Total Synthesis of Sphingofungin F

Abstract

A stereoselective approach toward sphingofungin F has been realized from l-quebrachitol. This synthesis featured a ­substrate-controlled asymmetric Michael addition, a regiospecific methylsulfonate elimination to construct the contiguous chiral ­centers in the target molecule.

sphingofungin F - total synthesis - Michael addition - l-quebrachitol - Wittig-type reaction

References and Notes

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Analytical Data of Compound 9.
Amorphous solid, [α]_D ²⁵ +15.6 (c 0.35, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.67-7.85 (m, 4 H), 7.29 (d, J = 8.2 Hz, 2 H), 6.95 (d, J = 8.4 Hz, 2 H), 4.65 (d, J = 11.0 Hz, 2 H), 4.43 (d, J = 4.1 Hz, 1 H), 4.40 (s, 3 H), 4.28 (m, 1 H), 4.19 (d, J = 10.6 Hz, 1 H), 4.07 (dd, J ₁ = 10.2 Hz, J ₂ = 9.0 Hz, 1 H), 3.92 (s, 3 H), 3.65 (dd, J ₁ = 9.6 Hz, J ₂ = 8.8 Hz, 1 H), 2.27 (d, J = 7.4 Hz, 2 H), 1.53 (s, 3 H), 1.49 (s, 3 H), 1.39 (s, 3 H), 1.34 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 171.03, 166.48, 166.50, 159.31, 158.70, 134.57, 134.45, 134.43, 133.63, 131.66, 131.38, 129.89, 129.50, 129.48, 116.45, 110.76, 110.54, 80.02, 79.89, 79.07, 76.75, 75.34, 73.36, 72.16, 71.40, 57.86, 27.33, 27.06, 26.68, 24.65. HRMS: m/z calcd for C₃₁H₃₅NO₁₀: 581.2261; found: 581.2263.

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Analytical Data of Compound 12.
Amorphous solid, [α]_D ²⁵ +20.3 (c 0.15, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.70-7.88 (m, 4 H), 7.27-7.33 (m, 6 H), 6.86-6.89 (m, 4 H), 6.85 (d, J = 8.3 Hz, 2 H), 4.63-4.68 (m, 6 H), 4.40 (d, J = 3.8 Hz, 1 H), 4.29 (m, 1 H), 3.90 (d, J = 10.6 Hz, 1 H), 3.83 (2 × s, 6 H), 3.80 (s, 3 H), 3.48 (dd, J ₁ = 10.6 Hz, J ₂ = 10.2 Hz, 1 H), 3.45 (dd, J ₁ = 10.6 Hz, J ₂ = 9.8 Hz, 1 H), 1.67 (s, 3 H), 1.36 (s, 3 H), 1.33 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.68, 166.50, 159.31, 159.16, 157.35, 138.56, 138.45, 135.46, 135.15, 134.43, 133.10, 131.58, 131.38, 130.73, 129.89, 129.50, 128.55, 128.38, 128.37, 128.00, 127.99, 113.91, 110.89, 83.22, 81.49, 81.28, 76.50, 75.60, 71.73, 69.19, 55.63, 27.35, 25.91.

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<A NAME="RS03406ST-24">24</A>

Analytical Data of Compound 6.
Amorphous solid, [α]_D ²⁵ +8.9 (c 0.20, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.74-7.90 (m, 4 H), 7.26-7.33 (m, 6 H), 6.86-6.89 (m, 4 H), 6.85 (d, J = 8.0 Hz, 2 H), 5.31 (s, 1 H), 4.64-4.68 (m, 4 H), 4.64 (d, J = 9.6 Hz, 2 H), 3.86 (d, J = 9.2 Hz, 1 H), 3.85 (s, 3 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.46 (dd, J ₁ = 9.6 Hz, J ₂ = 7.8 Hz, 1 H), 3.35 (br s, 1 H), 3.35 (s, 3 H), 1.66 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.78, 165.50, 159.31, 159.26, 139.77, 138.85, 138.46, 135.46, 135.02, 134.44, 133.20, 132.66, 131.75, 131.23, 129.89, 129.88, 128.05, 127.98, 127.85, 126.88, 110.91, 110.89, 83.63, 81.62, 81.28, 80.66, 75.81, 75.47, 74.27, 73.97, 55.23, 55.20. HRMS: m/z calcd for C₄₀H₄₁NO₉: 679.2781; found: 679.2785.

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<A NAME="RS03406ST-26">26</A>

Analytical Data for Compound 2 (Sphingofungin F).
Amorphous solid, [α]_D ²⁵ +1.33 (c 0.20, MeOH). ¹H NMR (400 MHz, CD₃OD): δ = 5.78 (dt, J ₁ = 15.6 Hz, J ₂ = 6.6 Hz, 1 H), 5.46 (dd, J ₁ = 15.5 Hz, J ₂ = 8.0 Hz, 1 H), 4.11 (t, J = 7.6 Hz, 1 H), 3.86 (br s, 1 H), 3.67 (d, J = 7.5 Hz, 1 H), 2.45 (t, J = 7.5 Hz, 4 H), 2.04-2.06 (m, 2 H), 1.49-1.56 (m, 4 H), 1.48 (s, 3 H), 1.26-1.43 (m, 12 H), 0.90 (t, J = 6.7 Hz, 3 H). ¹³C NMR (100 MHz, CD₃OD): δ = 214.53, 175.32, 135.75, 130.30, 76.25, 75.73, 72.44, 67.03, 43.50, 33.52, 32.79, 30.26, 30.03, 25.02, 23.67, 21.80, 14.43.