RSS-Feed abonnieren
DOI: 10.1055/s-2003-42467
Enantioselective Formal Synthesis of Eleuthesides
Publikationsverlauf
Publikationsdatum:
07. November 2003 (online)
![](https://www.thieme-connect.de/media/synlett/200315/lookinside/thumbnails/10.1055-s-2003-42467-1.jpg)
Abstract
An intramolecular Diels-Alder reaction of an enantiopure 3,5-hexadienyl acrylate and a chemoselective epimerization constitute the key steps of a highly stereoselective synthesis of triol 25, whose conversion to eleutherobin, eleuthosides A and B and sarcodictyins A and B is known.
Key words
antitumor agents - stereoselective addition reactions - organometallic reagents - intramolecular Diels-Alder reactions - chemoselective epimerization
- 1 For a review, see:
Nicolaou KC.Pfefferkorn J.Xu J.Winssinger N.Ohshima T.Kim S.Hosokawa S.Vourloumis D.van Delft F.Li T. Chem. Pharm. Bull. 1999, 47: 1199 -
2a
Nicolaou KC.Ohshima T.Hosokawa S.van Delft FL.Vourloumis D.Xu JY.Pfefferkorn J.Kim S. J. Am. Chem. Soc. 1998, 120: 8674 -
2b
Nicolaou KC.Xu JY.Kim S.Pfefferkorn J.Ohshima T.Vourloumis D.Hosokawa S. J. Am. Chem. Soc. 1998, 120: 8661 - 3
Chen X.-T.Bhattacharya SK.Zhou B.Gutteridge CE.Pettus TRR.Danishefsky SJ. J. Am. Chem. Soc. 1999, 121: 6563 - For recent synthetic studies toward eleuthesides, see:
-
4a
Winkler JD.Quinn KJ.MacKinnon CH.Hiscock SD.McLaughlin EC. Org. Lett. 2003, 5: 1805 -
4b
Kaliappan KP.Kumar N. Tetrahedron Lett. 2003, 44: 379 ; and references cited therein - 5
Plietker B. Ph.D. Thesis Technische Universität Dresden; Germany: 1999. -
6a
Ishikawa T.Senzaki M.Kadoya R.Morimoto T.Miyake N.Izawa M.Saito S. J. Am. Chem. Soc. 2001, 123: 4607 -
6b
Jung ME.Huang A.Johnson TW. Org. Lett. 2000, 2: 1835 -
6c
Kim P.Nantz MH.Kurth MJ.Olmstead MM. Org. Lett. 2000, 2: 1831 - 7
Wilson SR.Jernberg KM.Mao DT. J. Org. Chem. 1976, 41: 3209 -
8a
Lattanzi A.Sagulo F.Scettri A. Tetrahedron: Asymmetry 1999, 10: 2023 -
8b
Mulzer J.Berger M. Tetrahedron Lett. 1998, 39: 803 -
8c
Menzel A.Oehrlein R.Griesser H.Wehner V.Jäger V. Synthesis 1999, 1691 - 9
Mengel A.Reiser O. Chem. Rev. 1999, 99: 1191 -
12a
Wilson SR.Mao DT.Jernberg KM.Ezmirly ST. Tetrahedron Lett. 1977, 18: 2559 -
12b
Shing TKM.Zhu XY.Mak TCW. Chem. Commun. 1996, 2369 - 13
Han Y.Liao S.Qiu W.Cai C.Hruby VJ. Tetrahedron Lett. 1997, 38: 5135 -
15a
Jones GA.Paddon-Row MN.Sherburn MS.Turner CI. Org. Lett. 2002, 4: 3789 -
15b
Tantillo DJ.Houk KN.Jung ME. J. Org. Chem. 2001, 66: 1938 - 16
Saito A.Ito H.Taguchi T. Org. Lett. 2002, 4: 4619 - 18
Lee AS.-Y.Hu Y.-J.Chu S.-F. Tetrahedron 2001, 57: 2121 -
20a
Ihara M.Suzuki S.Taniguchi N.Fukumoto K. J. Chem. Soc., Perkin Trans. 1 1993, 2251 -
20b
Bartlett PA.Meadows JD.Ottow E. J. Am. Chem. Soc. 1984, 106: 5304
References
The relative configuration of 8 and 9 was elucidated by a NOESY experiment with acetonide A (Figure [2] ) prepared from 8/9 by desilylation (40% HF, MeCN, r.t., 90% from 8, 78% from 9) and subsequent acetalization of the resulting single diol (acetone, PPTS, r.t., 91%).
11Upon changing the lactaldehyde protecting group to TBDPS, [8b] silyl migration was slightly diminished, while complete Felkin-Anh selectivity of addition was maintained. However, the corresponding products were less readily separated. With MOM protection [8c] the diastereo-selectivity of addition was too low for synthetic utilization. Transmetalation from Li to Al (Me2AlCl) or Mg (MgBr2 etherate) gave less 8/9.
14The relative configuration was verified by detailed 2D NMR experiments.
17Attempted IMDA reactions of alcohol 17 and the corresponding ketone [DMSO, (COCl)2, Et3N, CH2Cl2, -50 °C to r.t., 84% from 17] under similar conditions turned out to be much less efficient (<25% yield).
19Alcohol 21 was also obtained by desilylation of 13 (40% HF, MeCN, r.t., 98%).
21Compound 25: [α]D 25 +41.6 (c 0.6, CHCl3); ref. [2b] [α]D 25 +43.5 (c 0.2, CHCl3).