Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 14. Synthesis of (±)-Duocarmycin SA, Natural (+)-Duocarmycin SA and Non-natural (-)-Duocarmycin SA

スポンサーリンク

概要

• 論文の詳細を見る

• Total synthesis of duocarmycin SA (1), an extremely potent cytotoxic antibiotic, was achieved in the racemic form at first by effectively utilizing two reactions as key steps, (i) an intramolecular Heck reaction of the benzyl ether 21a, derived from a dihydropyridine 13a and a pyrrole derivative 11,to form tricyclic compounds 25a and 26a, and (ii) a modified Mitsunobu reaction on the diol derivative 40 for the construction of compound 41 having the pivotal pharmacophore of a cyclopropanoindolinone partial structure, which is critical for the high biological activities of 1. Next, optical resolution of an intermediary racemic secondary alcohol 50 was cleanly attained by derivatizing it to (R)-O-methylmandelates 52 and 53,and the resulting chiral alcohols (+)-50 and (-)-50 were respectively transformed into unnatural (-)-1 and natural (+)-1. Finally inversion of the secondary alcohol (+)-50 to the enantiomer (-)-50 was effected by using the Mitsunobu reaction. This constitutes an enantio-convergent total synthesis of natural duocarmycin SA (1) starting from a racemic compound.

• 公益社団法人日本薬学会の論文
• 1996-01-15

著者

• MURATAKE Hideaki

  Research Foundation Itsuu Laboratory

• NATSUME Mitsutaka

  Research Foundation Itsuu Laboratory

• Abe I

  Univ. Shizuoka Shizuoka Jpn

• ABE Itsuko

  Research Foundation Itsuu Laboratory

関連論文

• Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 15. Asymmetric Synthesis of (+)-Duocarmycin SA Using Novel Procedure for Preparation of Hydroxyindoles
• Synthesis of Duocarmycin SA by Way of Methyl 4-(Methoxycarbonyl)oxy-3H-pyrrolo[3,2-f]quinoline-2-carboxylate as a Tricyclic Heteroaromatic Intermediate
• Synthesis of Furan and Thiophene Analogs of Duocarmycin SA
• ALTERNATIVE SYNTHESIS OF DUOCARMYCIN SA USING A TRICYCLIC HETEROAROMATIC INTERMEDIATE PREPARED BY PALLADIUMCATALYZED COUPLING REACTIONS
• PB116 SYNTHETIC INVESTIGATION OF TOMOR PROMOTORS, TELEOCIDINS
• Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 14. Synthesis of (±)-Duocarmycin SA, Natural (+)-Duocarmycin SA and Non-natural (-)-Duocarmycin SA
• Preparation of Benzene, Furan, and Thiophene Analogs of Duocarmycin SA Employing a Newly-Devised Phenol-Forming Reaction
• Disposition of a New Tamibarotene Prodrug in Mice
• Novel Synthesis of Ureas: Application of t-Butylureas

スポンサーリンク