Total synthesis of cordatanine, structural reassignment of drymaritin, and anti-inflammatory activity of synthetic precursors

Total Synthesis of Bioactive Canthine Alkaloid Cordatanine Comprising in Situ Double Oxidative Aromatization of Tetrahydrocarbazole

“…The obtained analytical and spectral data for cordatanine ( 10 ) were in complete agreement with the reported data. 9,10,14…”

“…11,12 The total synthesis of cordatanine and zanthochilone is a challenging task and is of current interest due to their structural features, potential bioactivities, and the seasonal changes that affect their concentration in natural sources. 8−13 Recently, Wu et al accomplished the synthesis of cordatanine in four steps with an 8% overall yield and unambiguously confirmed its revised structural assignment; 9,10,14 the synthesis of zanthochilone, however, is awaited. In continuation of our studies on the use of cyclic anhydrides to synthesize bioactive natural products, 15−19 we herein report a facile regioselective approach to cordatanine and attempted synthesis of zanthochilone from the readily available common precursors, tryptamine and methoxymaleic anhydride 20 (Schemes 1–4).…”

“…Canthines are an important section of β-carboline alkaloids, and nearly 200 canthinone alkaloids exhibiting a broad range of potential bioactivities have been reported in the literature. , Pentralis (6 H -indolo­[3,2,1- de ]­[1,5]­naphthyridin-6-one) from Figure was first isolated in 1952, and several strategically elegant syntheses of this class of compounds are known in the contemporary literature. − The anti-human immunodeficiency virus alkaloid, cordatanine (4-methoxycanthin-6-one), was isolated from Drymaria cordata in 1986 and then from Drymaria diandra in 2004 (EC 50 0.699 μg/mL). − The antifungal alkaloid, zanthochilone (5-methoxycanthin-6-one), has been isolated from the plant species Zanthoxylum chiloperone var. angustifolium . , The total synthesis of cordatanine and zanthochilone is a challenging task and is of current interest due to their structural features, potential bioactivities, and the seasonal changes that affect their concentration in natural sources. − Recently, Wu et al accomplished the synthesis of cordatanine in four steps with an 8% overall yield and unambiguously confirmed its revised structural assignment; ,, the synthesis of zanthochilone, however, is awaited. In continuation of our studies on the use of cyclic anhydrides to synthesize bioactive natural products, − we herein report a facile regioselective approach to cordatanine and attempted synthesis of zanthochilone from the readily available common precursors, tryptamine and methoxymaleic anhydride (Schemes –).…”

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

“…The canthin-6-one alkaloids have been synthesized via different approaches by many researchers [2,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75]. In order to use these methods to guide our review more clearly, we categorized classic and efficient synthetic methods according to their key reaction steps.…”

Recent Advances in the Synthesis of β-Carboline Alkaloids

“…In the final step, debenzylation of compound 221 led to (−)-39. An alternate synthesis of cordatanine (40) has also been developed (Scheme 27) [138]. Tryptamine (108) was used again as the starting material which underwent a Pictet-Spengler reaction with ethyl glyoxalate (232), followed by direct oxidative aromatization The first total synthesis of natural product griseofamine A (41) together with its diastereomer 16-epi-griseofamine A was described by Pan et al (Scheme 28) [67].…”