Synthesis of Marine Oxylipins Constanolactones C and D

Jörg Pietruszka; Anja C. M. Rieche; Niklas Schöne

doi:10.1055/s-2007-986647

LETTER

Synthesis of Marine Oxylipins Constanolactones C and D

Jörg Pietruszka*, Anja C. M. Rieche, Niklas Schöne
Institut für Bioorganische Chemie, Heinrich-Heine-Universität Düsseldorf, Forschungszentrum Jülich, Stetternicher Forst Geb. 15.8, 52428 Jülich, Germany
Fax: +49(2461)616196; e-Mail: j.pietruszka@fz-juelich.de;

Abstract

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Abstract

After providing the marine oxylipins constanolactones A and B, the next two members of this family were synthesized for the first time. Key to the success was a highly enantioselective and Z-selective reagent-controlled allyl addition (>99%) en route to the aliphatic side chain.

Key words

allylation - asymmetric synthesis - boron - natural products - total synthesis

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Referenzen

References and Notes

For isolation and structure elucidation, see:

<A NAME="RD22107ST-1A">1a</A> Nagle DG. Gerwick WH. Tetrahedron Lett. 1990, 31: 2995

<A NAME="RD22107ST-1B">1b</A> Nagle DG. Gerwick WH. J. Org. Chem. 1994, 59: 7227

For complete total syntheses of constanolactones A and B, see:

<A NAME="RD22107ST-1C">1c</A> White JD. Jensen MS. J. Am. Chem. Soc. 1995, 117: 6224

<A NAME="RD22107ST-1D">1d</A> Barloy-Da Silva C. Benkouider A. Pale P. Tetrahedron Lett. 2000, 41: 3077

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<A NAME="RD22107ST-1F">1f</A> Pietruszka J. Wilhelm T. Synlett 2003, 1698

Constanolactone E:

<A NAME="RD22107ST-1G">1g</A> Miyaoka H. Shigemoto T. Yamada Y. Tetrahedron Lett. 1996, 37: 7407

<A NAME="RD22107ST-1H">1h</A> Miyaoka H. Shigemoto T. Tamura M. Yamada Y. Heterocycles 1998, 40: 205

<A NAME="RD22107ST-1I">1i</A> Miyaoka H. Shigemoto T. Yamada Y. Heterocycles 1998, 47: 415

<A NAME="RD22107ST-2A">2a</A> For isolation and structure elucidation: Seo Y. Cho KW. Rho J.-R. Shin J. Kwon B.-M. Bok S.-H. Song J.-I. Tetrahedron 1996, 52: 10583

For a complete total synthesis of solandelactone E (and structure revision), see:

<A NAME="RD22107ST-2C">2c</A> Davoren JE. Martin SF. J. Am. Chem. Soc. 2007, 129: 510

For isolation and structure elucidation, see:

<A NAME="RD22107ST-3A">3a</A> Niwa H. Wakamatsu K. Yamada K. Tetrahedron Lett. 1989, 30: 4543

<A NAME="RD22107ST-3B">3b</A> Kigoshi H. Niwa H. Yamada K. Stout TJ. Clardy J. Tetrahedron Lett. 1991, 32: 2427

For a completed syntheses of halicholactone, see:

<A NAME="RD22107ST-3C">3c</A> Critcher DJ. Connolly S. Wills M. Tetrahedron Lett. 1995, 36: 3763

<A NAME="RD22107ST-3D">3d</A> Critcher DJ. Connolly S. Wills M. J. Org. Chem. 1997, 62: 6638

<A NAME="RD22107ST-3E">3e</A> Takemoto Y. Baba Y. Saha G. Nakao S. Iwata C. Tanaka T. Ibuka T. Tetrahedron Lett. 2000, 41: 3653

<A NAME="RD22107ST-3F">3f</A> Baba Y. Saha G. Nakao S. Iwata C. Tanaka T. Ibuka T. Ohishi H. Takemoto Y. J. Org. Chem. 2001, 66: 81

<A NAME="RD22107ST-3G">3g</A> Takahashi T. Watanabe H. Kitahara T. Heterocycles 2002, 58: 99

For neohali-cholactone, see ref. 3c and 3d.

Reviews:

<A NAME="RD22107ST-4A">4a</A> Gerwick WH. Chem. Rev. 1993, 93: 1807

<A NAME="RD22107ST-4B">4b</A> Gerwick WH. Nagle DG. Proteau PJ. Top. Curr. Chem. 1993, 167: 119

<A NAME="RD22107ST-5A">5a</A> Okude Y. Hirano S. Hiyama T. Nozaki H. J. Am. Chem. Soc. 1977, 99: 3179

<A NAME="RD22107ST-5B">5b</A> Hiyama T. Okude Y. Kimura K. Nozaki H. Bull. Chem. Soc. Jpn. 1982, 55: 561

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<A NAME="RD22107ST-5D">5d</A> Review: Fürstner A. Chem. Rev. 1999, 99: 991

<A NAME="RD22107ST-6">6</A> Enantiomerically pure cyclopropane building blocks were synthesized via a chemoenzymatic sequence: Pietruszka J. Rieche ACM. Wilhelm T. Witt A. Adv. Synth. Catal. 2003, 345: 1273

<A NAME="RD22107ST-7A">7a</A> Pietruszka J. Schöne N. Angew. Chem. Int. Ed. 2003, 42: 5638 ; Angew. Chem. 2003, 115, 5796

<A NAME="RD22107ST-7B">7b</A> Pietruszka J. Schöne N. Synthesis 2006, 24

<A NAME="RD22107ST-8">8</A> Smith AB. Fox RJ. Org. Lett. 2004, 6: 1477

<A NAME="RD22107ST-9">9</A> Hoffmann RW. Weidmann U. J. Organomet. Chem. 1980, 195: 137

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<A NAME="RD22107ST-10B">10b</A> Wavrin L. Viala J. Synthesis 2002, 326

<A NAME="RD22107ST-11">11</A> Nicolaou KC. Ramphal JY. Abe Y. Synthesis 1989, 898

<A NAME="RD22107ST-12">12</A> Takai K. Nitta K. Utimoto K. J. Am. Chem. Soc. 1986, 108: 7408

Spectroscopic data of 1c, 1d, 2, 4, 12 and 13:
Aldehyde 2: R _f 0.48 (EtOAc); [α]²⁰ _D +73.0 (c = 2.4, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.15 (ddd, ³ J _3a,1 = 8.4 Hz, ³ J _3a,2 = 6.4 Hz, ² J _3a,3b = 4.8 Hz, 1 H, 3-H_a), 1.37 (ddd, ³ J _3b,2 = 9.2 Hz, ³ J _3b,1 = 4.8 Hz, ² J _3b,3a = 4.8 Hz, 1 H, 3-H_b), 1.71 (dddd, ² J ₃ _′a,3 _′b = 13.8 Hz, ³ J ₃ _′a,4 _′a = 10.9 Hz, ³ J ₃ _′a,2 _′ = 10.6 Hz, ³ J ₃ _′a,4 _′b = 4.8 Hz, 1 H, 3′-H_a), 1.79 (dddd, ³ J _2,3b = 9.2 Hz, ³ J _2,2 _′ = 7.2 Hz, ³ J _2,3a = 6.4 Hz, ³ J _2,1 = 4.0 Hz, 1 H, 2-H), 1.85 (ddddd, ³ J ₄ _′a,3 _′a = 10.9 Hz, ² J ₄ _′a,4 _′b = 9.9 Hz, ³ J ₄ _′a,5 _′a = 9.1 Hz, ³ J ₄ _′a,5 _′b = 7.0 Hz, ³ J ₄ _′a,3 _′b = 4.7 Hz, 1 H, 4′-H_a), 1.98 (ddddd, ² J ₄ _′b,4 _′a = 9.9 Hz, ³ J ₄ _′b,3 _′b = 8.1 Hz, ³ J ₄ _′b,5 _′a = 7.1 Hz, ³ J ₄ _′b,5 _′b = 4.8 Hz, ³ J ₄ _′b,3 _′a = 4.8 Hz, 1 H, 4′-H_b), 2.05 (ddddd, ² J ₃ _′b,3 _′a = 13.8 Hz, ³ J ₃ _′b,4 _′b = 8.1 Hz, ³ J ₃ _′b,4 _′a = 4.7 Hz, ³ J ₃ _′b,2 _′ = 3.4 Hz, ⁴ J ₃ _′b,5 _′b = 1.1 Hz, 1 H, 3′-H_b), 2.11 (dddd, ³ J _1,3a = 8.4 Hz, ³ J _1,3b = 4.8 Hz, ³ J _1,2 = 4.0 Hz, ³ J _1,CHO = 4.0 Hz, 1 H, 1-H), 2.48 (dddd, ² J ₅ _′a,5 _′b = 17.8 Hz, ³ J ₅ _′a,4 _′a = 9.1 Hz, ³ J ₅ _′a,4 _′b = 7.1 Hz, ⁴ J ₅ _′a,3 = 0.9 Hz, 1 H, 5′-H_a), 2.60 (dddd, ² J ₅ _′b,5 _′a = 17.8 Hz, ³ J ₅ _′b,4 _′a = 7.0 Hz, ³ J ₅ _′b,4 _′b = 4.8 Hz, ⁴ J ₅ _′b,3 _′b = 1.1 Hz, 1 H, 5′-H_b), 3.90 (ddd, ³ J ₂ _′,3 _′a = 10.6 Hz, ³ J ₂ _′,2 = 7.2 Hz, ³ J ₂ _′,3 _′b = 3.4 Hz, 1 H, 2′-H), 9.38 (d, ³ J _CHO,1 = 4.0 Hz, 1 H, CHO). ¹³C NMR (151 MHz, CDCl₃): δ = 11.9 (C-3), 18.4 (C-4′), 26.8 (C-2), 26.9 (C-1), 28.0 (C-3′), 29.5 (C-5′), 80.8 (C-2′), 170.7 (C-6′), 199.8 (CHO). HRMS (ESI, 70 eV): m/z calcd for C₉H₁₂O₃: 168.0786; found: 168.0790.
Iodide 4: R _f 0.19 (PE-EtOAc, 90:10); [α]²⁰ _D -25 (c = 0.90, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.98 (t, ³ J _11,10 = 7.5 Hz, 3 H, 11-H), 1.81 (d, ³ J _OH,3 = 4.3 Hz, 1 H, OH), 2.07 (qddt, ³ J _10,11 = 7.5 Hz, ³ J _10,9 = 7.2 Hz, ⁴ J _10,8 = 1.6 Hz, ⁵ J _10,7 = 0.8 Hz, 2 H, 10-H), 2.34 (m_c, 2 H, 4-H), 2.80 (ddddtt, ³ J _7,6 = 7.4 Hz, ³ J _7,8 = 7.2 Hz, ⁴ J _7,9 = 1.7 Hz, ⁴ J _7,5 = 1.7 Hz, ⁵ J _7,10 = 0.8 Hz, ⁵ J _7,4 = 0.8 Hz, 2 H, 7-H), 4.15 (m_c, 1 H, 3-H), 5.29 (dtt, ³ J _8,9 = 10.6 Hz, ³ J _8,7 = 7.2 Hz, ⁴ J _8,10 = 1.6 Hz, 1 H, 8-H), 5.39 (dtt, ³ J _5,6 = 10.8 Hz, ³ J _5,4 = 7.5 Hz, ⁴ J _5,7 = 1.7 Hz, 1 H, 5-H), 5.42 (dtt, ³ J _9,8 = 10.6 Hz, ³ J _9,10 = 7.2 Hz, ⁴ J _9,7 = 1.7 Hz, 1 H, 9-H), 5.59 (dtt, ³ J _6,5 = 10.8 Hz, ³ J _6,7 = 7.4 Hz, ⁴ J _6,4 = 1.6 Hz, 1 H, 6-H), 6.38 (dd, ³ J _1,2 = 14.5 Hz, ⁴ J _1,3 = 1.4 Hz, 1 H, 1-H), 6.60 (dd, ³ J _2,1 = 14.5 Hz, ³ J _2,3 = 5.9 Hz, 1 H, 2-H). ¹³C NMR (151 MHz, CDCl₃): δ = 14.2 (C-11), 20.6 (C-10), 25.7 (C-7), 34.6 (C-4), 73.8 (C-3), 77.3 (C-1), 123.6 (C-5), 126.5 (C-8), 132.4 (C-9), 132.5 (C-6), 147.7 (C-2). GC-MS (EI, +ve ions): m/z (%) = 274(1) [M - H₂O]⁺, 183 (100) [C₃H₄IO⁺].
Constanolactone C (1c): R _f 0.22 (EtOAc); separation of the diastereomers 1c and 1d with semi-preparative HPLC (Maxsil 5 µm, 250 × 10 mm; c = 6.4 mg/mL; flow = 3 mL/min; λ = 202 nm); [α]²⁰ _D -5.8 (c = 0.70, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.62 (ddd, ³ J _7a,8 = 8.6 Hz, ² J _7a,7b = 5.2 Hz, ³ J _7a,6 = 5.2 Hz, 1 H, 7-H_a), 0.75 (ddd, ³ J _7b,6 = 8.8 Hz, ³ J _7b,8 = 5.6 Hz, ² J _7b,7a = 5.2 Hz, 1 H, 7-H_b), 0.97 (t, ³ J _20,19 = 7.5 Hz, 3 H, 20-H), 1.00 (dddd, ³ J _6,7b = 8.8 Hz, ³ J _6,5 = 8.4 Hz, ³ J _6,7a = 5.2 Hz, ³ J _6,8 = 4.4 Hz, 1 H, 6-H), 1.15 (dddd, ³ J _8,7a = 8.6 Hz, ³ J _8,9 = 7.4 Hz, ³ J _8,7b = 5.6 Hz, ³ J _8,6 = 4.4 Hz, 1 H, 8-H), 1.67 (dddd, ² J _4a,4b = 13.9 Hz, ³ J _4a,3a = 10.6 Hz, ³ J _4a,5 = 10.1 Hz, ³ J _4a,3b = 4.9 Hz, 1 H, 4-H_a) 1.80 (ddddd, ² J _3a,3b = 13.6 Hz, ³ J _3a,4a = 10.6 Hz, ³ J _3a,2a = 8.7 Hz, ³ J _3a,2b = 7.1 Hz, ³ J _3a,4b = 4.8 Hz, 1 H, 3-H_a), 1.74 (br, 2 H, OH), 1.95 (ddddd, ² J _3b,3a = 13.6 Hz, ³ J _3b,2a = 7.0 Hz, ³ J _3b,2b = 5.3 Hz, ³ J _3b,4b = 5.1 Hz, ³ J _3b,4a = 4.9 Hz, 1 H, 3-H_b), 2.01 (ddddd, ² J _4b,4a = 13.9 Hz, ³ J _4b,3b = 5.1 Hz, ³ J _4b,3a = 4.8 Hz, ³ J _4b,5 = 3.5 Hz, ⁵ J _4b,2b = 1.1 Hz, 1 H, 4-H_b), 2.07 (qddt, ³ J _19,20 = 7.5 Hz, ³ J _19,18 = 7.2 Hz, ⁴ J _19,17 = 1.6 Hz, ⁵ J _19,16 = 0.8 Hz, 2 H, 19-H), 2.33 (ddddt, ² J _13a,13b = 14.4 Hz, ³ J _13a,14 = 7.1 Hz, ³ J _13a,12 = 5.9 Hz, ⁴ J _13a,15 = 1.6 Hz, ⁵ J _13a,16 = 0.8 Hz, 1 H, 13-H_a), 2.38 (ddddt, ² J _13b,13a = 14.4 Hz, ³ J _13b,14 = 7.5 Hz, ³ J _13b,12 = 6.9 Hz, ⁴ J _13b,15 = 1.5 Hz, ⁵ J _13b,16 = 0.8 Hz, 1 H, 13-H_b), 2.45 (ddd, ² J _2a,2b = 17.8 Hz, ³ J _2a,3a = 8.7 Hz, ³ J _2a,3b = 7.0 Hz, 1 H, 2-H_a), 2.56 (dddd, ² J _2b,2a = 17.8 Hz, ³ J _2b,3a = 7.1 Hz, ³ J _2b,3b = 5.3 Hz, ⁵ J _2b,4b = 1.1 Hz, 1 H, 2-H_b), 2.81 (ddddtdd, ³ J _16,15 = 7.3 Hz, ³ J _16,17 = 7.3 Hz, ⁴ J _16,18 = 1.6 Hz, ⁴ J _16,14 = 1.6 Hz, ⁵ J _16,19 = 0.8 Hz, ⁵ J _16,13a = 0.8 Hz, ⁵ J _16,13b = 0.8 Hz, 2 H, 16-H), 3.70-3.74 (m, 1 H, 9-H), 3.72 (ddd, ³ J _5,4a = 10.1 Hz, ³ J _5,6 = 8.4 Hz, ³ J _5,4b = 3.5 Hz, 1 H, 5-H), 4.20 (m_c, 1 H, 12-H), 5.30 (dtt, ³ J _17,18 = 10.6 Hz, ³ J _17,16 = 7.2 Hz, ⁴ J _17,19 = 1.6 Hz, 1 H, 17-H), 5.40 (dtt, ³ J _18,17 = 10.6 Hz, ³ J _18,19 = 7.2 Hz, ⁴ J _18,16 = 1.6 Hz, 1 H, 18-H), 5.43 (dtt, ³ J _14,15 = 10.7 Hz, ³ J _14,13 = 7.3 Hz, ⁴ J _14,16 = 1.6 Hz, 1 H, 14-H), 5.53 (dtdd, ³ J _15,14 = 10.7 Hz, ³ J _15,16 = 7.3 Hz, ⁴ J _15,13a = 1.6 Hz, ⁴ J _15,13b = 1.5 Hz, 1 H, 15-H), 5.79 (m_c, 2 H, 10-H, 11-H). ¹³C NMR (151 MHz, CDCl₃): δ = 7.5 (C-7), 14.2 (C-20), 18.3 (C-3), 20.4 (C-6), 20.6 (C-19), 23.4 (C-8), 25.7 (C-16), 27.8 (C-4), 29.5 (C-2), 35.0 (C-13), 71.6 (C-12), 74.2 (C-9), 83.6 (C-5), 124.8 (C-14), 126.9 (C-17), 131.3 (C-15), 132.0 (C-10), 132.2 (C-18), 133.6 (C-11), 171.5 (C-1). HRMS (ESI, +ve ions, solution in MeOH): m/z calcd for C₂₀H₃₀NaO₄: 357.2036; found: 357.2024.
Constanolactone D (1d): R _f 0.22 (EtOAc); [α]²⁰ _D -9.1 (c = 0.60, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.59 (ddd, ³ J _7a,8 = 8.8 Hz, ³ J _7a,6 = 5.3 Hz, ² J _7a,7b = 5.3 Hz, 1 H, 7-H_a), 0.64 (ddd, ³ J _7b,6 = 8.7 Hz, ³ J _7b,8 = 5.5 Hz, ² J _7b,7a = 5.3 Hz, 1 H, 7-H_b), 0.97 (t, ³ J _20,19 = 7.5 Hz, 3 H, 20-H), 1.11 (dddd, ³ J _6,7b = 8.7 Hz, ³ J _6,5 = 8.1 Hz, ³ J _6,7a = 5.3 Hz, ³ J _6,8 = 4.4 Hz, 1 H, 6-H), 1.14 (dddd, ³ J _8,7a = 8.8 Hz, ³ J _8,9 = 7.3 Hz, ³ J _8,7b = 5.5 Hz, ³ J _8,6 = 4.4 Hz, 1 H, 8-H), 1.69 (dddd, ² J _4a,4b = 13.9 Hz, ³ J _4a,3a = 10.9 Hz, ³ J _4a,5 = 10.5 Hz, ³ J _4a,3b = 5.1 Hz, 1 H, 4-H_a), 1.81 (ddddd, ² J _3a,3b = 13.6 Hz, ³ J _3a,4a = 10.9 Hz, ³ J _3a,2a = 8.8 Hz, ³ J _3a,2b = 7.1 Hz, ³ J _3a,4b = 5.0 Hz, 1 H, 3-H_a), 1.87 (br, 2 H, OH), 1.96 (ddddd, ² J _3b,3a = 13.6 Hz, ³ J _3b,2a = 7.1 Hz, ³ J _3b,2b = 5.2 Hz, ³ J _3b,4a = 5.1 Hz, ³ J _3b,4b = 4.8 Hz, 1 H, 3-H_b), 2.02 (ddddd, ² J _4b,4a = 13.9 Hz, ³ J _4b,3a = 5.0 Hz, ³ J _4b,3b = 4.8 Hz, ³ J _4b,5 = 3.3 Hz, ⁵ J _4b,2b = 1.2 Hz, 1 H, 4-H_b), 2.07 (qddt, ³ J _19,20 = 7.5 Hz, ³ J _19,18 = 7.3 Hz, ⁴ J _19,17 = 1.6 Hz, ⁵ J _19,16 = 0.7 Hz, 2 H, 19-H), 2.33 (ddddt, ² J _13a,13b = 14.3 Hz, ³ J _13a,14 = 7.1 Hz, ³ J _13a,12 = 5.7 Hz, ⁴ J _13a,15 = 1.6 Hz, ⁵ J _13a,16 = 0.7 Hz, 1 H, 13-H_a), 2.38 (ddddt, ² J _13b,13a = 14.3 Hz, ³ J _13b,12 = 7.6 Hz, ³ J _13b,14 = 7.1 Hz, ⁴ J _13b,15 = 1.6 Hz, ⁵ J _13b,16 = 0.5 Hz, 1 H, 13-H_b), 2.46 (ddd, ² J _2a,2b = 17.7 Hz, ³ J _2a,3a = 8.8 Hz, ³ J _2a,3b = 7.1 Hz, 1 H, 2-H_a), 2.57 (dddd, ² J _2b,2a = 17.7 Hz, ³ J _2b,3a = 7.1 Hz, ³ J _2b,3b = 5.2 Hz, ⁵ J _2b,4b = 1.2 Hz, 1 H, 2-H_b), 2.81 (ddddtdd, ³ J _16,15 = 7.4 Hz, ³ J _16,17 = 7.2 Hz, ⁴ J _16,14 = 1.7 Hz, ⁴ J _16,18 = 1.6 Hz, ⁵ J _16,19 = 0.7 Hz, ⁵ J _16,13a = 0.7 Hz, ⁵ J _16,13b = 0.5 Hz, 2 H, 16-H), 3.71 (m_c, 1 H, 9-H), 3.73 (ddd, ³ J _5,4a = 10.5 Hz, ³ J _5,6 = 8.1 Hz, ³ J _5,4b = 3.3 Hz, 1 H, 5-H), 4.19 (m_c, 1 H, 12-H), 5.30 (dtt, ³ J _17,18 = 10.6 Hz, ³ J _17,16 = 7.2 Hz, ⁴ J _17,19 = 1.6 Hz, 1 H, 17-H), 5.40 (dtt, ³ J _18,17 = 10.6 Hz, ³ J _18,19 = 7.3 Hz, ⁴ J _18,16 = 1.6 Hz, 1 H, 18-H), 5.42 (dddt, ³ J _14,15 = 10.8 Hz, ³ J _14,13b = 7.3 Hz, ³ J _14,13a = 7.1 Hz, ⁴ J _14,16 = 1.7 Hz, 1 H, 14-H), 5.55 (dtt, ³ J _15,14 = 10.8 Hz, ³ J _15,16 = 7.4 Hz, ⁴ J _15,13 = 1.6 Hz, 1 H, 15-H), 5.79 (m_c, 2 H, 10-H, 11-H). ¹³C NMR (151 MHz, CDCl₃): δ = 6.6 (C-7), 14.2 (C-20), 18.4 (C-3), 20.6 (C-19), 21.2 (C-8), 23.4 (C-6), 25.7 (C-16), 27.9 (C-4), 29.5 (C-2), 35.2 (C-13), 71.5 (C-12), 73.8 (C-9), 83.3 (C-5), 124.7 (C-14), 126.8 (C-17), 131.6 (C-15), 131.7 (C-10), 132.2 (C-18), 133.2 (C-11), 171.5 (C-1). HRMS (ESI, +ve ions, solution in MeOH): m/z calcd for C₂₀H₃₀NaO₄: 357.2036; found: 357.2024.
Acetate 12: R _f 0.34 (PE-EtOAc, 50:50); [α]²⁰ _D -7.5 (c = 0.70, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.63 (ddd, ³ J _7a,8 = 8.6 Hz, ³ J _7a,6 = 5.3 Hz, ² J _7a,7b = 5.3 Hz, 1 H, 7-H_a), 0.74 (ddd, ³ J _7b,6 = 8.9 Hz, ³ J _7b,8 = 5.5 Hz, ² J _7b,7a = 5.3 Hz, 1 H, 7-H_b), 0.97 (t, ³ J _20,19 = 7.5 Hz, 3 H, 20-H), 1.04 (dddd, ³ J _6,7b = 8.9 Hz, ³ J _6,5 = 7.5 Hz, ³ J _6,7a = 5.3 Hz, ³ J _6,8 = 4.4 Hz, 1 H, 6-H), 1.23 (dddd, ³ J _8,7a = 8.6 Hz, ³ J _8,9 = 8.1 Hz, ³ J _8,7b = 5.5 Hz, ³ J _8,6 = 4.4 Hz, 1 H, 8-H), 1.64 (dddd, ² J _4a,4b = 14.0 Hz, ³ J _4a,3a = 11.0 Hz, ³ J _4a,5 = 10.6 Hz, ³ J _4a,3b = 5.2 Hz, 1 H, 4-H_a), 1.81 (ddddd, ² J _3a,3b = 13.8 Hz, ³ J _3a,4a = 11.0 Hz, ³ J _3a,2a = 8.9 Hz, ³ J _3a,2b = 7.1 Hz, ³ J _3a,4b = 5.1 Hz, 1 H, 3-H_a), 1.93 (ddddd, ² J _3b,3a = 13.8 Hz, ³ J _3b,2a = 7.1 Hz, ³ J _3b,4a = 5.2 Hz, ³ J _3b,2b = 5.1 Hz, ³ J _3b,4b = 4.5 Hz, 1 H, 3-H_b), 1.98 (ddddd, ² J _4b,4a = 14.0 Hz, ³ J _4b,3a = 5.1 Hz, ³ J _4b,3b = 4.5 Hz, ³ J _4b,5 = 3.2 Hz, ⁴ J _4b,2b = 1.1 Hz, 1 H, 4-H_b), 2.07 (qddt, ³ J _19,20 = 7.5 Hz, ³ J _19,18 = 7.2 Hz, ⁴ J _19,17 = 1.6 Hz, ⁵ J _19,16 = 0.8 Hz, 2 H, 19-H), 2.07, 2.08 (2 × s, 6 H, 9-OAc, 12-OAc), 2.39 (ddddt, ² J _13a,13b = 14.6 Hz, ³ J _13a,14 = 7.1 Hz, ³ J _13a,12 = 6.3 Hz, ⁴ J _13a,15 = 1.6 Hz, ⁶ J _13a,16 = 0.8 Hz, 1 H, 13-H_a), 2.45 (ddd, ² J _2a,2b = 17.7 Hz, ³ J _2a,3a = 8.9 Hz, ³ J _2a,3b = 7.1 Hz, 1 H, 2-H_a), 2.46 (ddddt, ² J _13b,13a = 14.6 Hz, ³ J _13b,14 = 7.6 Hz, ³ J _13b,12 = 6.8 Hz, ⁴ J _13b,15 = 1.6 Hz, ⁵ J _13b,16 = 0.8 Hz, 1 H, 13-H_b), 2.56 (dddd, ² J _2b,2a = 17.7 Hz, ³ J _2b,3a = 7.1 Hz, ³ J _2b,3b = 5.1 Hz, ⁴ J _2b,4b = 1.1 Hz, 1 H, 2-H_b), 2.78 (ddddddd, ³ J _16,15 = 7.4 Hz, ³ J _16,17 = 7.3 Hz, ⁴ J _16,14 = 1.7 Hz, ⁴ J _16,18 = 1.6 Hz, ⁵ J _16,13a = 0.8 Hz, ⁵ J _16,13b = 0.8 Hz, ⁵ J _16,19a = 0.8 Hz, 2 H, 16-H), 3.80 (ddd, ³ J _5,4a = 10.6 Hz, ³ J _5,6 = 7.5 Hz, ³ J _5,4b = 3.2 Hz, 1 H, 5-H), 4.91 (dddd, ³ J _9,8 = 8.1 Hz, ³ J _9,10 = 5.8 Hz, ⁴ J _9,11 = 1.3 Hz, ⁵ J _9,12 = 0.7 Hz, 1 H, 9-H), 5.28 (dtt, ³ J _17,18 = 10.6 Hz, ³ J _17,16 = 7.3 Hz, ⁴ J _17,19 = 1.6 Hz, 1 H, 17-H), 5.30 (ddddd, ³ J _12,13b = 6.8 Hz, ³ J _12,13a = 6.3 Hz, ³ J _12,11 = 6.2 Hz, ⁴ J _12,10 = 1.2 Hz, ⁵ J _12,9 = 0.7 Hz, 1 H, 12-H), 5.34 (dddt, ³ J _14,15 = 10.7 Hz, ³ J _14,13b = 7.6 Hz, ³ J _14,134 = 7.1 Hz, ⁴ J _14,16 = 1.7 Hz, 1 H, 14-H), 5.39 (dtt, ³ J _18,17 = 10.6 Hz, ³ J _18,19 = 7.2 Hz, ⁴ J _18,16 = 1.6 Hz, 1 H, 18-H), 5.48 (dtt, ³ J _15,14 = 10.7 Hz, ³ J _15,16 = 7.4 Hz, ⁴ J _15,13 = 1.6 Hz, 1 H, 15-H), 5.70 (ddd, ³ J _10,11 = 15.7 Hz, ³ J _10,9 = 5.8 Hz, ⁴ J _10,12 = 1.2 Hz, 1 H, 10-H), 5.82 (ddd, ³ J _11,10 = 15.7 Hz, ³ J _11,12 = 6.2 Hz, ⁴ J _11,9 = 1.3 Hz, 1 H, 11-H). ¹³C NMR (151 MHz, CDCl₃): δ = 7.6 (C-7), 14.2 (C-20), 18.4 (C-3), 20.1 (C-8), 20.5 (C-19), 20.8 (C-6), 21.2, 21.3 (9-OAc, 12-OAc), 25.6 (C-16), 27.9 (C-4), 29.5 (C-2), 32.2 (C-13), 73.0 (C-12), 75.3 (C-9), 82.3 (C-5), 123.8 (C-14), 126.8 (C-17), 129.1 (C-10), 130.9 (C-11), 131.3 (C-15), 132.2 (C-18), 170.3, 170.3 (9-OAc, 12-OAc), 171.0 (C-1). HRMS (ESI, +ve ions, solution in MeOH): m/z calcd for C₂₄H₃₄NaO₆: 441.2248; found: 441.2242.
Acetate 13: R _f 0.34 (PE-EtOAc, 50:50); [α]²⁰ _D -4.4 (c = 0.50, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.59 (ddd, ³ J _7a,8 = 8.6 Hz, ³ J _7a,6 = 5.7 Hz, ² J _7a,7b = 5.4 Hz, 1 H, 7-H_a), 0.68 (ddd, ³ J _7b,6 = 8.7 Hz, ³ J _7b,8 = 5.4 Hz, ² J _7b,7a = 5.4 Hz, 1 H, 7-H_b), 0.98 (t, ³ J _20,19 = 7.5 Hz, 3 H, 20-H), 1.17-1.23 (m, 2 H, 6-H, 8-H), 1.64 (dddd, ² J _4a,4b = 13.7 Hz, ³ J _4a,3a = 10.6 Hz, ³ J _4a,5 = 10.1 Hz, ³ J _4a,3b = 5.0 Hz, 1 H, 4-H_a), 1.81 (ddddd, ² J _3a,3b = 13.6 Hz, ³ J _3a,4a = 10.6 Hz, ³ J _3a,2a = 8.7 Hz, ³ J _3a,2b = 7.1 Hz, ³ J _3a,4b = 4.9 Hz, 1 H, 3-H_a), 1.94 (ddddd, ² J _3b,3a = 13.6 Hz, ³ J _3b,2a = 7.0 Hz, ³ J _3b,2b = 5.3 Hz, ³ J _3b,4b = 5.1 Hz, ³ J _3b,4a = 5.0 Hz, 1 H, 3-H_b), 1.97 (ddddd, ² J _4b,4a = 13.7 Hz, ³ J _4b,3b = 5.1 Hz, ³ J _4b,3a = 4.9 Hz, ³ J _4b,5 = 3.3 Hz, ⁴ J _4b,2b = 1.2 Hz, 1 H, 4-H_b), 2.07 (qddt, ³ J _19,20 = 7.5 Hz, ³ J _19,18 = 7.2 Hz, ⁴ J _19,17 = 1.6 Hz, ⁵ J _19,16 = 0.8 Hz, 2 H, 19-H), 2.07, 2.09 (2 × s, 6 H, 9-OAc, 12-OAc), 2.36 (ddddt, ² J _13a,13b = 14.6 Hz, ³ J _13a,14 = 7.1 Hz, ³ J _13a,12 = 6.3 Hz, ⁴ J _13a,15 = 1.5 Hz, ⁶ J _13a,16 = 0.8 Hz, 1 H, 13-H_a), 2.45 (ddd, ² J _2a,2b = 17.7 Hz, ³ J _2a,3a = 8.7 Hz, ³ J _2a,3b = 7.0 Hz, 1 H, 2-H_a), 2.45 (ddddt, ² J _13b,13a = 14.6 Hz, ³ J _13b,14 = 7.5 Hz, ³ J _13b,12 = 6.8 Hz, ⁴ J _13b,15 = 1.6 Hz, ⁵ J _13b,16 = 0.8 Hz, 1 H, 13-H_b), 2.55 (dddd, ² J _2b,2a = 17.7 Hz, ³ J _2b,3a = 7.1 Hz, ³ J _2b,3b = 5.3 Hz, ⁴ J _2b,4b = 1.2 Hz, 1 H, 2-H_b), 2.78 (ddddddt, ³ J _16,15 = 7.3 Hz, ³ J _16,17 = 7.2 Hz, ⁴ J _16,14 = 1.7 Hz, ⁴ J _16,18 = 1.7 Hz, ⁵ J _16,13a = 0.8 Hz, ⁵ J _16,13b = 0.8 Hz, ⁵ J _16,19 = 0.8 Hz, 2 H, 16-H), 3.82 (ddd, ³ J _5,4a = 10.1 Hz, ³ J _5,6 = 6.8 Hz, ³ J _5,4b = 3.3 Hz, 1 H, 5-H), 4.83-4.87 (m, 1 H, 9-H), 5.28 (dtt, ³ J _17,18 = 10.6 Hz, ³ J _17,16 = 7.2 Hz, ⁴ J _17,19 = 1.6 Hz, 1 H, 17-H), 5.28 (m_c, 1 H, 12-H), 5.32 (dtt, ³ J _14,15 = 10.7 Hz, ³ J _14,13 = 7.3 Hz, ⁴ J _14,16 = 1.7 Hz, 1 H, 14-H), 5.40 (dtt, ³ J _18,17 = 10.6 Hz, ³ J _18,19 = 7.2 Hz, ⁴ J _18,16 = 1.7 Hz, 1 H, 18-H), 5.49 (dtt, ³ J _15,14 = 10.7 Hz, ³ J _15,16 = 7.3 Hz, ⁴ J _15,13 = 1.6 Hz, 1 H, 15-H), 5.68-5.74 (m, 2 H, 10-H, 11-H). ¹³C NMR (151 MHz, CDCl₃): δ = 6.7 (C-7), 14.2 (C-20), 18.3 (C-3), 20.3 (C-6, C-8), 20.6 (C-19), 21.2, 21.3 (9-OAc, 12-OAc), 21.7 (C-6, C-8), 25.7 (C-16), 27.8 (C-4), 29.5 (C-2), 32.3 (C-13), 73.0 (C-12), 75.5 (C-9), 81.9 (C-5), 123.7 (C-14), 126.7 (C-17), 129.5 (C-10, C-11), 130.5 (C-11, C-10), 131.4 (C-15), 132.2 (C-18), 170.1, 170.5 (9-OAc, 12-OAc), 171.1 (C-1). HRMS (ESI, +ve ions, solution in MeOH): m/z calcd C₂₄H₃₄NaO₆: 441.2248; found: 441.2253.