Synthetic method of 8-epi-puupehedione

Abstract

The invention relates to a synthetic method of a sea natural product 8-epi-puupehedione, which belongs to the field of chemical synthesis. According to the invention, salvia sclarea aldehyde and 1-iodine-2,4,5-trialkoxy benzene are used as starting materials, salvia sclarea aldehyde and p-toluenesulfonhydrazide generate salvia sclarea hydrazone 2, the salvia sclarea hydrazone 2 and 1-iodine-2,4,5-trialkoxy benzene form a framework compound 4 of puupehedione under the catalysis of palladium in a coupling manner, the framework compound 4 is subjected to one-step hydroxyl reduction and double-bond isomerization under the action of a reducing agent to obtain an intermediate 5, the intermediate 5 is oxidized into an intermediate quinone compound 6 under the action of an oxidizing agent, and isomerization and Diels-Alder ring closure are realized for the quinone compound 6 under alkaline condition, then an intermediate 7 is obtained, and the intermediate 7 is further oxidized to obtain the final product 8-epi-puupehedione. The method has the characteristics of less reaction step, simple operation, and good products selectivity, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a synthesis method of marine natural product 8-epi-puupehedione. Background technique [0002] The compound 8-epi-puupehedione is the epimer with the opposite orientation of the methyl group at the 8-position of the marine natural product puupehedione, and it is a derivative of the active marine natural product puupehedione. In 2004, Quesada et al. reported that the compound 8-epi-puupehedione is a very active angiogenesis inhibitor. (M. E. Castro, M.González-Iriarte, A. F. Barrero, N. Salvador-Tormo, R. Muñoz-Chápuli , M. Á. Medina and A. R. Quesada, Int. J. Cancer, 2004, 110, 31.). [0003] There are few reports on the synthetic methods of 8-epi-puupehedione, and the yields are low. In 1999, Barrero et al. reported an acid-catalyzed ring-closing method for phenolic hydroxyl groups to attack alkenes, and obtained a mixture with different orientations of the 8-position methyl groups, resulting in low yields (A. F. Barrero, E....

AI Technical Summary

Problems solved by technology

In 1999, Barrero et al. reported an acid-catalyzed ring-closing method for phenolic hydroxyl groups to attack alkenes, and obtained a mixture with different orientations of the 8-position methyl groups, resulting in low yields (A. F. Barrero, E. J. Alvarez-Manzaneda, R. Chahboun , M. Cortés and V. Armstrong, Tetrahedron, 1999, 55, 15181.)

In 2003, Armstrong et al. used natural (-)-drimenol as a starting material and used a similar acid-catalyzed cyclization method to obtain a mixture with different methyl orientations. Not only the yield was low, but the starting material was expensive. greatly contributes to the production costs of this method (Armstrong, A. F.Barrero, E. J. Alvarez-Manzaneda, M. Corte´s, and B. Sepulveda, J. Nat.Prod., 2003, 66, 1382.)

Yamamoto et al. reported in 2004 that the compound 8-epi-puupehedione was synthesized by Brönsett acid-promoted polyene tandem cyclization method. It greatly increases the cost and is not conducive to industrial production (H. Ishibashi, K. Ishihara and H. Yamamoto, J. Am. Chem. Soc., 2004, 126, 11122.)

The above methods all have unfavorable factors such as high cost or extremely low yield, and are not suitable for industrial production.

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