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DOI: 10.1055/s-2007-986647
Synthesis of Marine Oxylipins Constanolactones C and D
Publikationsverlauf
Publikationsdatum:
12. September 2007 (online)
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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
- For isolation and structure elucidation, see:
-
1a
Nagle DG.Gerwick WH. Tetrahedron Lett. 1990, 31: 2995 -
1b
Nagle DG.Gerwick WH. J. Org. Chem. 1994, 59: 7227 - For complete total syntheses of constanolactones A and B, see:
-
1c
White JD.Jensen MS. J. Am. Chem. Soc. 1995, 117: 6224 -
1d
Barloy-Da Silva C.Benkouider A.Pale P. Tetrahedron Lett. 2000, 41: 3077 -
1e
Yu J.Lai J.-Y.Ye J.Balu N.Reddy LM.Duan W.Fogel ER.Capdevila JH.Falck JR. Tetrahedron Lett. 2002, 43: 3939 -
1f
Pietruszka J.Wilhelm T. Synlett 2003, 1698 - Constanolactone E:
-
1g
Miyaoka H.Shigemoto T.Yamada Y. Tetrahedron Lett. 1996, 37: 7407 -
1h
Miyaoka H.Shigemoto T.Tamura M.Yamada Y. Heterocycles 1998, 40: 205 -
1i
Miyaoka H.Shigemoto T.Yamada Y. Heterocycles 1998, 47: 415 -
2a 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 -
2b
For a complete total synthesis of solandelactone E (and structure revision), see:
-
2c
Davoren JE.Martin SF. J. Am. Chem. Soc. 2007, 129: 510 - For isolation and structure elucidation, see:
-
3a
Niwa H.Wakamatsu K.Yamada K. Tetrahedron Lett. 1989, 30: 4543 -
3b
Kigoshi H.Niwa H.Yamada K.Stout TJ.Clardy J. Tetrahedron Lett. 1991, 32: 2427 - For a completed syntheses of halicholactone, see:
-
3c
Critcher DJ.Connolly S.Wills M. Tetrahedron Lett. 1995, 36: 3763 -
3d
Critcher DJ.Connolly S.Wills M. J. Org. Chem. 1997, 62: 6638 -
3e
Takemoto Y.Baba Y.Saha G.Nakao S.Iwata C.Tanaka T.Ibuka T. Tetrahedron Lett. 2000, 41: 3653 -
3f
Baba Y.Saha G.Nakao S.Iwata C.Tanaka T.Ibuka T.Ohishi H.Takemoto Y. J. Org. Chem. 2001, 66: 81 -
3g
Takahashi T.Watanabe H.Kitahara T. Heterocycles 2002, 58: 99 -
3h
For neohali-cholactone, see ref. 3c and 3d.
- Reviews:
-
4a
Gerwick WH. Chem. Rev. 1993, 93: 1807 -
4b
Gerwick WH.Nagle DG.Proteau PJ. Top. Curr. Chem. 1993, 167: 119 -
5a
Okude Y.Hirano S.Hiyama T.Nozaki H. J. Am. Chem. Soc. 1977, 99: 3179 -
5b
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5c
Takai K.Kimura K.Kuroda T.Hiyama T.Nozaki H. Tetrahedron Lett. 1983, 24: 5281 -
5d Review:
Fürstner A. Chem. Rev. 1999, 99: 991 - 6 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 -
7a
Pietruszka J.Schöne N. Angew. Chem. Int. Ed. 2003, 42: 5638 ; Angew. Chem. 2003, 115, 5796 -
7b
Pietruszka J.Schöne N. Synthesis 2006, 24 - 8
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Hoffmann RW.Weidmann U. J. Organomet. Chem. 1980, 195: 137 -
10a
Dess DB.Martin JC. J. Am. Chem. Soc. 1991, 113: 7277 -
10b
Wavrin L.Viala J. Synthesis 2002, 326 - 11
Nicolaou KC.Ramphal JY.Abe Y. Synthesis 1989, 898 - 12
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References and Notes
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-Ha), 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-Hb), 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′-Ha), 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′-Ha), 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′-Hb), 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′-Hb), 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′-Ha), 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′-Hb), 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 (mc, 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 (mc, 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-Ha), 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-Hb), 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-Ha) 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-Ha), 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-Hb), 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-Hb), 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-Ha), 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-Hb), 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-Ha), 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-Hb), 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 (mc, 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 (mc, 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-Ha), 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-Hb), 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-Ha), 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-Ha), 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-Hb), 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-Hb), 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-Ha), 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-Hb), 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-Ha), 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-Hb), 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 (mc, 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 (mc, 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 (mc, 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-Ha), 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-Hb), 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-Ha), 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-Ha), 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-Hb), 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-Hb), 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-Ha), 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-Ha), 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-Hb), 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-Hb), 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-Ha), 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-Hb), 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-Ha), 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-Ha), 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-Hb), 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-Hb), 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-Ha), 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-Ha), 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-Hb), 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-Hb), 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 (mc, 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.