Synthesis method of natural product (-)-newbouldine

Abstract

The invention discloses a synthesis method of a natural product (-)-newbolline. With optically-active Boc protected pyrrolidine formamide as a raw material, five chemical conversion processes are successively carried out, namely, a Grignard reaction, a Wittig reaction, a hydroboration-oxidation reaction, a hydroxyl azide reaction and an iron-catalyzed N-N cyclization reaction, so as to realize high-efficiency simple total synthesis of the natural product (-)-newbolline. The synthesis method has the advantages of simple operation, mild reaction conditions, easy post-treatment and high yield ofthe target compound. Compared with a reported synthetic route, the method disclosed by the invention does not need to use highly toxic cuprous cyanide, a large amount of titanium trichloride and a large amount of strong corrosive concentrated hydrochloric acid, and the dosage of the key N-N forming reaction catalyst in the last step only needs 0.02-0.05 chemical equivalent. Therefore, the invention provides an important method for large-scale preparation of the natural product (-)-newbolone.

Description

technical field [0001] The invention belongs to the technical field of synthesis of natural products, in particular to a synthesis method of natural product (-)-newbouldine. Background technique [0002] Natural products containing N-N bonds are rare in nature. The alkaloid newbouldine containing a hydrazone functional group in the molecule was first isolated in 1993 from the Bignoniaceae plant Newbouldia laevis in Ivory Coast, West Africa and other places (Burkill, H.M. The useful Plants of West tropical Africa; Royal Botanic Gardens, Kew: London; Vol. 1.). The root bark of this plant is used locally as a traditional herbal remedy for a variety of ailments such as enlarged spleen, dysentery, helminthiasis, migraines, earaches, conjunctivitis and various other inflammatory conditions. In-depth studies have found that newbouldine has neurophysiological activity (Saburi, A.A.; Nia, R.; Fontaine, C.; Pays, M. Phytochemistry. 1993, 35, 1053-1055.). Newbouldine has two chiral ...

AI Technical Summary

Problems solved by technology

Its synthetic route is shown below, in which, the phenyl copper lithium reagent needs to use the newly prepared CuCN 2LiCl as the catalyst, and the catalyst needs to pass LiCl and highly toxic CuCN at 100 °C under harsh high vacuum conditions. Prepared by reacting for 24 hours; in the last step of the N-N ring-closing reaction of this route, ten times the chemical equivalent of the reducing agent titanium trichloride and three times the chemical equivalent of the strong base sodium methoxide are required, and the reaction produces a large amount of titanium salt. Difficult, low yield

It can be seen that the reaction conditions of this synthetic route are harsh, and a large amount of CuCN, TiCl 3 Such highly toxic and unsafe and economical reagents are difficult to prepare natural products on a large scale

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