Subscribe to RSS
DOI: 10.1055/s-2007-991054
Total Synthesis of (+)-Camptothecin via an Intramolecular Palladium-Catalyzed Cyclization Strategy
Publication History
Publication Date:
25 September 2007 (online)
Abstract
The novel cascade intramolecular Pd-catalyzed cyclization followed by aromatization for the construction of d ring of (+)-camptothecin as a key step is demonstrated.
Key words
natural products - alkaloids - antitumor - palladium - cyclizations
- 1
Wall ME.Wani MC.Cook CE.Palmer KH.McPhail AT.Sim GA. J. Am. Chem. Soc. 1966, 88: 3888 - 2
Hecht SM.Newman DJ.Kingston DGI. J. Nat. Prod. 2000, 63: 1273 - 3
Kitajima M.Yoshida S.Yamagata K.Nakamura M.Takayama H.Saito K.Seki H.Aimi N. Tetrahedron 2002, 58: 9169 - 4
Wu TS.Chan Y.Leu YL.Chen CY.Chen CF. Phytochemistry 1996, 42: 907 - 5
Govindachari TR.Viswanathan N. J. Chem. Soc., Perkin Trans. 1 1974, 1215 - 6
Priel E.Showalter SD.Blair DG. AIDS Res. Hum. Retroviruses 1991, 7: 65 -
7a
Stork G.Schultz AG. J. Am. Chem. Soc. 1971, 93: 4074 -
7b
Corey EJ.Crouse DN.Anderson JE. J. Org. Chem. 1975, 40: 2140 -
7c
Volkmann R.Danishefsky S.Eggler J.Solomon DM. J. Am. Chem. Soc. 1971, 93: 5576 -
7d
Tang CFS.Morrow CJ.Rapoport H. J. Am. Chem. Soc. 1975, 97: 159 -
7e
Du W. Tetrahedron 2003, 59: 8649 -
7f
Twin H.Batey RA. Org. Lett. 2004, 6: 4913 -
7g
Elban MA.Sun W.Eisenhauer BM.Gao R.Hecht SM. Org. Lett. 2006, 8: 3513 -
7h
Zhou HB.Liu GS.Yao ZJ. Org. Lett. 2007, 9: 2003 -
8a
Chavan SP.Venkatraman MS. Tetrahedron Lett. 1998, 39: 6745 -
8b
Chavan SP.Sivappa R. Tetrahedron Lett. 2004, 45: 3113 -
8c
Chavan SP.Pasupathy K.Venkatraman MS.Kale RR. Tetrahedron Lett. 2004, 45: 6879 -
8d
Chavan SP.Sivappa R. Tetrahedron Lett. 2004, 45: 3941 -
8e
Chavan SP.Venkatraman MS. ARKIVOC 2005, (iii): 165 - 9
Clement WH.Selwitz CM. J. Org. Chem. 1964, 29: 241 - 10
Aggarwal VK.Astle CJ.Rogers-Evans M. Org. Lett. 2004, 6: 1469 - 11
Georgiev VS.Smithers DA.Shamma M. Tetrahedron 1973, 29: 1949 - 12
Hayashi T.Hegedus LS. J. Am. Chem. Soc. 1977, 99: 7093 - 13
Liu C.Wang X.Pei T.Widenhoefer RA. Chem. Eur. J. 2004, 10: 6343 - 15
Earl RA.Vollhardt KPC. J. Org. Chem. 1984, 49: 4786 - 16
Quick J. Tetrahedron Lett. 1977, 327 -
17a
Curran DP.Ko S.-B.Josien H. Angew. Chem., Int. Ed. Engl 1995, 34: 2683 -
17b
Curran DP.Liu H.Josien H.Ko S.-B. Tetrahedron 1996, 52: 11385 -
17c
Josien H.Ko S.-B.Bom D.Curran DP. Chem. Eur. J. 1998, 4: 67 -
17d
Fang FG.Xie S.Lowery MW. J. Org. Chem. 1994, 59: 6142 -
17e
Jew S.-s.Ok K.-d.Kim H.-j.Kim MG.Kim JM.Hah JM.Cho Y.-s. Tetrahedron: Asymmetry 1995, 6: 1245 - 18
Zhou HB.Liu GS.Yao ZJ. Org. Lett. 2007, 9: 2003
References and Notes
Synthesis of Compound 23: Procedure for the Pd-Catalyzed Cyclization Reaction
To a stirred solution of compound 22 (0.2 g, 0.61 mmol) in DMF (3.0 mL) and H2O (1.0 mL) was added PdCl2 (0.007 g, 0.061 mmol) and CuCl2·2H2O (0.22 g, 1.2 mmol). The resultant dark green solution was heated at 95 °C for 8 h. After the disappearance of starting material (TLC), the reaction mixture was cooled to r.t. Then, H2O (10 mL) was added and extracted with Et2O (3 × 15 mL). The combined organic layers were washed with H2O (3 × 10 mL), brine (10 mL), dried over anhyd Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatog-raphy (SiO2) using EtOAc-PE (6:4) as an eluent to furnish cyclized product 23 as a pale yellow solid in 54% yield, mp 97-100 °C.
Spectroscopic Data for Compound 23
IR (CHCl3): νmax = 1728, 1658, 1604 cm-1. 1H NMR (400 MHz, CDCl3 and CCl4): δ = 1.44 (3 H, t, J = 7.2 Hz), 2.46 (3 H, s), 4.46 (2 H, q, J = 7.2 Hz), 5.27 (2 H, s), 7.21 (1 H, s), 7.66 (1 H, t, J = 8.0 Hz), 7.82 (1 H, t, J = 8.0 Hz), 7.92 (1 H, d, J = 8.0 Hz), 8.22 (1 H, d, J = 8.0 Hz), 8.37 (1 H, s) ppm. 13C NMR (100 MHz, CDCl3 and CCl4): δ = 14.3, 20.4, 50.15, 61.5, 103.5, 124.0, 127.95, 128.1, 129.1, 129.8, 130.5, 131.0, 136.0, 145.7, 148.9, 151.0, 152.4, 158.4, 166.3 ppm. ESI-MS: m/z = 321 [M + H]+, 343 [M + Na]+. Anal. Calcd (%) for C19H16N2O3: C, 71.24; H, 5.03; N, 8.74. Found: C, 71.19; H, 5.11; N, 8.69.