Total Synthesis of Mniopetals A, B, C and D

Dedicated to Prof. Dr. W. Steglich on the occasion of his 80^th birthday

Abstract

A total synthesis of the mniopetals A, B, C and D is described. Key steps are a Sharpless asymmetric dihydroxylation and a selective esterification of an equatorial hydroxy group vicinal to an axial hydroxy function.

Key words

asymmetric synthesis - antiviral agents - chemoselectivity - intramolecular Diels–Alder reaction - natural products

• References and Notes

• 1a Kuschel A, Anke T, Velten R, Klostermeyer D, Steglich W, König B. J. Antibiot. 1994; 47: 733
• 1b Velten R, Klostermeyer D, Steffan B, Steglich W, Kuschel A, Anke T. J. Antibiot. 1994; 47: 1017
• 1c Velten R, Steglich W, Anke T. Tetrahedron: Asymmetry 1994; 5: 1229
• 1d Inchausti A, Yaluff G, De Arias AR, Ferreira ME, Nakayama H, Schinini A, Lorenzen K, Anke T, Fournet A. Phytother. Res. 1997; 11: 193
• 2a Suzuki Y, Ohara A, Sugaya K, Takao K.-I, Tadano K.-I. Tetrahedron 2001; 57: 7291
• 2b Jauch J. Eur. J. Org. Chem. 2001; 473
• 2c Reiser U, Jauch J. Synlett 2001; 90
• 2d Jauch J. Synlett 2001; 87
• 2e Suzuki Y, Nishimaki R, Ishikawa M, Murata T, Takao K.-I, Tadano K.-I. J. Org. Chem. 2000; 65: 8595
• 2f Suzuki Y, Nishimaki R, Ishikawa M, Murata T, Takao K.-I, Tadano K.-I. Tetrahedron Lett. 1999; 40: 7835
• 2g Jauch J. Synlett 1999; 1325
• 2h Murata T, Ishikawa M, Nishimaki R, Tadano K.-I. Synlett 1997; 1291
• 3a Murakami T, Hirono R, Furusawa K. Tetrahedron 2005; 61: 9233
• 3b Adam W, Lazarus M, Schmerder A, Humpf H.-U, Saha-Möller CR, Schreier P. Eur. J. Org. Chem. 1998; 2013
• 3c Döbler C, Beller M, Mehltretter G. Angew. Chem. Int. Ed. 1999; 38: 3026 ; Angew. Chem. 1999, 111, 3211
• 3d Aladro FJ, Guerra FM, Massanet GM. Tetrahedron Lett. 2000; 41: 3209
• 3e Morrill C, Grubbs RH. J. Am. Chem. Soc. 2005; 127: 2842
• 3f Huang K, Liu HW, Dou X, Huang M.-Y, Jiang Y.-Y. Polym. Adv. Technol. 2003; 14: 364
• 4 For a similar use of MOM acetals, see, e.g.: Fürstner A, Nagano T, Müller C, Seidel G, Müller O. Chem. Eur. J. 2007; 13: 1452
• 5 Mosher HS. J. Am. Chem. Soc. 1973; 95: 512
• 6 For the preparation of THP acetals, see, for example: Parry RJ, Burns MR, Skae PN, Pal B. Bioorg. Med. Chem. 1996; 4: 1077
• 7 Synthesis of Compound 15: 3,4-Dihydro-2H-pyran (565 μL, 6.18 mmol) was added to a mixture of 14 (324 mg, 1.24 mmol) and pyridinium p-toluenesulfonate (31.0 mg, 0.124 mmol) in CH₂Cl₂ (5.0 mL) and the reaction mixture was stirred at r.t. for 2 h. Sat. aq NaHCO₃ solution was added. Extraction with CH₂Cl₂, drying over MgSO₄ and purification by flash chromatography (petroleum ether–Et₂O, 2:1; silica gel, R_f 0.18 and 0.24) led to 15 (348 mg, 1.00 mmol, 81.0%). Specifications for one THP-diastereomer (R_f 0.24): ¹H NMR (500 MHz, CDCl₃): δ = 9.47 (s, 1 H, H-12), 7.17 (br d, J = 6.4 Hz, 1 H, H-7), 6.18 (dt, J = 10.2, 1.8 Hz, 1 H, H-1), 5.88 (dt, J = 10.2, 4.0 Hz, 1 H, H-2), 5.53 (s, 1 H, H-11), 5.07 (t, J = 2.8 Hz, 1 H, H-1′), 4.08 (dt, J = 11.1, 2.6 Hz, 1 H, H-5′_ax), 3.65 (br d, J = 11.5 Hz, 1 H, H-5′_eq), 3.20 (br s, 1 H, H-9), 2.55 (dm, J = 19.5 Hz, 1 H, H-6_ax), 2.43 (ddm, J = 19.5, 12.5 Hz, 1 H, H-6_eq), 2.00 (dd, J = 4.0, 2.1 Hz, 2 H, H-3), 1.82–1.93 (m, 1 H, H-3′_ax), 1.80–1.63 (m, 5 H, H-5, H-2′, H-4′), 1.57–1.63 (m, 1 H, H-3′_eq), 1.24 (s, 3 H, H-14), 1.04 (s, 3 H, H-13). ¹³C NMR (125 MHz, CDCl₃): δ = 192.7 (C-12), 175.3 (C-15), 156.0 (C-7), 138.9 (C-8), 129.5 (C-2), 126.2 (C-1), 99.2 (C-11), 94.7 (C-1′), 61.4 (C-5′), 49.9 (C-9), 48.2 (C-10), 44.9 (C-5), 41.2 (C-3), 31.14 (C-13), 31.05 (C-4), 29.8 (C-2′), 25.2 (C-4′), 24.6 (C-6), 24.2 (C-14), 18.1 (C-3′). [α]²⁰ _D –22.2 (CHCl₃, c = 0.1). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₀H₂₆O₅Na: 369.1678; found: 369.1634.
• 8a Altenbach H.-J, Voss B, Vogel E. Angew. Chem. Int. Ed. 1983; 22: 410 ; Angew. Chem. 1983, 95, 424
• 8b Van Rheenen V, Kelly RC, Cha DY. Tetrahedron Lett. 1976; 1973
• 9 Fattorusso E, Romano A, Bavestrello G, Bonelli P, Calcinai B. Tetrahedron Lett. 2006; 47: 2197
• 10a Bhat SV, Bajwa BS, Dornauer H, de Souza NJ. J. Chem. Soc., Perkin Trans. 1 1982; 767
• 10b Steglich W, Höfle G. Angew. Chem. Int. Ed. 1969; 8: 981 ; Angew. Chem. 1969, 81, 1001
• 10c Neises B, Steglich W. Org. Synth. 1985; 63: 183
• 10d Xu S, Held I, Kempf B, Mayr H, Steglich W, Zipse H. Chem. Eur. J. 2005; 11: 4751
• 11 Synthesis of Compound 17: To a solution of 9 (15.7 mg, 68.0 μmol) in CH₂Cl₂ (1 mL) were added DMAP (0.64 mg, 5.26 μmol) and 16 (20.0 mg, 53.0 μmol). Then the solution was cooled to 0 °C and DCC (11.9 mg, 58.0 μmol) was added. The mixture was stirred at 0 °C for 10 min, then at r.t. overnight. The precipitate was filtered off and the filtrate was evaporated to dryness. The residue was diluted in CH₂Cl₂ (5 mL) and washed once with 0.5 M HCl solution (2 mL) and once with sat. aq NaHCO₃ solution. After drying with MgSO₄ the product was purified by flash chromatography (petroleum ether–Et₂O 1:1; silica gel, R_f 0.13 and 0.08) to yield 17 (27.0 mg, 46.0 μmol, 87.0%). Specifications for one THP-diastereomer: ¹H NMR (500 MHz, CDCl₃): δ = 9.45 (s, 1 H, H-12), 7.10 (br d, J = 6.6 Hz, 1 H, H-7), 5.34 (s, 1 H, H-11), 5.25–5.31 (m, 1 H, H-2), 5.08 (br s, 1 H, H-1′′), 4.75 (br t, J = 6.2 Hz, 1 H, H-2′), 4.70 (br s, 1 H, H-1), 3.88 (br s, 1 H, H-9), 3.82–3.88 (m, 1 H, H-5′′_ax), 3.56–3.61 (m, 1 H, H-5′′_eq), 2.75 (d, J = 4.1 Hz, 1 H, OH), 2.42–2.50 (m, 1 H, H-6_ax), 2.20–2.30 (m, 1 H, H-6_eq), 2.09 (s, 3 H, H-12′), 2.01–2.09 (m, 1 H, H-3_ax), 1.49–1.85 (m, 10 H, H-3_eq, H-3′, H-2′′, H-3′′, H-4′′), 1.37–1.45 (m, 2 H, H-4′), 1.34 (s, 3 H, H-14), 1.23–1.32 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.06 (s, 3 H, H-13), 0.88 (t, J = 7.1 Hz, 3 H, H-10′). ¹³C NMR (125 MHz, CDCl₃): δ = 192.9 (C-12), 175.4 (C-15), 171.1 (C-11′), 169.7 (C-1′), 154.3 (C-7), 138.3 (C-8), 103.8 (C-11), 99.2 (C-1′′), 73.4 (C-2′), 71.4 (C-2), 67.4 (C-1), 61.6 (C-5′′), 52.7 (C-10), 46.6 (C-9), 39.5 (C-5), 37.4 (C-3), 33.5 (C-4), 33.4 (C-13), 31.8 (C-3′), 30.7 (C-8′), 29.7 (C-2′′), 29.3 (C-5′), 29.13 (C-6′), 29.11 (C-7′), 25.1 (C-4′), 24.9 (C-4′′), 24.6 (C-6), 23.3 (C-14), 22.6 (C-9′), 20.5 (C-12′), 18.1 (C-3′′), 14.1 (C-10′). [α]²⁰ _D –45.5 (CHCl₃, c = 0.2). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₃₂H₄₈O₁₀Na: 615.3146; found: 615.3157.
• 12a Askin D, Angst C, Danishefsky S. J. Org. Chem. 1987; 52: 622
• 12b Prazeres VF. V, Castedo L, González-Bello C. Eur. J. Org. Chem. 2008; 3991
• 13 Baars SM, Hoberg JO. Carbohydr. Res. 2006; 341: 1680
• 14 Synthesis of Compound 21: Compound 10 (21.8 mg, 79.0 μmol) was diluted in toluene (900 μL). 2,4,6-Trichlorobenzoyl chloride (10.4 μL, 67.0 μmol) and Et₃N (17.0 μL, 121 μmol) were added and the solution was stirred for 2 h at r.t. After this a mixture of 20 (30 mg, 61.0 μmol) and DMAP (9.6 mg, 79 μmol) in toluene (900 μL) was added and the solution was stirred for 24 h at r.t.. Sat. aq NaHCO₃ solution was added and extraction with EtOAc, drying over MgSO₄, filtration and evaporation afforded a yellow oil, which was purified by flash chromatography (petroleum ether–Et₂O, 1:1; silica gel, R_f 0.13 and 0.09). Yield: 31 mg (41.0 μmol, 67.9%). Specifications for one THP-diastereomer (R_f 0.09): ¹H NMR (500 MHz, CDCl₃): δ = 9.43 (s, 1 H, H-12), 7.11 (br d, J = 6.4 Hz, 1 H, H-7), 5.86 (br s, 1 H, H-1), 5.31 (s, 1 H, H-11), 5.05 (br s, 1 H, H-1′′), 4.75 (s, 2 H, H-11′), 4.36 (ddd, J = 12.8, 4.1, 2.4 Hz, 1 H, H-2), 4.22 (dd, J = 7.5, 5.0 Hz, 1 H, H-2′), 3.81–3.91 (m, 1 H, H-5′′_ax), 3.76 (ddd, J = 11.0, 6.3, 3.2 Hz, 1 H, H-12′_a), 3.67 (ddd, J = 11.0, 5.6, 3.2 Hz, 1 H, H-12′_b), 3.48–3.63 (m, 3 H, H-5′′_eq), 3.38 (s, 3 H, H-14′), 3.22 (br s, 1 H, H-9), 2.48 (ddd, J = 19.1, 5.8, 3.0 Hz, 1 H, H-6_ax), 2.18–2.29 (m, 1 H, H-6_eq), 1.99–2.12 (m, 1 H, H-3′′_ax), 1.38–1.85 (m, 12 H, H-3, H-5, H-3′, H-4′, H-2′′, H-3′′_eq, H-4′′), 1.31 (s, 3 H, H-14), 1.21–1.31 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.05 (s, 3 H, H-13), 0.86–0.90 (m, 3 H, H-10′), 0.86 (s, 9 H, t-Bu), 0.07 (s, 3 H, SiMe), 0.05 (s, 3 H, SiMe). ¹³C NMR (125 MHz, CDCl₃): δ = 192.4 (C-12), 175.2 (C-15), 170.7 (C-1′), 154.2 (C-7), 137.9 (C-8), 103.8 (C-11), 99.6 (C-1′′), 95.0 (C-11′), 75.4 (C-2′), 72.7 (C-1), 71.6 (C-13′), 67.6 (C-12′), 65.9 (C-2), 61.4 (C-5′′), 59.0 (C-14′), 52.2 (C-10), 47.4 (C-9), 43.0 (C-3), 40.7 (C-5), 33.6 (C-13), 33.5 (C-4), 33.2 (C-3′), 31.9 (C-8′), 29.5 (C-2′′), 29.33 (C-5′), 29.31 (C-6′), 29.25 (C-7′), 25.8 (t-Bu), 25.07 (C-4′), 25.05 (C-4′′), 24.7 (C-6), 23.5 (C-14), 22.6 (C-9′), 18.3 (t-Bu), 17.6 (C-3′′), 14.1 (C-10′), –5.1 (SiMe), –5.3 (SiMe). [α]²⁰ _D –25.3 (CHCl₃, c = 0.3). HRMS (ESI⁺): m/z [M + Na]⁺ calcd. for C₄₀H₆₈O₁₁SiNa: 775.4423; found: 775.4400.
• 15a Trost BM, Caldwell CG, Murayama E, Heissler D. J. Org. Chem. 1983; 48: 3252
• 15b Carreira EM, Bois JD. J. Am. Chem. Soc. 1995; 117: 8106
• 16 Cleavage of the Silyl Protection Group in 21: Compound 21 (30.0 mg, 40.0 μmol) was diluted in HF·pyridine (1.14 mL, 1.59 mmol) in THF–pyridine prepared according to a procedure of Trost’s (see ref. 15a). The solution was stirred at r.t. for 24 h. Sat. aq NaHCO₃ solution was added. Extraction with EtOAc, drying over MgSO₄, filtration and evaporation afforded a yellow oil, which was purified by flash chromatography (petroleum ether–acetone, 5:1; silica gel, R_f 0.12). Yield: 20.0 mg (31.0 μmol, 79.0%). Specifications for one THP-diastereomer: ¹H NMR (500 MHz, CDCl₃): δ = 9.47 (s, 1 H, H-12), 7.11 (d, J = 6.5 Hz, 1 H, H-7), 5.76 (s, 1 H, H-1), 5.40 (s, 1 H, H-11), 4.96 (br s, 1 H, H-1′′), 4.67–4.77 (m, 2 H, H-11′), 4.29–4.39 (m, 1 H, H-2), 4.21–4.28 (m, 1 H, H-2′), 3.93 (dd, J = 11.4, 2.5 Hz, 1 H, H-5′′_ax), 3.69–3.77 (m, 1 H, H-12′_a), 3.56–3.62 (m, 1 H, H-12′_b), 3.53–3.56 (m, 1 H, H-5′′_eq), 3.45–3.50 (m, 2 H, H-13′), 3.32 (s, 3 H, H-14′), 3.30 (br s, 1 H, H-9), 2.44 (dm, J = 19.3 Hz, 1 H, H-6_ax), 2.14–2.26 (m, 1 H, H-6_eq), 1.82 (d, J = 3.3 Hz, 1 H, OH), 1.66–1.77 (m, 4 H, H-3′, H-2′′), 1.47–1.65 (m, 7 H, H-3, H-5, H-3′′, H-4′′), 1.33–1.44 (m, 2 H, H-4′), 1.24 (s, 3 H, H-14), 1.16–1.27 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.00 (s, 3 H, H-13), 0.81 (t, J = 7.0 Hz, 3 H, H-10′). ¹³C NMR (125 MHz, CDCl₃): δ = 192.2 (C-12), 175.0 (C-15), 172.2 (C-1′), 153.8 (C-7), 137.8 (C-8), 99.9 (C-11), 94.9 (C-11′), 94.4 (C-1′′), 75.4 (C-2′), 72.9 (C-1), 71.7 (C-13′), 67.6 (C-12′), 65.7 (C-2), 61.2 (C-5′′), 59.0 (C-14′), 52.3 (C-10), 45.9 (C-9), 41.6 (C-5), 41.1 (C-3), 33.6 (C-13), 33.5 (C-4), 33.0 (C-3′), 31.9 (C-8′), 29.8 (C-2′′), 29.4 (C-5′), 29.3 (C-6′), 29.2 (C-7′), 25.1 (C-4′), 25.0 (C-4′′), 24.7 (C-6), 23.4 (C-14), 22.6 (C-9′), 17.5 (C-3′′), 14.1 (C-10′). [α]²⁰ _D –32.1 (CHCl₃, c = 1.2). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₃₄H₅₄O₁₁Na: 661.3564; found: 661.3549.
• 17 Mniopetal A (1a): ¹H NMR (500 MHz, CDCl₃): δ = 9.44 (s, 1 H, H-12), 7.12 (br d, J = 6.7 Hz, 1 H, H-7), 5.48 (br s, 1 H, H-11), 5.37 (ddd, J = 12.7, 4.0, 2.3 Hz, 1 H, H-2), 4.87 (dd, J = 6.5, 6.5 Hz, 1 H, H-2′), 4.59 (br s, 1 H, H-1), 3.89 (br s, 1 H, H-9), 2.46 (dm, J = 19.5 Hz, 1 H, H-6_ax), 2.24 (dm, J = 19.5 Hz, 1 H, H-6_eq), 2.14 (s, 3 H, H-12′), 2.08 (dd, J = 12.6, 12.6 Hz, 1 H, H-3_ax), 1.81–1.85 (m, 2 H, H-3′), 1.77 (dd, J = 12.7, 3.4 Hz, 1 H, H-5), 1.50 (dd, J = 12.2, 3.6 Hz, 1 H, H-3_eq), 1.37–1.44 (m, 2 H, H-4′), 1.33 (s, 3 H, H-14), 1.20–1.30 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.05 (s, 3 H, H-13), 0.88 (t, J = 7.1 Hz, 3 H, H-10′). ¹³C NMR (125 MHz, CDCl₃): δ = 193.3 (C-12), 175.9 (C-15), 171.7 (C-11′), 169.6 (C-1′), 154.8 (C-7), 138.5 (C-8), 99.6 (C-11), 73.0 (C-2′), 71.1 (C-2), 68.1 (C-1), 53.4 (C-10), 46.2 (C-9), 39.7 (C-5), 37.5 (C-3), 33.6 (C-4), 33.3 (C-13), 31.8 (C-8′), 30.9 (C-3′), 29.3 (C-5′), 29.14 (C-6′), 29.11 (C-7′), 25.1 (C-4′), 24.7 (C-6), 23.3 (C-14), 22.6 (C-9′), 20.7 (C-12′), 14.1 (C-10′). [α]²⁰ _D –64.0 (CHCl₃, c = 0.4); Lit.^1b [α]²⁰ _D –63 (CHCl₃, c = 0.05). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₇H₄₀O₉Na: 531.2570; found: 531.2563. Mniopetal B (1b): ¹H NMR (500 MHz, CDCl₃): δ = 9.46 (s, 1 H, H-12), 7.18 (br d, J = 6.5 Hz, 1 H, H-7), 5.52 (br s, 1 H, H-11), 5.40 (ddd, J = 12.6, 4.0, 2.4 Hz, 1 H, H-2), 4.56 (br s, 1 H, H-1), 4.49 (br s, 1 H, OH), 4.18 (br s, 1 H, H-2′), 3.85 (br s, 1 H, H-9), 2.99 (br s, 1 H, OH), 2.92 (br s, 1 H, OH), 2.49 (dddm, J = 19.5, 6.7, 3.9 Hz, 1 H, H-6_ax), 2.26 (ddm, J = 19.5, 12.9 Hz, 1 H, H-6_eq), 2.02 (ddd, J = 12.6, 12.6, 6.7 Hz, 1 H, H-3_ax), 1.77 (dd, J = 12.6, 3.3 Hz, 1 H, H-5), 1.68–1.74 (m, 1 H, H-3′_a), 1.62–1.67 (m, 1 H, H-3′_b), 1.55–1.59 (m, 1 H, H-3_eq), 1.37-1.43 (m, 2 H, H-4′), 1.35 (s, 3 H, H-14), 1.20–1.30 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.07 (s, 3 H, H-13), 0.88 (t, J = 6.8 Hz, 3 H, H-10′). ¹³C NMR (125 MHz, CDCl₃): δ = 193.2 (C-12), 175.7 (C-15), 174.4 (C-1′), 154.9 (C-7), 138.1 (C-8), 99.4 (C-11), 71.4 (C-2), 70.6 (C-2′), 68.8 (C-1), 53.4 (C-10), 46.2 (C-9), 39.6 (C-5), 37.4 (C-3), 34.5 (C-3′), 33.7 (C-4), 33.3 (C-13), 31.8 (C-8′), 29.4 (C-5′), 29.3 (C-6′), 29.2 (C-7′), 24.8 (C-4′), 24.7 (C-6), 23.2 (C-14), 22.7 (C-9′), 14.1 (C-10′). [α]²⁰ _D –47.3 (CHCl₃, c = 0.1); Lit.^1b [α]²⁰ _D –46 (CHCl₃, c = 0.05). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₅H₃₈O₈Na: 489.2465; found: 489.2475. Mniopetal C (1c): ¹H NMR (500 MHz, CDCl₃): δ = 9.44 (s, 1 H, H-12), 7.14 (br d, J = 6.8 Hz, 1 H, H-7), 5.51 (br s, 1 H, H-11), 5.38 (ddd, J = 12.7, 4.0, 2.3 Hz, 1 H, H-2), 4.56 (br s, 1 H, H-1), 4.18 (dd, J = 7.5, 4.1 Hz, 1 H, H-2′), 3.83 (br s, 1 H, H-9), 2.48 (ddd, J = 18.6, 6.0, 3.0 Hz, 1 H, H-6_ax), 2.25 (ddm, J = 19.0, 12.5 Hz, 1 H, H-6_eq), 2.04 (dd, J = 12.6, 12.6 Hz, 1 H, H-3_ax), 1.76 (dd, J = 12.2, 3.9 Hz, 1 H, H-5), 1.69–1.75 (m, 1 H, H-3′_a), 1.63–1.68 (m, 1 H, H-3′_b), 1.55 (dd, J = 12.3, 4.2 Hz, 1 H, H-3_eq), 1.38–1.44 (m, 2 H, H-4′), 1.34 (s, 3 H, H-14), 1.24–1.33 (m, 6 H, H-5′, H-6′, H-7′), 1.06 (s, 3 H, H-13), 0.88 (t, J = 6.8 Hz, 3 H, H-8′). ¹³C NMR (125 MHz, CDCl₃): δ = 194.3 (C-12), 175.9 (C-15), 174.4 (C-1′), 155.1 (C-7), 135.2 (C-8), 99.5 (C-11), 71.3 (C-2), 70.7 (C-2′), 68.6 (C-1), 53.5 (C-10), 46.2 (C-9), 39.6 (C-5), 37.4 (C-3), 34.4 (C-3′), 33.7 (C-4), 33.2 (C-13), 31.6 (C-6′), 28.9 (C-5′), 24.8 (C-4′), 24.7 (C-6), 23.2 (C-14), 22.5 (C-7′), 14.0 (C-8′). [α]²⁰ _D –47.3 (CHCl₃, c = 0.1); Lit.^1b [α]²⁰ _D –45 (CHCl₃, c = 0.05). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₃H₃₄O₈Na: 461.2152; found: 461.2150. Mniopetal D (1d): ¹H NMR (500 MHz, CDCl₃): δ = 9.46 (s, 1 H, H-12), 7.16 (br d, J = 6.6 Hz, 1 H, H-7), 5.84 (br s, 1 H, H-1), 5.50 (s, 1 H, H-11), 4.49 (s, 1 H, OH), 4.39–4.44 (m, 1 H, H-2), 4.29–4.33 (m, 1 H, H-2′), 3.27 (br s, 1 H, H-9), 2.75 (d, J = 5.7 Hz, 1 H, OH), 2.52 (ddd, J = 19.6, 6.7, 3.3 Hz, 1 H, H-6_ax), 2.27 (ddd, J = 19.7, 12.8, 2.5 Hz, 1 H, H-6_eq), 1.95 (d, J = 2.8 Hz, 1 H, OH), 1.80–1.88 (m, 1 H, H-3′_a), 1.57–1.73 (m, 4 H, H-3, H-5, H-3′_b), 1.44–1.54 (m, 2 H, H-4′), 1.32 (s, 3 H, H-14), 1.23–1.30 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.08 (s, 3 H, H-13), 0.87 (t, J = 7.1 Hz, 3 H, H-10′). ¹³C NMR (125 MHz, CDCl₃): δ = 192.6 (C-12), 176.1 (C-15), 174.4 (C-1′), 154.6 (C-7), 137.5 (C-8), 99.3 (C-11), 74.5 (C-1), 70.6 (C-2′), 65.2 (C-2), 52.3 (C-10), 47.0 (C-9), 41.3 (C-3), 40.8 (C-5), 34.6 (C-3′), 33.53 (C-4), 33.49 (C-13), 31.8 (C-8′), 29.4 (C-5′), 29.3 (C-6′), 29.1 (C-7′), 24.7 (C-6), 24.5 (C-4′), 23.4 (C-14), 22.6 (C-9′), 14.1 (C-10′). [α]²⁰ _D –36.6 (CHCl₃, c = 0.1); Lit.^1b [α]²⁰ _D –40 (CHCl₃, c = 0.05). HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₅H₃₈O₈Na: 489.2465; found: 489.2434.