Stereoselective Total Synthesis of (-)-Isocladospolide B and Cladospolide B and C

Abstract

The enantioselective synthesis of bioactive butenolides isocladospolide B, cladospolide B, and cladospolide-C has been achieved from (S)-propylene oxide. Of the three stereogenic centers, the C-4/C-5 vic-diol was obtained using diastereo- and enantio­selective Brown hydroxycrotylation, while the C-11 stereocenter was created by Jacobsen hydrolytic kinetic resolution.

Key words

Brown hydroxycrotylation - Jacobsen hydrolytic kinetic resolution - butenolide macrolactones

References and Notes

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15

The ^¹H NMR and ^¹³C NMR spectroscopic data, specific rotation, and mp match the reported data for cladospolide B (2), cladospolide C (3), and isocladospolide B (5).
Spectroscopic Data for Representative Compounds 2 Colorless solid; mp 100-101 ˚C (lit.^¹b mp 98-102 ˚C); [α]_D ^²9 +24.2 (c 1.5, CHCl₃) {lit.^¹b [α]_D +26.9 (c 0.4, MeOH)}. ^¹H NMR (300 MHz, CDCl₃): δ = 1.27 (d, 3 H, J = 6.0 Hz, H-12), 1.34-2.08 (m, 10 H, 5 × CH₂), 2.45 (br s, 2-OH), 3.88 (dtd, 1 H, J = 1.5, 4.0, 8.6 Hz, H-5), 4.97 (qdd, 1 H, J = 0.3, 6.0, 9.2 Hz, H-11), 5.11 (ddd, 1 H, J = 1.2, 4.0, 8.6 Hz, H-4), 5.85 (dd, 1 H, J = 1.1, 12.0 Hz, H-2), 6.13 (dd, 1 H, J = 8.6, 12.0 Hz, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 17.3, 20.3, 20.5, 25.0, 29.6, 30.9, 67.9, 72.5, 73.1, 122.3, 145.2, 166.1. IR (neat): 3454, 3298, 2927, 2859, 1710, 1463, 1285, 1106, 1043, 823 cm^-¹. ESI-MS: m/z = 251 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₂H₂₀O₄Na [M + Na]⁺: 251.1259; found: 251.1267.
Compound 3
Colorless solid; mp 92-93 ˚C (lit.^¹b mp 90-91 ˚C); [α]_D ^³¹ +36.7 (c 0.3, CHCl₃) {lit.^¹a [α]_D +59.7 (c 0.4, MeOH)}. ^¹H NMR (300 MHz, CDCl₃): δ = 1.31 (d, 3 H, J = 6.0 Hz, H-12), 1.23-1.28 (m, 10 H, 5 × CH₂), 2.54 (br s, OH), 3.56 (t, 1 H, J = 7.7 Hz, H-5), 3.98 (dd, 1 H, J = 7.7, 9.1 Hz, H-4), 4.92-5.02 (m, 1 H, H-11), 6.05 (d, 1 H, J = 15.8 Hz, H-2), 6.81 (dd, 1 H, J = 9.4, 15.8 Hz, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.8, 24.5, 27.2, 29.7, 32.1, 33.9, 74.4, 76.6, 77.5, 124.5, 145.3, 166.1. IR (neat): 3321, 1725, 1637, 1352, 1219, 1109, 772 cm^-¹. ESI-MS: m/z = 251 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₂H₂₀O₄Na [M + Na]⁺: 251.1259; found: 251.1269.
Compound 5
Colorless syrup; [α]_D ^²9 -56.6 (c 1.0, CHCl₃) {lit.^²b [α]_D -61.0 (c 16.6, MeOH)}. ^¹H NMR (300 MHz, CDCl₃): δ = 1.17 (d, 3 H, J = 6.0 Hz, H-12), 1.20-1.63 (m, 10 H, 5 × CH₂), 1.82 (br s, 2-OH), 3.70-3.84 (m, 2 H, H-11, H-5), 4.98 (ddd, 1 H, J = 1.5, 2.3, 4.5 Hz, H-4), 6.18 (dd, 1 H, J = 2.3, 6.0 Hz, H-2), 7.46 (dd, 1 H, J = 1.5, 6.0 Hz, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 23.9, 25.8, 25.9, 29.7, 33.5, 39.5, 68.5, 72.1, 86.6, 123.1, 154.2, 173.4. IR (neat): 3452, 3370, 2930, 2854, 1748, 1465, 1172, 831 cm^-¹. ESI-MS: m/z = 251 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₂H₂₀O₄Na [M + Na]⁺: 251.1259; found: 251.1271.
Compound 12
[α]_D ^³0 +18.7 (c 1.0, CHCl₃). ^¹H NMR (300 MHz, CDCl₃):
δ = 0.02 (s, 6 H), 0.87 (s, 9 H), 1.09 (d, 3 H, J = 6.0 Hz), 1.23-1.59 (m, 8 H), 1.74-2.16 (m, 2 H), 2.27-2.55 (m, 1 H), 3.36 (d, 3 H, J = 3.6 Hz), 3.63 (br s, OH), 3.68-3.81 (m, 1 H), 3.83-4.07 (m, 1 H), 4.54 (dd, 1 H, J = 4.2, 6.6 Hz), 4.68 (d, 3 H, J = 6.6 Hz), 5.23-5.37 (m, 2 H), 5.57-5.86 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = -4.7, -4.5, 18.1, 23.8, 25.7, 25.9, 29.7, 32.1, 34.3, 39.6, 55.5, 68.6, 73.2, 80.8, 93.8, 120.0, 133.6. IR (neat): 3436, 2927, 2857, 1641, 1460, 1031, 769 cm^-¹. ESI-MS: m/z = 383 [M + Na]⁺. ESI-HRMS:
m/z calcd for C₁₉H₄₀O₄NaSi [M + Na]⁺: 383.2593; found: 383.2579.
Compound 15
[α]_D ^³¹ +23.6 (c 1.0, CHCl₃). ^¹H NMR (300 MHz, CDCl₃):
δ = 1.19 (d, 3 H, J = 6.0 Hz), 1.42 (s, 3 H), 1.43 (s, 3 H), 1.28-1.72 (m, 10 H), 3.69-3.78 (m, 1 H), 3.83 (q, 1 H, J = 6.0 Hz,), 5.27 (dt, 1 H, J = 1.0, 9.0 Hz), 5.64 (br s, 2-OH), 5.94 (dd, 1 H, J = 1.0, 11.3 Hz), 6.23 (dd, 1 H, J = 8.3, 11.3 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 23.1, 25.0, 25.1, 27.0, 27.3, 29.3, 31.6, 38.7, 68.2, 76.0, 80.8, 109.3, 122.4, 147.4, 169.1. IR (neat): 3473, 2934, 1722, 1661, 1371, 1174, 1036, 979 cm^-¹. ESI-MS: 309 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₅H₂₆O₄NaSi [M + Na]⁺: 309.1682; found: 309.1678.