Notiz über die Synthese von Iso‐, Noriso‐ und Desäthyl‐tuboflavin

Abstract

Summary. Treatment of 4,5-dihydrocanthin-6-one (V) (prepared from synthetic canthinone (IV)) with ethyl or methyl magnesium iodide and methanolic hydrochloric acid yielded the ethyl or methyl compounds VI and IX. Oxidation of the latter compounds with selenium dioxide in dimethylformamide gave rise to the Pleiocavpa alkaloids isotuboflavine (11) and norisotuboflavine (111) in low yields. Deethyltuboflavine (VIII) was isolated as a byproduct from further oxidation of norisotuboflavine.Aus der Apocynacee Pleiocarfia mutica BENTHAM sind bisher die folgenden vier /?-Carbolin-Alkaloide isoliert worden : Flavocarpin [2], Tuboflavin (I) [3], Isotuboflavin (11) [4] und Norisotuboflavin (111) [4]. Die beiden erstgenannten Pflanzenbasen sind auch synthetisch erhalten worden ( Andere Oxydationsmittel erwiesen sich entweder als wirkungslos oder als zu weitgehend. Schliesslich gelang es, das gesuchte Isotuboflavin (11) in der allerdings bescheidenen Ausbeute von 6,3% durch Oxydation von VI mit Selendioxid in Dimethylformamid (DMF) bei 80" zu gewinnen. Wir nehmen an, dass dabei zunachst das 4-0x0-Derivat von VI entsteht, welches unter Methanolabspaltung in I1 ubergeht. Das synthetische Produkt, gelbe Nadeln vom Smp. 268-270°, erwies sich auf Grund des 1R.-, UV.-und Massenspektrums als identisch rnit naturlichem [4] Isotuboflavin.

Synthesis of Canthin-4-ones and Isocanthin-4-ones via B Ring Construction

“…Calcd for C 14 H 10 N 2 O: C,75.66;H,4.54;N,12.60. Found: C,75.70;H,4.48;N,2,7]naphthyridin-4-one (10a) (one-pot procedure). A mixture of naphthyridinone 15 (225.1 mg, 1.0 mmol), 2chlorophenylboronic acid (235.0 mg, 1.5 mmol), K 2 CO 3 (277.0 mg, 2.0 mmol), and PdCl 2 (dppf)•DCM (5 mol %) in dioxane/H 2 O (75:25, 10 mL) was heated to ∼88 °C (reflux) for 15 min until the starting naphthyridinone 15 had been completely consumed (as determined by TLC).…”

“…20 Synthesis of Meldrum's Acid Ylidenes. -2,2-dimethyl-1,3-dioxane-4,6-dione (1 1481m, 1462m, 1427m, 1400m, 1371m, 1350w, 1304m 1292m, 1246w, 1219m, 1155w, 1177w, 1113m, 1092m, 1059m, 1040m, 993m, 955w, 862m, 835m, 816m, 764s, 735m, (7). To a solution of 4-(2-chlorophenyl)-8-methoxy-1,5-naphthyridine (6) (128.3 mg, 0.47 mmol) in dioxane (2.5 mL) was added concentrated HCl/ H 2 O (50:50) (3.6 mL), and the mixture was heated to ∼101 °C (reflux) until the starting material had been completely consumed (45 min, as determined by TLC).…”

“…The latter was only recently isolated from a mutant ΔstnK4 of Streptomyces f locculus CGMCC4, and its structure elucidated by extensive one-and two-dimensional nuclear magnetic resonance (NMR). 5 Several syntheses for norisotuboflavine, 6 isotuboflavine, 7 and tuboflavine 8 have been reported. In 1966, Schmid et al reported a four-step synthesis for tuboflavine, starting from tryptophan in 0.3% overall yield, 7 while in 1968, they reported the syntheses of norisotuboflavine and isotuboflavine, 6 in three steps starting from 4,5-dihydrocanthin-6-one in <1% overall yield.…”

“…5 Several syntheses for norisotuboflavine, 6 isotuboflavine, 7 and tuboflavine 8 have been reported. In 1966, Schmid et al reported a four-step synthesis for tuboflavine, starting from tryptophan in 0.3% overall yield, 7 while in 1968, they reported the syntheses of norisotuboflavine and isotuboflavine, 6 in three steps starting from 4,5-dihydrocanthin-6-one in <1% overall yield. An alternative five-step synthesis for norisotuboflavine was also reported by McEvoy and Allen, starting from the natural product benzalharman with an overall yield of <1%.…”