Palladium-catalyzed direct mono-aroylation of O-arylmethyl and aryl-substituted acetoxime ethers.

An efficient palladium-catalyzed ortho-aroylation of O-arylmethyl and aryl-substituted acetoxime ethers has been developed; this method has high mono-site selectivity and does not require exogenous ligands. Under the direction of a simple exo-acetoxime auxiliary, a broad scope of masked arylmethyl alcohols and phenols as well as various aromatic aldehydes are compatible with this transformation, which probably follows a mechanistic pathway involving a six- or five-membered exo-cyclopalladated intermediate. The strategy can be expediently adopted to prepare synthetically valuable 1H-benzo[d][1,2]oxazines and benzo[d]isoxazoles.

Synthesis and antitumor activity of novel substituted uracil-1'(N)-acetic acid ester derivatives of 20(S)-camptothecins.

A series of novel substituted uracil-1'(N)-acetic acid esters (6-20) of camptothecins (CPTs) were synthesized by the acylation method. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most of the derivatives exhibited comparable or superior cytotoxicity compare to CPT (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy.

Synthesis and cytotoxicity of novel 20-O-linked homocamptothecin ester derivatives as potent topoisomerase I inhibitors.

In an attempt to improve the antitumor activity of homocamptothecins (hCPTs), a series of novel 20-O-linked hCPT ester derivatives were first designed and synthesized based on a synthetic route, by which hCPTs are acylated with different substituted phenoxyacetic acid ester derivatives. Most of the derivatives were assayed for in vitro cytotoxicity against six human cancer cell lines KB, KB/VCR, A549, HCT-8, Bel7402, and A2780, and most of the assayed compounds exhibited good antiproliferative activity on these tumor cell lines especially on KB.

Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.

Aim: To improve the biological activity of A-ring modified analogues of camptothecin.

Methods: A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested.

Synthesis and antitumor activity of 20-O-linked nitrogen-based camptothecin ester derivatives.

A series of nitrogen-based 20S-hydroxyl camptothecin ester derivatives were prepared. 3-Aminopropionate of camptothecin was found more cytotoxic in vitro on several human tumor cell lines than 3-amidopropionate of camptothecin. Ester 16 showed best antitumor activity in vivo and in vitro in all esters we prepared.