 133.9, 136.3
(2 C), 136.4 (2 C), 140.0. IR (KBr): 3436, 2998,
2872, 1375, 1160, 1071, 842, 703 cm-¹.
HRMS: m/z [M + Na]+ calcd
for C33H42O5: 415.2440; found:
415.2442.
Compound 7: ¹H
NMR (CDCl3, 300 MHz): δ = 1.07 (s,
9 H), 1.25 (s, 3 H), 1.29 (s, 3 H), 1.35-1.30
(m, 3 H), 3.02 (s, 1 H, OH), 3.67-3.71
(m, 1 H), 4.17-4.28 (m, 3 H), 4.79 (d, J = 5.28 Hz,
1 H), 7.14-7.28 (m, 8 H), 7.34-7.41
(m, 5 H), 7.69 (d, J = 6.78
Hz, 2 H). ¹³C NMR (CDCl3,
75 MHz): δ = 14.2, 19.35, 25.6 (3 C),
26.4 (2 C), 60.13, 62.13, 70.65, 74.25, 77.3, 79.75, 81.73,
108.75, 126.0, 128.1 (2 C), 128.6 (4 C), 129.3,
130.1 (4 C), 134.77 (2 C), 135.99 (2 C),
139.1 (2 C), 168.24. LCMS: m/z = 595 [M + Na]+.
Compound 8: ¹H NMR (CDCl3,
300 MHz): δ = 1.06 (s, 9 H), 1.24 (s,
3 H), 1.28 (s, 3 H), 1.32-1.37 (m, 3 H),
3.68-3.72 (m, 1 H), 3.83-3.87 (m, 1 H),
4.18-4.30 (m, 3 H), 4.79 (d, J = 6.23
Hz, 1 H), 5.77 (dd, J = 1.88,
15.67 Hz, 1 H), 6.59 (dd, J = 4.15,
15.67 Hz, 1 H), 7.16-7.29 (m, 8 H), 7.36-7.43 (m,
5 H), 7.69 (d, J = 7.55
Hz, 2 H). ¹³C NMR (CDCl3,
75 MHz): δ = 14.2, 19.5, 25.62 (3 C),
26.50 (2 C), 60.45, 69.4, 71.62, 75.94, 78.63, 111.7, 121.14,
126.0, 128.1 (2 C), 128.4 (4 C), 128.6 (2 C),
130.14 (4 C), 134.73 (2 C), 130.90 (2 C), 139.14,
149.45, 167.8. LCMS: m/z = 597 [M + Na]+.
Compound 9: ¹H NMR (CDCl3,
300 MHz): δ = 1.03 (s, 9 H), 1.06 (s,
3 H), 1.15 (s, 3 H), 1.29-1.32 (m, 3 H),
2.02 (s, 3 H), 3.66-3.70 (m, 1 H), 3.95-3.99
(m, 1 H), 4.09-4.21 (m, 3 H), 4.66 (d, J = 6.04 Hz,
1 H), 4.67 (dd, J = 5.85,
15.86 Hz, 1 H), 5.61 (dd, J = 1.32,
15.67 Hz, 1 H), 7.15-7.28 (m, 8 H), 7.30-7.38
(m, 5 H), 7.70 (d, J = 6.23
Hz, 2 H). ¹³C NMR (CDCl3,
75 MHz): δ = 13.98, 19.13, 20.52, 22.45 (2 C), 26.84
(3 C), 60.27, 70.81, 76.57, 77.74, 80.44, 109.89, 122.82,
127.18 (2 C), 128.0 (4 C), 129.50, 132.94 (4 C), 133.32
(2 C), 135.80 (2 C), 139.13, 139.35 (2 C),
142.04, 165.29, 169.14. LCMS: m/z = 639 [M + Na]+.
Compound
10: [α]D
²5 +88.75
(c 1.0, CHCl3). ¹H
NMR (CDCl3, 300 MHz): δ = 1.05 (s,
3 H), 1.06 (s, 3 H), 1.13 (s, 9 H), 1.25
(t, J = 7.17
Hz, 3 H), 2.55-2.63 (m, 2 H), 3.62-3.67
(m, 1 H), 3.80-3.85 (m, 1 H), 4.15 (q, J = 7.17 Hz, 2 H),
4.70 (d, J = 6.42
Hz, 1 H), 5.58-5.64 (m, 1 H), 6.66-6.67
(m, 1 H), 7.22-7.46 (m, 13 H), 7.64 (d, J = 6.42 Hz, 2 H). ¹³C
NMR (CDCl3, 75 MHz): δ = 14.22, 19.35,
25.51 (3 C), 26.90 (2 C), 34.53, 60.14, 75.68,
77.50, 81.45, 108.74, 126.19, 127.32 (2 C), 127.57, 127.84
(4 C), 129.88 (2 C), 130.12, 134.77 (4 C),
135.69 (2 C), 135.99 (2 C), 138.0, 168.0. IR (KBr):
3436, 2998, 2873, 1742, 1630, 1160, 1071, 843, 703 cm-¹.
HRMS: m/z [M + Na]+ calcd
for C34H42O5Si: 558.7824; found: 558.7835.
Compound 11: [α]D
²5 +92.72
(c 1.0, CHCl3). ¹H
NMR (CDCl3, 300 MHz): δ = 1.05 (s,
3 H), 1.06 (s, 3 H), 1.13 (s, 9 H), 1.25
(t, J = 7.17
Hz, 3 H), 2.53-2.62 (m, 2 H), 3.60-3.67
(m, 2 H), 3.80-3.85 (m, 2 H), 4.15 (q, J = 7.17 Hz, 2 H),
4.70 (d, J = 6.42
Hz, 1 H), 7.22-7.46 (m, 13 H), 7.64 (d, J = 6.42 Hz,
2 H). ¹³C NMR (CDCl3,
75 MHz): δ = 14.22, 19.35, 25.60 (3 C),
26.85 (2 C), 35.34, 60.18, 68.41, 75.60, 77.40, 77.5,
81.45, 108.80, 126.20, 127.52 (2 C), 127.84 (2 C),
129.88 (4 C), 134.77 (4 C), 135.69 (2 C),
135.99 (2 C), 138.0, 168.42. IR (KBr): 3650, 3446, 2992,
2872, 1742, 1071, 843, 703 cm-¹. HRMS: m/z [M + Na]+ calcd
for C34H44O7Si: 592.7932; found:
592.7943.
Compound 2: mp 192-193 ˚C
(Lit.³ 189-190 ˚C); [α]D
²5 +8.3
(c 0.4, MeOH). ¹H
NMR (CDCl3, 300 MHz): δ = 2.38 (d, J = 16.6 Hz
1 H), 2.85 (m, 1 H), 3.94 (d, J = 6.1
Hz, 1 H), 4.41 (d, J = 7.4
Hz, 1 H), 4.54 (dd, J = 3.1,
6.7 Hz, 1 H), 4.63 (br s, 1 H), 4.79 (d, J = 7.5 Hz,
1 H), 7.21-7.32 (m, 4 H), 7.43 (d, J = 6.7 Hz,
1 H). ¹³C NMR (CDCl3,
75 MHz): δ = 39.0, 70.5, 71.5, 75.4, 76.1, 88.4,
127.1, 128.0, 129.7, 144.1, 176.0. IR (KBr): 3514, 3475, 2931, 2854,
1761, 1317, 1445, 1206 cm-¹. HRMS: m/z [M + Na]+ calcd
for C13H16O6: 291.0846; found:
291.0843.