Thesis (Ph.D.)--Chulalongkorn University, 2005

The total synthesis of 6-deoxyclitoriacetal (39), a cytotoxic natural product, has been achieved by using PtCl[subscript2]-catalyzed hydroarylation, Sharpless asymmetric dihydroxylation, IBX regioselective diol oxidation and stereoselective intramolecular keto-aldehyde pinacol coupling as the key steps. The important steps of this synthesis began with the conversion of compund 1,2-dimethoxy-4-prop-2-ynyloxybenzene (75) into 6,7-dimethoxy-2H-chromene (83) using PtCl[subscript2]-catalyzed hydroarylation reaction successfully in good yield. The Sharpless asymmetric dihydroxylation of compound 83 provided a diol 84 which was converted into 3-hydroxy-6,7-dimethoxy-chroman-4-one (82) by selective oxidation with IBX in EtOAc. Conversion of [alpha]-hydroxy ketone 82 to a good leaving group, Tf (86), leaded to connection of D ring and A-B ring which was convinced by S[subscript N]2 reaction in very good yield (80%). The C ring was formed by SmI[subscript2]-promoted intramolecular Pinacol-type cyclization of 2-(6,7-dimethoxy-4-oxo-chroman-3-yloxy)-6-hydroxy-4-methoxybenzaldehyle (87) which was delivered the right stereogenic center at C 12a. Finally, completed synthesis of 6-deoxyclitoriacetal (39) was achieved by oxidation of 2,3,9-trimethoxy-6,6a-dihydro-12H-chromeno[3,4-b]chromene-11,12,12a-triol (88) with MnO[subscript2]. The compound 39 exhibited cytotoxic activity against human breast carcinoma (BT474), lung carcinoma (CHAGO), hepato carcinoma (HEP-G2), gastric carcinoma (KATO3) and colon carcinoma (SW620) at IC50 0.2, 0.9, 0.1, 0.3 and 0.1 [microgram]/mL, respectively.