Method for synthesizing alkaloid

Abstract

The invention discloses a method for synthesizing alkaloid Onychine, comprising the following steps: (1) under the action of a metal salt catalyst, indenone and 2-butine-1-amine generate 4-methyl-5H-indeno(1, 2-b) naphthyridine by a series of reactions; wherein, the dosage of the 2-butine-1-amine is 1.0 to 3.0 equivalent of the indenone; a catalyst is Au salt or platinum salt; the dosage of the catalyst is 0.01 to 1.0 equivalent of the indenone; (2) C-H at the benzyl position of the 4-methyl-5H-indeno(1, 2-b) naphthyridine is selectively oxidized to a keto carbonyl group, so as to generate the Onychine; the 4-methyl-5H-indeno(1, 2-b) naphthyridine is selectively oxidized by a selective C-H bond to generate the Onychine; and an oxidizer is a metal oxidant of potassium permanganate, chromium trioxide or the combination between metal cupric salt, malysite, dioxygen and peroxide.

Description

A kind of synthetic method of alkaloid 1. Technical field The invention relates to a methodology for forming a novel carbon-carbon bond and carbon-nitrogen bond catalyzed by a transition metal and a total synthesis method for 4-azafluorenone natural alkaloid Onychine. 2. Background technology Onychine is a natural alkaloid with the structure of 5H-indeno[1,2-b]pyridin-5-one, which mainly exists in the species of Annonaceae. Some 5H-indeno[1,2-b]pyridin-5-one alkaloids substituted with hydroxyl and methoxy groups on ring A have been discovered one after another, and have been tested to have obvious anti-candida and fungal activities. (DeAlmeida, M.E.I.; Braz, F.R.; von Bulow, M.V.; Gottleib, O.R.; Maia, J.G.S. Phytochemistry 1976, 15, 1186. Arango, G.J.; Cortes, D.; Cassels, B.K.; Cave, A.; Merienne, C. Phytochemistry 1987, 26, 2093.) Structural formula one Chemists' initial interest in the synthesis of this type of alkaloids with a 6-5-6 tricyclic structure stems fr...

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Problems solved by technology

From the synthesis methods summarized above, it can be seen that: (1) high temperature pyrolysis ring closure reaction or Diels-Alder ring formation reaction from indene structure substrates face harsh conditions, low yield and poor reaction regioselectivity (usually accompanied by by-products 2 -Methyl-5H-indeno[1,2-b]pyridine) and other shortcomings; (2) the synthesis of Onychine from substituted pyridine requires strong acid and strong base conditions, and the source of substrates is limited; (3) the use of chain bottom The step-by-step method of forming rings is tedious, and the synthesis efficiency is not high

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