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DOI: 10.1055/s-0031-1290357
Studies Toward Elucidating the Stereochemical Structure of Iriomoteolide 1a
Publication History
Publication Date:
24 February 2012 (online)
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Abstract
A diastereomer of iriomoteolide 1a has been synthesized as part of our effort to identify the so far unknown stereochemical structure of the natural product. The synthetic route features a lithium acetylide-chloroformate coupling, the ring-closing metathesis to form the macrocyclic diolide, and a SmI2-mediated intramolecular reductive allylation for formation of the cyclic hemiketal.
Key words
iriomoteolide - natural products - total synthesis - antitumor agent - reductive allylation - misassignment
- Supporting Information for this article is available online:
- Supporting Information
-
1a
Tsuda M.Oguchi K.Iwamoto R.Okamoto Y.Kobayashi J.Fukushi E.Kawabata J.Ozawa T.Masuda A.Kitaya Y.Omasa K. J. Org. Chem. 2007, 72: 4469 -
1b
Tsuda M.Oguchi K.Iwamoto R.Okamoto Y.Fukushi E.Kawabata J.Ozawa T.Masuda A. J. Nat. Prod. 2007, 70: 1661 -
2a
Liu Y.Wang J.Li H.Wu J.Feng G.Dai W.-M. Synlett 2010, 2184 -
2b
Paterson I.Rubenbauer P. Synlett 2010, 571 -
2c
Li S.Chen Z.Xu Z.Ye T. Chem. Commun. 2010, 46: 4773 -
2d
Xie J.Ma Y.Horne DA. Org. Lett. 2009, 11: 5082 -
2e
Wang S.-Y.Chen Y.-J.Loh T.-P. Synthesis 2009, 3557 -
2f
Ye Z.Deng L.Qian S.Zhao G. Synlett 2009, 2469 -
2g
Chin Y.-J.Wang S.-Y.Loh T.-P. Org. Lett. 2009, 11: 3674 -
2h
Xie J.Horne DA. Tetrahedron Lett. 2009, 50: 4485 -
2i
Ghosh AK.Yuan H. Tetrahedron Lett. 2009, 50: 1416 -
2j
Fang L.Xue H.Yang J. Org. Lett. 2008, 10: 4645 -
3a
Xie J.Ma Y.Horne DA. Tetrahedron 2011, 67: 7485 -
3b
Ghosh AL.Yuan H. Org. Lett. 2010, 12: 3120 -
3c
Xie J.Ma Y.Horne DA. Chem. Commun. 2010, 46: 4770 - For a recent synthesis of the proposed iriomoteolide 1b:
-
3d
Ye Z.Gao T.Zhao G. Tetrahedron 2011, 67: 5979 - 4
Fang L.Yang J.Yang F. Org. Lett. 2010, 12: 3124 -
5a
Liu Y.Feng G.Wang J.Wu J.Dai W.-M. Synlett 2011, 1774 -
5b
The spectra reported by Dai and co-workers for macrolide 2 are different from ours. In particular, a chemical shift of δ = 96.8 ppm was observed for 2 at C13 (and δ = 97.0 ppm for 6) in our hands, but δ = 99.5 ppm by Dai and co-workers and δ = 99.7 ppm for the natural product. It is not clear what is the source of this discrepancy.
- 8
Zhang D.Bleasdale C.Golding BT.Watson WP. Chem. Commun. 2000, 1141 - 9
Marshall JA. J. Org. Chem. 2007, 72: 8153 - 10
Evans DA.Bartroli J.Shih TL. J. Am. Chem. Soc. 1981, 103: 2127 -
11a
Levin JI.Turos E.Weinreb SM. Synth. Commun. 1982, 12: 989 -
11b
Basha A.Lipton M.Weinreb SM. Tetrahedron Lett. 1977, 18: 4171 -
12a
Miwa K.Aoyama T.Shioiri T. Synlett 1994, 107 - For a recent review, see:
-
12b
Habrant D.Rauhala V.Koskinen AMP. Chem. Soc. Rev. 2010, 39: 2007 - For two reviews of the Mitsunobu reaction, see:
-
13a
Mitsunobu O. Synthesis 1981, 1 -
13b
Kumara Swamy KC.Bhuvan Kumar NN.Balaraman E.Pavan Kumar KVP. Chem. Rev. 2009, 109: 2551 - 14
Scholl M.Ding S.Lee CW.Grubbs RH. Org. Lett. 1999, 1: 953 - 15
Finkelstein H. Ber. Dtsch. Chem. Ges. 1910, 43: 1528 - 16
Heumann LV.Keck GE. Org. Lett. 2007, 9: 1951 -
17a
Gaffney BL.Jones RA. Tetrahedron Lett. 1982, 23: 2257 -
17b
Coleman RS.Li J.Navarro A. Angew. Chem. Int. Ed. 2001, 40: 1736
References
Supporting Information of ref. 1.
7Fang, L.; Yang, J. unpublished results.
18
Characterization
Data for Compound 6
[α]D -11.07
(c 0.6, CHCl3). IR (thin film):
2967, 2928, 2854, 1661 1638, 1427, 1013, 871 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 5.72 (s,
1 H), 5.72-5.70 (m, 2 H), 5.62-5.57 (m, 1 H),
5.45 (dd, J = 16.2,
9.1 Hz, 1 H), 4.87 (s, 1 H), 4.85-4.80 (m, 1 H), 4.83 (s,
1 H), 3.77 (t, J = 9.1
Hz, 1 H), 3.64 (dd, J = 11.9,
2.4 Hz, 1 H), 3.61-3.53 (m, 1 H), 3.03 (s, 1 H), 2.50-2.46
(m, 1 H), 2.44-2.35 (m, 1 H), 2.33 (d, J = 8.1
Hz, 1 H), 2.25 (dd, J = 13.6,
10.3 Hz, 1 H), 2.17-2.11 (m, 3 H), 2.08 (s, 3 H), 2.06-1.98
(m, 1 H), 1.93-1.88 (m, 1 H), 1.84-1.79 (m, 1
H), 1.51-1.45 (m, 1 H), 1.28 (d, J = 6.8
Hz, 3 H), 1.15 (s, 3 H), 1.17-1.11 (m, 1 H), 1.07 (d, J = 6.3 Hz,
3 H), 1.02 (d, J = 7.1
Hz, 3 H), 0.85 (d, J = 6.8
Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 168.1,
162.6, 141.2, 139.0, 135.0, 128.0, 120.7, 115.7, 111.3, 97.0, 79.9,
75.8, 75.7, 73.7, 72.4, 48.4, 45.9, 43.8, 38.0, 37.0, 36.2, 35.4,
33.6, 23.2, 21.5, 20.4, 17.7, 16.9, 15.9. ESI-HRMS: m/z calcd for C29H46O7Na+
[M + Na+]:
529.3141; found: 529.3152.