Regio- and stereospecific synthesis of mono-beta-d-glucuronic acid derivatives of combretastatin A-1.
Synthetic routes have been established for the preparation of regio- and stereoisomerically pure samples of the mono-beta-d-glucuronic acid derivatives of combretastatin A-1, referred to as CA1G1 (5a) and CA1G2 (6a). Judicious choice of protecting groups for the catechol ring was required for the regiospecific introduction of the glucuronic acid moiety. The tosyl group proved advantageous in this regard. The two monoglucuronic acid analogues demonstrate low cytotoxicity (compared to CA1, 2) against selected human cancer cell lines, with CA1G1 being slightly more potent than CA1G2.
Tanpure
Rajendra P
RP
Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, USA.
Strecker
Tracy E
TE
Chaplin
David J
DJ
Siim
Bronwyn G
BG
Trawick
Mary Lynn
ML
Pinney
Kevin G
KG
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D020723:Glucuronic Acid / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C063690:combretastatin A-1; D020723:Glucuronic Acid