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DOI: 10.1055/s-2005-863739
Synthesis of the AC Ring of Paclitaxel: Formation of the C Ring by [3+2] Cycloaddition with a Preformed A Ring
Publication History
Publication Date:
09 March 2005 (online)
Abstract
The stereoselective formation of the C ring was accomplished by nitrile oxide [3+2] cycloaddition of an intermediate with the A ring already constructed. We found that stereoelectronic effect to a 1,1-substituted alkene moiety is important in the reaction.
Key words
paclitaxel - nitrile oxide - cycloadditions
- For a recent review, see:
-
1a
Kingston DGI. Chem. Commun. 2001, 867 -
1b
Kingston DGI.Jagtap PG.Yuan H.Samala L. In Progress in the Chemistry of Organic Natural Products Vol. 84:Herz W.Falk H.Kirby GW. Springer; Wien, New York: 2002. p.53 -
2a
Takahashi T.Iwamoto H.Nagashima K.Okabe T.Doi T. Angew. Chem., Int. Ed. Engl. 1997, 36: 1319 -
2b
Miyamoto S.Doi T.Takahashi T. Synlett 2002, 97 -
3a
Takahashi T.Iwamoto H. Tetrahedron Lett. 1997, 38: 2483 -
3b
Takahashi T.Hirose Y.Iwamoto H.Doi T. J. Org. Chem. 1998, 63: 5742 -
4a
Nakai K.Kamoshita M.Doi T.Yamada H.Takahashi T. Tetrahedron Lett. 2001, 42: 7855 -
4b
Nakai K.Miyamoto S.Sasuga D.Doi T.Takahashi T. Tetrahedron Lett. 2001, 42: 7859 -
4c
Fuse S.Hanochi M.Doi T.Takahashi T. Tetrahedron Lett. 2004, 45: 1961 -
5a
Alcaraz L.Harnett JJ.Mioskowski C.Le Gall T.Shin D.-S.Falck JR. J. Org. Chem. 1995, 60: 7209 -
5b
Nivlet A.Dechoux L.Martel J.-P.Proess G.Manner D.Alcaraz L.Harnett JJ.Le Gall T.Mioskowski C. Eur. J. Org. Chem. 1999, 3241 -
6a
Brown FK.Raimondi L.Wu Y.-D.Houk KN. Tetrahedron Lett. 1992, 33: 4405 -
6b
Raimondi L.Wu Y.-D.Brown FK.Houk KN. Tetrahedron Lett. 1992, 33: 4409 - 7
Takahashi T.Nakazawa M.Sakamoto Y.Houk KN. Tetrahedron Lett. 1993, 34: 4075 - 8
Lee GA. Synthesis 1982, 508 - 9
Majumdar S.Bhattacharjya A.Patra A. Tetrahedron Lett. 1997, 38: 8581 -
12a
Nicolaou KC.Yang Z.Sorensen EJ.Nakada M. J. Chem. Soc., Chem. Commun. 1993, 1024 -
12b
Di Grandi MJ.Jung DK.Krol WJ.Danishefsky SJ. J. Org. Chem. 1993, 58: 4989
References
The structure of 7 was determined based on 1H NMR and DEPT spectra.
11The β-elimination of the 5-acetoxy group in 13 disabled further transformation.
13The aldehyde 15 was prepared as follows: (i) LDA, ethyl 3-methyl-2-butenoate; 2,4-O-benzylidene-2,4-dihydroxy-butanal, 50% d.s., cf. ref.3b; (ii) LiAlH4; (iii) TBSCl; (iv) SEMCl; (v) TBAF; (vi) TPAP, NMO.
14The stereochemistry was determined by the 1H NMR coupling constants (J 2,3 = J 3,4 = 10 Hz) after acetonide formation for 2,4-diol from 17.
15Spectral data of 22: IR (neat): 2957, 1798, 1726, 1463, 1362, 1250, 1150, 1070, 837 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.02 (s, 9 H), 0.12 (s, 3 H), 0.15 (s, 3 H), 0.89 (s, 9 H), 0.86-0.97 (m, 2 H), 1.03 (s, 3 H), 1.11 (s, 3 H), 1.20 (s, 9 H), 1.33 (s, 3 H), 1.72 (s, 3 H), 2.00-2.17 (m, 2 H), 2.31-2.52 (m, 2 H), 2.43 (dd, 1 H, J = 1.93, 15.00 Hz), 2.69 (dd, 1 H, J = 2.90, 15.00 Hz), 2.87 (d, 1 H, J = 10.60 Hz), 3.55 (dt, 1 H, J = 6.28, 10.10 Hz), 3.60 (d, 1 H, J = 7.25 Hz), 3.74 (dt, 1 H, J = 6.28, 10.10 Hz), 3.77 (d, 1 H, J = 10.60 Hz), 4.15 (d, 1 H, J = 7.25 Hz), 4.32 (s, 1 H), 4.53-4.60 (m, 1 H), 4.56 (d, 1 H, J = 12.60 Hz), 4.60 (d, 1 H, J = 12.60 Hz), 4.70 (d, 1 H, J = 6.77 Hz), 4.81 (d, 1 H, J = 6.77 Hz). 13C NMR (99.6 MHz, CDCl3): δ = -4.5 (CH3), -4.3 (CH3), -1.3 (CH3), 17.7 (CH3), 18.2 (C), 18.3 (CH2), 19.5 (CH3), 24.0 (CH2), 25.8 (CH3), 25.9 (CH3), 27.27 (CH3), 27.35 (CH3), 29.4 (CH2), 29.6 (CH2), 38.9 (C), 43.0 (C), 43.7 (CH), 56.0 (C), 61.1 (CH2), 66.7 (CH2), 68.6 (CH), 78.0 (CH), 80.9 (CH2), 81.4 (CH), 88.7 (C), 96.5 (CH2), 126.4 (C), 136.5 (C), 154.8 (C), 160.0 (C), 178.6 (C). ESI-TOF: m/z = 724.4 [M + H]+.