β‐Carbolin‐Alkaloide, I. Synthese von 1‐Aryl‐ und 1‐Alkenyl‐β‐carbolinen durch Palladium‐katalysierte Kupplungsreaktionen

Abstract

1-Chloro-P-carboline (6) is prepared in three steps starting komaroine (11) and perlolyrine (15). Pavettine (16) is prepared from tryptamine (3). Palladium-catalyzed coupling reactions of by coupling of 6 with tributylvinylstannane. 6 with aryl boronic acids offer an easy access to the alkaloids ,,Einfache" P-Carbolin-Alkaloide ['] Diese neuartigen Kupplungsreaktionen bieten neben den meist hohen Ausbeuten den Vorteil, da13 eine groBe Zahl von funktionellen Gruppen toleriert wird und so auf die bei vielen anderen C -C-Kniipfungsreaktionen erforderlichen Schutzgruppentechniken verzichtet werden kann..Fur die oben beschriebene Synthesestrategie sollten 1-Iod-und 1-Brom-P-carbolin (2, Hal = I/Br) die geeignetsten Kupplungspartner sein. Problematisch ist aber, daB iodierte und bromierte n-Mangel-Heteroaromaten relativ schwierig herzustellen sind. Wesentlich besser zuganglich sind die entsprechenden Chlorverbindungen. Deshalb wurde als zentrale Zwischenstufe fur die Alkaloidsynthesen 1-Chlor-Pcarbolin (6) ausgewahlt. Auch diese Verbindung sollte, da

The Gramine Route to Pyrido[4,3-b]indol-3-ones – Identification of a New Cytotoxic Lead

“…So we worked out efficient strategies for the construction of 1-oxo-β-carbolines [3–6] and hybrids between 1-oxo-β-carbolines and other alkaloids [7]. …”

A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

“…A majority of alkaloids are substituted at the 3-position of β-carbolinones, and two major synthetic strategies have been adopted for this purpose: one approach starting from tryptamine which offers an easy access to β-carbolinone (9 H -pyrido[3,4- b ]indol-1(2 H )-one, Scheme 1) [25], and another three step route to synthesize 3-aryl-β-carbolinone by reaction of chalcone derivatives with N -acetyl-2-cyanoglycine ethyl ester (Scheme 2) [26]. Nevertheless, it is still difficult to introduce other groups directly at the 3-position of the β-carbolinone by these methodologies, especially for the synthesis of electron-withdrawing substituents at the 3-position of β-carbolinone.…”

Efficient synthesis of eudistomin U and evaluation of its cytotoxicity

“…15 Following Bracher and Hildebrand’s conditions for the synthesis of komaroine and perlolyrine, 11 we obtained an initial yield of 38%. Seeking to optimize this reaction yield, we tested conditions that varied the solvent, palladium precatalyst, and exogenous base (Table 1).…”

“…In our synthesis of eudistomin U reported herein, we modified the approach of Bracher and Hilderbrand, who successfully employed this strategy in the synthesis of naturally occurring 1-aryl-β-carbolines. 11 …”

“…11 Attempts to oxidize lactam 3 to the unsaturated pyridone 4 were unsuccessful using Pd/C or Ce(NH 4 ) 2 (NO 3 ) 6 . DDQ oxidation, however, provided 4 in a crude yield of 94% and was taken directly to the next step without further purification.…”