Syntheses of the Macrolide Subunits of Merremoside-type Resin Glycosides

Xing-Mei Zhu; Li-Li He; Guang-Li Yang; Ming Lei; Si-Shi Chen; Jin-Song Yang

doi:10.1055/s-2006-956493

LETTER

Syntheses of the Macrolide Subunits of Merremoside-type Resin Glycosides

Xing-Mei Zhu, Li-Li He, Guang-Li Yang, Ming Lei, Si-Shi Chen, Jin-Song Yang**
Department of Chemistry of Medicinal Natural Products and Key Laboratory of Drug Targeting, School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
Fax: +86(28)85503723; e-Mail: yjs@scu.edu.cn;

Abstract

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Abstract

The 20- and 21-membered macrolide subunits of merremoside-type resin glycosides with interesting bioactivity were synthesized via a macrolactonization approach using Corey-Nicolaou protocol in 14 steps with overall yields of 0.7% for 17 and 3.5% for 18 from (R)-glycidol. Further debenzylation of the macrolide 18 led to diol 19 that might act as the key substrate for transformation into merremosides A-G.

Key words

resin glycoside - merremoside - macrolide - synthesis - macrolactonization

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References

References and Notes

Current address: Department of Chemistry, Fourth Military Medical University, Xi’an 710032, P. R. of China.

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Typical Procedure for Macrolactonization: Under argon, a solution of glycosidic acid 16 (150 mg, 0.22 mmol), (PyS)₂ (225 mg, 1.0 mmol), and Ph₃P (303 mg, 1.2 mmol) in anhyd toluene (6 mL) was stirred for 6 h at r.t. The mixture was diluted with deoxygenated anhyd toluene (20 mL) and then was added dropwise by a syringe pump to refluxing anhyd toluene (280 mL) for 12 h. The solution was refluxed under argon for 7 d until the complete disappearance of 16 (judged by TLC analysis). The reaction mixture was concentrated under reduced pressure. The residue was subjected to silica gel column chromatograph (PE-EtOAc, 6:1) to afford the macrolides 17 (20 mg, 11%) as a colorless syrup together with 18 (75 mg, 58%) as a colorless syrup. Spectral data for 17: R _f 0.11 (PE-EtOAc, 6:1); [α]_D ²¹ -8.09 (c = 0.68, CHCl₃). IR (KBr): 3436, 3063, 2906, 1737, 1602, 1496, 1081, 1052 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.86 (t, J = 6.8 Hz, 3 H), 1.16-1.34 (m, 28 H), 1.45-1.68 (m, 2 H), 1.34, 1.50 (s, 6 H, 2 × CH₃), 2.34 (t, J = 6.4 Hz, 2 H), 3.37-3.46 (m, 1 H), 3.55-3.60 (m, 2 H), 3.91-4.02 (m, 2 H), 4.05-4.07 (m, 2 H), 4.22 (t, J = 4.8 Hz, 1 H), 4.60 (d, J = 10.8 Hz, 1 H), 4.68 (d, J = 10.8 Hz, 1 H), 4.91 (s, 1 H), 5.13 (s, 1 H), 5.35 (dd, J = 2.4, 9.6 Hz, 1 H), 7.26-7.35 (m, 5 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.1, 17.8, 19.7, 22.6, 22.7, 23.8, 24.5, 24.8, 25.9, 26.1, 27.1, 27.7, 29.3, 30.0, 31.9, 32.7, 33.9, 37.1, 66.2, 69.2, 71.0, 73.9, 74.1, 74.7, 76.6, 78.5, 78.9, 80.3, 96.7, 98.0, 109.7, 127.7, 127.8, 128.3, 173.2. HR-ESI-MS: m/z [M + Na]⁺ calcd for C₃₈H₆₀O₁₀: 699.4084; found: 699.4079. 18: R _f 0.12 (PE-EtOAc, 6:1); [α]_D ²¹ -24.55 (c = 0.5, CHCl₃). IR (KBr): 3438, 3066, 2926, 1735, 1602, 1494, 1080, 1051 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.23 (d, J = 6.0 Hz, 3 H), 1.28 (d, J = 6.4 Hz, 3 H), 1.24-1.43 (m, 22 H), 1.61-1.73 (m, 2 H), 1.34, 1.52 (s, 6 H, 2 × CH₃), 2.32-2.39 (m, 1 H), 2.45-2.52 (m, 1 H), 3.36 (dd, J = 2.8, 8.4 Hz, 1 H), 3.46-3.51 (m, 1 H), 3.52 (dd, J = 7.2, 10.0 Hz, 1 H), 3.85-3.94 (m, 2 H), 4.02 (d, J = 5.2 Hz, 1 H), 4.15 (br s, 1 H), 4.19 (dd, J = 5.6, 6.8 Hz, 2 H), 4.53 (d, J = 11.2 Hz, 1 H), 4.73 (d, J = 11.6 Hz, 1 H), 5.01 (s, 1 H), 5.10 (dd, J = 2.8, 5.2 Hz, 1 H), 5.29 (d, J = 5.2 Hz, 1 H), 7.26-7.38 (m, 5 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.0, 17.7, 19.0, 22.6, 22.7, 23.0, 24.9, 25.7, 26.6, 27.7, 28.0, 28.1, 29.3, 29.7, 32.0, 32.8, 33.9, 34.9, 64.3, 67.9, 69.7, 72.4, 73.4, 75.9, 77.7, 77.9, 81.0, 83.5, 95.5, 96.5, 109.5, 127.9, 128.0, 128.5, 137.7, 173.2. HR-ESI-MS: m/z [M + Na]⁺ calcd for C₃₈H₆₀O₁₀: 699.4084; found: 699.4079.

Spectral data for 19: R _f 0.15 (PE-EtOAc, 2:1); [α]_D ²¹ -19.1 (c = 0.44, CHCl₃). IR (KBr): 3394, 2924, 1740, 1079, 1051 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, J = 6.6 Hz, 3 H), 1.26 (d, J = 7.8 Hz, 3 H), 1.35 (d, J = 7.2 Hz, 3 H), 1.24-1.52 (m, 24 H), 1.31, 1.50 (s, 6 H, 2 × CH₃), 2.34-2.43 (m, 2 H), 3.51 (dd, J = 8.1, 9.9 Hz, 2 H), 3.91-4.05 (m, 5 H), 4.47 (dd, J = 6.0, 6.6 Hz, 1 H), 4.97 (t, J = 7.8 Hz, 1 H), 5.00 (s, 1 H), 5.07 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.0, 17.7, 22.5, 22.7, 23.6, 25.0, 25.3, 27.6, 28.2, 28.6, 28.7, 29.3, 30.0, 31.7, 32.0, 33.1, 33.4, 34.5, 63.5, 66.7, 71.0, 73.1, 74.4, 75.3, 75.9, 79.7, 80.0, 93.5, 95.3, 109.4, 173.7. HR-ESI-MS: m/z [M + Na]⁺ calcd for C₃₁H₅₄O₁₀: 609.3615; found: 609.3609.