Syntheses Of Analogues Of Howiinol A And Studies Of Their Relationship Of Structures And Antitumor Activities

Howiinol A ~1, a novel lactone isolated from the ethanolic extracts of the root and stem bark of Goniothamus howii Merr. (Annoaceae) in our laboratory, has been shown to possess significant antitumor activities toward human tumor in vitro and in vivo and low toxicity. In our previous work, we have synthesized Howiinol A and its derivatives with different ester groups. In order to find their relationship of structure and activity and to search for drugs with more potent antitumor activity, we have synthesized a series of compounds: Howiinol A and its analogues; analogues of (-)-8α-epi-howiinol A; 3,4-dihydro-howiinol A; p-methyl-ho-wiinol A and its analogues; 5,7-isopropylidene-m-methyl-goniotriol; p-chloro howiinol A and its analogues; 5,7-isopropylidene-o-methoxy-goniotriol, starting from commercially available α-D-glucoheptonic-γ-lactone. The route is depicted in the following scheme.