Synthese von Tuboflavin, 4‐Äthyl‐canthin‐6‐on und Canthin‐6‐on

Abstract

~ Kondensation von (&)-Tryptophan rnit (+)-khylbernsteinsaureanhydrid fdhrte zu einemGcmisch der beiden Acylaminosauren 2 und 6. Die reinc Saure 2 gab beim Erhitzcn mit einem Gemisch von Polyphosphorsaure, Phosphoroxychlorid und V205 zur Hauptsachc das bereits bekannte 4-khylcanthin-6-on (3). Das daraus bereitetc 4-khylcanthin (5) lieR sich durch Sclcndioxyd in 3 zuriickfiihren. Oxydative Cyclisierung von 6 und nachfolgende Hydrierung des Cyclisationsproduktes gab 5-khyl-4.5-dihydrocanthin-6-on (7), das iiber 8 in das Alkaloid Tuboflavin (1) umgewandelt werden konnte. Die glcichc Cyclisierung mit (*)-Succinyltryptophan fiihrte zum Alkaloid Canthin-6-on (10). Vor einiger Zeit wurde uber die Isolierung und Strukturaufklarung des Tuboflavins, eines Nebenalkaloides aus der Rinde von

A convenient approach to the canthin‐4‐one ring system: Total synthesis of the alkaloids tuboflavine and norisotuboflavine

“…Up to now several multi‐step syntheses of the alkaloids tuboflavine [11], isotuboflavine [7], norisotuboflavine [7, 12], and of unsubstituted canthin‐4‐one [7] have been published, but none of these offer overall yields higher than 1%. So these total syntheses could only serve as proofs for the structures of the alkaloids, but do not represent efficient approaches to the canthin‐4‐one ring system.…”

“…Recrystallization from CH 2 Cl 2 ‐heptane gave pale yellow needles, mp 294°C (lit. [7, 9, 11]: mp (diethyl ether) 298–300°C, (methanol) 282–284°C, (methanol) 294–296°C); IR: 1633, 1607, 1496, 1428, 1289, 1220 cm −1 ; 1 H NMR (deuteriochloroform) δ 8.92 (d, 1H, J = 4.7 Hz, 2‐H), 8.08 (d, 1H, J = 7.7 Hz, 11‐H), 7.99 (d, 1H, J = 4.7 Hz, 1‐H), 7.83 (d, 1H, J = 8.4 Hz, 8‐H), 7.60 (m, 1H, 9‐H), 7.42 (dd, 1H, J = 7.5, 7.6 Hz, 10‐H), 6.35 (s, 1H, 5‐H), 2.87 (s, 3H, CH 3 ); 13 C NMR (DMSO‐d 6 ) δ 178.8 (CO), 147.0 (C‐6), 146.7 (C‐2), 140.1 (C‐7a), 138.5 (C‐3a), 135.4 (C‐11c), 133.4 (C‐11b), 130.9 (C‐9), 125.4 (C‐11a), 124.6 (C‐10), 123.7 (C‐11), 118.2 (C‐1), 117.6 (C‐5), 114.4 (C‐8), 21.3 (CH 3 ); ms (EI) m/z 234 (M + , 100), 217 (15), 195 (25), 168 (62), 139 (22) and 113 (27); Anal. Calcd.…”

Fruitful Decades for Canthin-6-ones from 1952 to 2015: Biosynthesis, Chemistry, and Biological Activities

“…The use of the Bischer-Napieralski reaction to synthesize canthin-6-one alkaloids was first reported in 1966 [27], and Soriano-Agaton et al reported a more recent synthesis in 2005 (Scheme 3) [2]. The overall yield of canthin-6-one in the later synthesis was increased to 76.83% in four steps by Soriano-Agaton.…”

“…Based on the biosynthetic line of canthin-6-one alkaloids, the infractine-functionalized and nanoparticle-supported biomimetic synthesis of canthin-6-one was accomplished [26]. The first total synthesis of canthin-6-one ( 1 ), which was achieved with a poor overall yield via a classic Bischer-Napieralski method, was reported in 1966 [27]. In 2013, Hollis Showalter et al reviewed the synthetic approaches to canthin-6-ones and their ring-truncated congeners [28], their review including almost all reported cases.…”

Years with Hans Schmid

“…We three were hard working and became good friends, also outside the university. My first research place was in Lab 17, [14] close to the bench of Hans Jürgen Rosenkranz, who had started his PhD work on the synthesis of tuboflavine and analogues already end of 1963 [15] and where Janos had his bench. Georg, Janos, and I, we formed a sort of mechanistic troika, with new ideas every day and endless discussions, since the Woodward-Hoffmann rules had been published just that summer in J. Amer.…”