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DOI: 10.1055/s-2003-40986
Total Synthesis of Marine OxylipinsConstanolactone A and B
Publication History
Publication Date:
05 August 2003 (online)
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Abstract
A short, high-yielding synthesis of the marine oxylipins constanolactoneA and B was reported. Starting from cinnamyl alcohol (3), the cylopropyl lactone moiety 2 was obtained in 28% yield (11steps). The second coupling partner, vinyl iodide 1,was isolated in 7 steps and 32% yield. Chromium mediatedaddition yielded the natural products as a 2:1 mixture (74%).
Key words
natural products - total synthesis - asymmetricsynthesis - cyclopropane - ozonolysis
- 1
Higgs MD.Mulheirn LJ. Tetrahedron Lett. 1981, 37: 4259 - 2
Seo Y.Cho KW.Rho J.-R.Shin J. Tetrahedron 1996, 52: 10583 -
3a
Niwa H.Wakamatsu K.Yamada K. Tetrahedron Lett. 1989, 30: 4543 -
3b
Kigoshi H.Niwa H.Yamada K.Stout TJ.Clardy J. TetrahedronLett. 1991, 32: 2427 -
4a
Nagle DG.Gerwick WH. Tetrahedron Lett. 1990, 31: 2995 -
4b
Nagle DG.Gerwick WH. J.Org. Chem. 1994, 59: 7227 - Completed syntheses: Halicholactone,see:
-
5a
Critcher DJ.Connolly S.Wills M. Tetrahedron Lett. 1995, 36: 3763 -
5b
Critcher DJ.Connolly S.Wills M. J. Org. Chem. 1997, 62: 6638 -
5c
Takemoto Y.Baba Y.Saha G.Nakao S.Iwata C.Tanaka T.Ibuka T. Tetrahedron Lett. 2000, 41: 3653 -
5d
Baba Y.Saha G.Nakao S.Iwata C.Tanaka T.Ibuka T.Ohishi H.Takemoto Y. J. Org.Chem. 2001, 66: 81 -
5e
Takahashi T.Watanabe H.Kitahara T. Heterocycles 2002, 58: 99 -
5f Neohalicholactone, seeref.5a,b. Constanolactone A and B, see:
White JD.Jensen MS. J.Am. Chem. Soc. 1995, 117: 6224 -
5g See also:
Barloy-DaSilva C.Benkouider A.Pale P. Tetrahedron Lett. 2000, 41: 3077 -
5h
Yu J.Lai J.-Y.Ye J.Balu N.Reddy LM.Duan W.Fogel ER.Capdevila JH.Falck JR. TetrahedronLett. 2002, 43: 3939 -
5i
Constanolactone E. see:Miyaoka H.Shigemoto T.Yamada Y. TetrahedronLett. 1996, 37: 7407 -
5j See further:
Miyaoka H.Shigemoto T.Yamada Y. Heterocycles 1998, 47: 415 -
5k Further synthetic approaches:
Critcher DJ.Connolly S.Mahon MF.Wills M. J.Chem. Soc., Chem. Commun. 1995, 139 -
5l
Barloy-Da Silva C.Pale P. Tetrahedron:Asymmetry 1998, 9: 3951 -
5m
Mohapatra DK.Datta A. J. Org. Chem. 1998, 63: 642 -
5n
Varadarajan S.Mohapatra DK.Datta A. TetrahedronLett. 1998, 39: 5667 -
5o
Varadarajan S.Mohapatra DK.Datta A. TetrahedronLett. 1998, 39: 1075 - 6
Gerwick WH. Chem.Rev. 1993, 93: 1807 - 7
Denmark SE.O’Connor SP. J. Org.Chem. 1997, 62: 3390 - 8
Pietruszka J.Wilhelm T.Witt A. Synlett 1999, 1981 - 9
Ley SV.Norman J.Griffith WP.Marsden SP. Synthesis 1994, 639 -
10a
Roush WR.Walts AE.Hoong LK. J. Am. Chem. Soc. 1985, 107: 8186 -
10b
Roush WR. Methods of Organic Chemistry (Houben-Weyl), In Stereoselective Synthesis E 21ed. Vol 3:Helmchen G.Hoffmann RW.Mulzer J.Schaumann E. ThiemeVerlag; Stuttgart: 1996. p.1410 - 11
Hughes DL. Org.Prep. Proced. Int. 1996, 28: 127 -
12a
Dess DB.Martin JC. J.Am. Chem. Soc. 1991, 113: 7277 -
12b
Boeckmann RK.Shao P.Mullins JJ. Org. Synth. 1999, 77: 141 - 13
Corey EJ.Helal CJ. Angew. Chem. Int. Ed. 1998, 37: 1986 ; Angew. Chem. 1998, 110, 2092 - 14
Fürstner A.Langemann K. J. Am. Chem. Soc. 1997, 119: 9130 -
15a
Grubbs RH.Chang S. Tetrahedron 1998, 54: 4413 -
15b
Fürstner A. Angew. Chem. Int. Ed. 2000, 39: 3012 ; Angew. Chem. 2000, 112, 3141 - 16
Kobayashi K.Lambert JB. J. Org. Chem. 1977, 42: 1254 - 18
Mosettig E.Mozingo R. Org. React. 1948, 4: 362 -
19a
Rodríguez A.Nomen M.Spur BW.Godfroid JJ. Tetrahedron Lett. 1999, 40: 5161 -
19b
Rodríguez A.Nomen M.Spur BW.Godfroid JJ.Lee TH. Tetrahedron 2001, 57: 25 ; and references cited therein -
20a
Takai K.Nitta K.Utimoto K. J. Am. Chem. Soc. 1986, 108: 7408 -
20b
Evans DA.Black WC. J.Am. Chem. Soc. 1993, 115: 4497 -
20c
Fürstner A. Chem. Rev. 1999, 99: 991 ; and references cited therein -
21a
Kobayashi Y.Shimazaki T.Taguchi H.Sato F. J. Org.Chem. 1990, 55: 5324 -
21b
Treilhou M.Fauve A.Pougny J.-R.Prome J.-C.Veschambre H. J.Org. Chem. 1992, 57: 3203
References
Spectroscopic data of the key intermediate 15: [α]D 20 = 57(c 0.96, CHCl3). IR(film): ν = 2957(br OH), 2861, 2622, 1729 (C=O), 1718 (C=O) cm-1.HRMS (CI, 70 eV) for [M + H+] (C9H13O4):Calcd 185.0755. Found: 185.0808. 1H NMR (500MHz, CDCl3): δ = 1.09 (ddd, 3 J = 8.5 Hz, 3 J = 6.8 Hz, 2 J 4a,4b = 4.7Hz, 1 H, 4-Ha), 1.29 (ddd, 3 J = 9.4 Hz, 3 J = 4.7 Hz, 2 J 4b,4a = 4.6Hz, 1 H, 4-Hb), 1.72 (1 H, dddd, 2 J 5 ′ a,5 ′ b = 13.8 Hz, 3 J 5 ′ a,4 ′ a = 11.7Hz, 3 J 5 ′ a,6 ′ = 10.6 Hz, 3 J 5 ′ a,4 ′ b = 5.0Hz, 5′-Ha), 1.75-1.79 (2 H, m c , 2-H, 3-H), 1.84 (ddddd, 2 J 4 ′ a,4 ′ b = 13.0 Hz, 3 J 4 ′ a,5 ′ a ′ = 11.7 Hz, 3 J 4 ′ a,3 ′ a = 9.0 Hz, 3 J 4 ′ a,3 ′ b = 7.0Hz, 3 J 4 ′ a,5 ′ b = 4.7Hz, 1 H, 4′-Ha), 1.97 (ddddd, 2 J 4 ′ b,4 ′ a = 13.0 Hz, 3 J 4 ′ b,3a ′ = 7.1Hz, 3 J 4 ′ b,3 ′ b = 5.0Hz, 3 J 4 ′ b,5 ′ a = 5.0Hz, 3 J 4 ′ b,5 ′ b = 4.7Hz, 1 H, 4′-Hb), 2.05 (1 H, ddddd, 2 J 5 ′ b,5 ′ a = 13.8Hz, 3 J 5 ′ b,4 ′ b = 4.7Hz, 3 J 5 ′ b,4 ′ a = 4.7Hz, 3 J 5 ′ b,6 ′ = 3.3Hz, 4 J 5 ′ b,3 ′ b = 1.3Hz, 5′-Hb), 2.48 (ddd, 2 J 3 ′ a,3 ′ b = 17.9 Hz, 3 J 3 ′ a,4 ′ a = 9.0Hz, 3 J 3 ′ a,4 ′ b = 7.1Hz, 3′-Ha), 2.59 (dddd, 2 J 3 ′ b,3 ′ a = 17.9 Hz, 3 J 3 ′ b,4a ′ = 7.0 Hz, 3 J 3 ′ b,4b ′ = 5.0 Hz, 4 J 3 ′ b,5 ′ b = 1.3Hz, 1-H, 3′-Hb), 3.91 (1 H, ddd, 3 J 6 ′ ,5 ′ b = 10.6 Hz, 3 J 6 ′ ,3 = 6.7Hz, 3 J 6 ′ ,5 ′ b = 3.3Hz, 6′-H), 10.74 (1 H, b, COOH). 13CNMR (125 MHz, CDCl3): δ = 12.1 (C-4),17.8 (C-3), 18.3 (C-4′), 26.6 (C-2), 27.8 (C-5′),29.4 (C-3′), 80.9 (C-6′), 171.4 (C-2′),179.0 (COOH).