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Synthesis of novel 3′‐trifluoromethyl taxoids through effective kinetic resolution of racemic 4‐CF 3 ‐β‐lactams with baccatins
Author(s) -
Ojima Iwao,
Slater John C.
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:5/6<487::aid-chir15>3.0.co;2-k
Subject(s) - chemistry , enantiopure drug , enantiomer , kinetic resolution , chirality (physics) , enantioselective synthesis , stereochemistry , trifluoromethyl , imine , lactam , combinatorial chemistry , organic chemistry , catalysis , alkyl , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
The coupling of racemic 1‐ t Boc‐4‐CF 3 ‐β‐lactams with various C‐10 modified baccatins has resulted in CF 3 ‐taxoids with diastereoselectivities ranging from 9:1 to one single isomer. The observed high diastereoselectivity is ascribed to the highly efficient enantiomer‐differentiation by the enantiopure lithium alkoxide of a baccatin III in the coupling reaction with a racemic 1‐ t Boc‐β‐lactam. These novel CF 3 ‐taxoids have also been shown to exhibit significant increases in activity against various cancer cell lines compared to either paclitaxel or docetaxel. In addition, the first asymmetric synthesis of a CF 3 ‐β‐lactam via chiral ester enolate‐imine cyclocondensation was performed with 50% enantioselectivity. Chirality 9:487–494, 1997. © 1997 Wiley‐Liss, Inc.