A Short Synthesis of Rutecarpine and/or Vasicolinone from 2-Chloro-3-(indol-3-yl)ethylquinazolin-4(3H)-one: Evidence for the Participation of the Spiro Intermediate

Progress in Studies on Rutaecarpine. II.—Synthesis and Structure-Biological Activity Relationships

“…To synthesize rutaecarpine, C-ring construction can be pursued in three different ways via: (1) C 13a -C 13b bond formation; (2) N 6 -C 7 bond formation; or (3) C 8 -C 8a bond formation. Methods involving C 13a -C 13b bond formation at the final stage of synthetic sequences have been most commonly used [1,26,30,31,42,43,44,45,46,47]. However, a method employing C 8 -C 8a bond formation has not been studied as yet.…”

Progress in the Studies on Rutaecarpine

“…It should be noted that the reactions attempted with a relatively poor leaving Cl moiety at C2 of the quinazolinone ring afforded a mixture of products [74]. The distributions of the products 1 a , 22 , 23 , and 24 were highly dependent on the reaction conditions (Table 6).…”

“…The Vilsmeier-Haack reaction on 38 yielded corresponding N , N -dimethylmethylidene compound 39 , which was treated with aniline in refluxing EtOH to give hydrazone 40 in 87% yield. Fischer indole synthesis was then applied to 40 to yield rutaecarpine in 40% over three-step yields via spiro compound 41 (Scheme 17) [74]. …”

Facile One-Pot Synthesis of Quinazoline-2,4-dione Derivatives and Application to Naturally Occurring Alkaloids from Zanthoxylum Arborescens

“…The nucleophilic attack of primary amine of 5 to carbonyl group on the oxazine ring of isatoic anhydride (4) followed by loss of carbon dioxide produced compound 6. The structural assignment of 6 was confirmed by 13 C NMR, which clearly showed a carbonyl peak of amide group at 168.9 ppm. To give the quinazoline-2,4-dione moiety, reaction of isatoic anhydride (4) and tryptamine (5) with triphosgene was next attempted.…”

“…The ring opening of 4 with amines has already been described by another group. 13 The aminobenzamide 6 was cyclized using triphosgene in the presence of a base through the intermediate 16 to give product 7. The existence of the isocyanate intermediate formed from the reaction of aminobenzamide and triphosgene has also been proven by Eckert.…”