Total Synthesis and Biological Activity of Marine Alkaloid Eudistomins Y1–Y7 and Their Analogues

Abstract

Eudistomin Y class compounds are a series of β-carbolines which was originally isolated from a marine turnicate or ascidian near the South Korea Sea. These compounds contain bromo-substituted groups, which is one of the typical characters of marine natural products. We report herein the chemical synthesis and biological evaluation of seven new β-carboline-based metabolites, Eudistomins Y1–Y7, and their hydroxyl-methylated phenyl derivatives. Using bromo-substituted tryptamines and bromo-substituted phenylglyoxals as the key intermediates, Eudistomins Y1–Y7 and their derivatives were synthesized via the acid-catalyzed Pictet-Spengler reaction and fully characterized by 1H- and 13C-NMR and mass spectroscopy. Biological studies revealed that all of the compounds showed moderate growth inhibitory activity against breast carcinoma cell line MDA-231 with IC50 of 15–63 μM and the inhibitory activities of hydroxyl-methylated phenyl products were higher than that of the corresponding natural products Eudistomins Y1–Y7.

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

“…Jenkins and co-workers reported the synthesis of fascaplysin ( 4 ) by the reaction of tryptamine with phenylacetyl chloride and carried out the aromatization under photo-oxidation conditions [15–16]. Lindsley and co-workers [17] reported the synthesis of eudistomins Y 1 −Y 7 ( 6a – 6g ) under microwave conditions [18]. Considering the complexity involved in the synthesis of several of the starting materials used in the preparation of carbolines, especially tricarbonyl compounds, an alternate approach for the synthesis of 3 H -β-carboline is sought after.…”

An efficient synthesis method targeted to marine alkaloids marinacarbolines A–D and their antitumor activities

“…The modification method is to use p-toluenesulfonic acid as the acid catalyst to make the cyclization and aromatization in one step to form b-carboline directly with the reaction between L-tryptophan and different appropriate aldehydes [6]. This strategy for the construction of the b-carboline derivatives is efficient and straightforward, and based on the principle, we previously accomplished the total syntheses of marine alkaloid pityriacitry [6] and eudistomins Y 1 -Y 7 [7].…”

“…Given our longstanding interest in the b-carboline alkaloids [7] and the intriguing biological profile of marinacarbolines A -D, we undertook the development of a scalable total synthesis of marinacarbolines A -D to provide sufficient quantities for additional biological evaluation.…”

Recent Advances for the C–C and C–N Bond Formation in the Synthesis­ of 1-Phenethyl-tetrahydroisoquinoline, Aporphine, Homoaporphine­, and β-Carboline Alkaloids

“…Although the series of eudistomins Y1-Y7 have been prepared by other methods, such as benzylic oxidation/aromatization promoted by 2-iodoxybenzoic acid, 137 the benzylic oxidation catalyzed by DBU of dihydro-β-carbolines, 138 and tandem C-N/C-C bond formation and aromatization between tryptamines and glyoxal derivatives. 139 Perhaps the most efficient method is the tandem iodinemediated oxidation between tryptamines 216 and acetophenones 217, where C-N/C-C bond formation and aromatization proceed smoothly to give eudistomins Y1-Y6 218-223 in one step in 58-78% yields (Scheme 37). 140…”