Method for synthesizing 8th-site substituted-3,4,7,8-tetrahydro-2H-oxocin-2-one octatomic ring

Abstract

The invention discloses a method for synthesizing 8th-site substituted-3,4,7,8-tetrahydro-2H-oxocin-2-one octatomic ring. The synthesis method includes the following steps: performing Grignard reaction on an aldehyde or ketone to obtain an allyl alcohol compound; and performing condensation reaction with 2-(tert-butylsulfonyl)acetic acid to obtain an allyl (tert-butylsulfonyl)acetate compound; performing olefin cross-metathesis reaction under the action of a second generation Grubbs catalyst to obtain a methoxycarbonyl (tert-butylsulfonyl)acetate compound; performing intramolecular reaction byusing anhydrous N,N-dimethylformamide as a solvent in the presence of a catalyst palladium acetate and a ligand triphenylphosphine, so as to produce a 3-tert-butylsulfonyl 8th-site substituted-3,4,7,8-tetrahydro-2H-oxocin-2-one octatomic ring lactone compound; and finally removing tert-butylsulfonyl in a reaction solution of sodium amalgam and acetic acid by taking ethanol as a solvent, so as toobtain 8th-site substituted-3,4,7,8-tetrahydro-2H-oxocin-2-one octatomic ring lactone compound. The yield of the method is high, and a solution with a very dilute reaction concentration is not neededin the synthesis of various substituted octatomic ring lactones through intramolecular catalysis by palladium, so the process conditions are simple and universal.

Description

technical field [0001] The invention relates to a preparation method of an eight-membered ring skeleton compound, in particular to a synthesis method of an 8-substituted-3,4,7,8-tetrahydro-2H-oxooct-2-one eight-membered ring. Background technique [0002] Eight-membered ring skeleton compounds widely exist in marine microorganisms and plants, and most of the extracted eight-membered ring compounds have certain pharmacological activities. According to the research, the natural product with eight-membered ring skeleton extracted from marine Streptomyces marina has certain cytotoxicity to various cancer cells. In addition, eight-membered ring natural products extracted from marine actinomycetes from sea mangrove soils are biologically active against human DNA topoisomerase. With the extraction of various sesquiterpenoids, ophiobolin A, scientists discovered that the eight-membered ring natural product ophiobolin A has certain cytotoxicity to melanoma, glioma, and colorectal ca...

AI Technical Summary

Problems solved by technology

However, this reaction has a major defect in the synthesis of 8-membered ring compounds containing cis-type double bonds. In the absence of directing groups or the presence of rings, it is impossible to obtain a yield higher than 20%, which is mainly due to the eight-membered ring compound. Due to the high ring tension of the ring, there are also the following disadvantages: it is easy to produce a large number of 16-membered ring dimers or polymers; and it needs to be reacted at a high dilute concentration (10-3M-10-5M); And precious metals, such as ruthenium, rhodium, etc., are very difficult to completely remove from the product

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