Abstract
The synthesis of optically active [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), a key intermediate for the total asymmetric synthesis of 20(S)-camptothecin anticancer drugs, is described. Its structure was characterized by 2D-NMR techniques and the absolute configuration was further confirmed for the first time by X-ray crystal structure analysis.
Highlights
20(S)-Camptothecins [20(S)-CPTs] (Figure 1) have attracted lasting interest in organic synthetic chemistry due to their unique chemical structures and potent antitumor activities, and considerable effort has been devoted over the last thirty years to the development of elegant methods for the total synthesis of 20(S)-CPTs [1]
We were especially interested in the asymmetric synthesis of compound 2 developed by Tagawa et al [2] for its use of commercially available starting materials, mild reaction conditions and simple manipulations
As a part of our continuing program [5] to explore a practical and commercial route of 20(S)-CPTs, we report the preparation and structural analysis of [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), which is the key intermediate in the synthesis of lactone 2
Summary
20(S)-Camptothecins [20(S)-CPTs] (Figure 1) have attracted lasting interest in organic synthetic chemistry due to their unique chemical structures and potent antitumor activities, and considerable effort has been devoted over the last thirty years to the development of elegant methods for the total synthesis of 20(S)-CPTs [1]. Molecules 2007, 12 synthetic methods for the preparation of compound 2 have been reported using a chiral auxiliary to induce asymmetry [2], a chemocatalyst to catalyze asymmetric synthesis [3] and optical resolution [4]. As a part of our continuing program [5] to explore a practical and commercial route of 20(S)-CPTs, we report the preparation and structural analysis of [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), which is the key intermediate in the synthesis of lactone 2.
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