Search

A six-step asymmetric total synthesis of (20S)-camptothecin (1) has been accomplished in 25% overall yield starting from the known pyridone 3. The key steps in this synthesis are the chemoselective Ni-catalyzed hydrogenation of 3-cyanopyridone 6 to 3-formylpyridone 7 in AcOH/pyridine/H2O and the Davis asymmetric hydroxylation of tricyclic lactone 4 utilizing a chiral N-sulfonyloxaziridine into (4′S)-tricyclic hydroxylactone 2.

An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine-catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.

A novel and convenient method for the stereoselective synthesis of d-biotin 1 starting from the commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 has been developed. The key features of this synthesis include the enantioselective reduction of a meso-cyclic imide, mediated by a chiral oxazborolidine catalyst, derived from (1S,2S)-(+)-threo-1-(4-nitrophenyl)-2-amino-1,3-propanediol and the direct introduction of a C5 side chain to the (3aS,6aR)-thiolactone through a modified di-Grignard reaction. Enantioselectivities of 98% in the oxazborolidine-catalyzed asymmetric reduction process have been achieved.

An efficient and highly enantioselective synthesis of d-biotin from the known cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (5) was accomplished in 48% overall yield. The key reactions in the sequence involve thecatalytic enantioselective reduction of meso-cyclic imide 6 using polymer-supported chiral oxazoborolidine, derived from (S)-α,α-diphenylprolinol and polymer-bound sulfonyl chloride, and the installation of the C 5 side chain at C4 in the thiolactone 9 via a Ni/C-catalyzed Fukuyama coupling reaction.

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. Keywords: Ethyl [ N -tosyl-( R )-prolyloxy]-2( S )-[4-cyano-8, 8-ethylenedioxy-5-oxo-5, 6, 7, 8-tetrahydroindolizin-3-yl] acetate; 2D-NMR techniques; X-ray crystal structure; configurational analysis. Introduction 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]. Among the numerous asymmetric synthesis approaches to these alkaloids described, the strategy utilizing the (

An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine-catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.