- Asymmetric mannich-type addition of lithium glycolates to imines producing 3-hydroxy-4-phenylazetidin-2-ones
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The external chiral ligand-controlled asymmetric Mannich-type reaction of a binary-or ternary-complexed lithium ester enolate of protected glycolates with benzaldehyde imines gave the corresponding 3-trialkylsilyl-oxy-4-phenylazetidin-2-ones, applicable a
- Fujieda, Hiroki,Hata, Seiji,Yamada, Ken-ichi,Tomioka, Kiyoshi
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p. 603 - 610
(2007/10/03)
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- Structure-activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
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A series of new taxoids modified at the C-3′, C-3′N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mφ) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mφ-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mφ. Positions C-3′ and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3′N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN Mφ and the cytotoxicity against Mφ-like cells.
- Ojima, Iwao,Fumero-Oderda, Cecilia L.,Kuduk, Scott D.,Ma, Zhuping,Kirikae, Fumiko,Kirikae, Teruo
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p. 2867 - 2888
(2007/10/03)
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- New and efficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means of β-lactam synthon method
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Highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-β-lactams with excellent enantiomeric purity is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenyl-isoserine and its analogs. (3R,4S)-N-benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetidinone readily derived from the 3-hydroxy-4-phenyl-β-lactam is coupled with protected baccatin IIIs, followed by deprotection to give optically pure taxol and 10-deacetyl-7,10-bis(Troc)-taxol in good yields. Fully assigned 1H, 13C, and 2D (COSY and HETCOR) NMR spectra of taxol thus synthesized are shown and discussed.
- Ojima, Iwao,Habus, Ivan,Zhao, Mangzhu,Zucco, Martine,Park, Young Hoon,Sun, Chung Ming,Brigaud, Thierry
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p. 6985 - 7012
(2007/10/02)
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- Efficient and Practical Asymmetric Synthesis of the Taxol C-13 Side Chain, N-Benzoyl-(2R,3S)-3-phenylisoserine, and Its Analogues via Chiral 3-Hydroxy-4-aryl-β-lactams through Chiral Ester Enolate-Imine Cyclocondensation
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A highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-β-lactams with >96percent ee is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenylisoserine, and its analogues.
- Ojima, Iwao,Habus, Ivan,Zhao, Mangzhu,Georg, Gunda I.,Jayasinghe, Lalith R.
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p. 1681 - 1683
(2007/10/02)
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