Regiospecific Synthesis of Mono-N-substituted Indolopyrrolocarbazoles

Abstract

[reactions: see text] Two complementary and efficient strategies have been developed for the regiospecific synthesis of unsymmetrical indolopyrrolocarbazoles (IPCs) mono-N-substituted with a pentacycle. A halogen in position 2 of the intermediate bisindolylmaleimides 3a-e allows a selective Mitsunobu coupling by exploiting the increased acidity of the 2-chloro-substituted indole nitrogen. It also promotes an easier cyclization of bisindolylmaleimides 4a-e and 7b-e to IPCs. Alkylation of the 2-unsubstituted indole-3-carboxamides 2a,b and further processing to the corresponding IPCs gives access to the opposite regioisomers.

In Vivo Active Aldosterone Synthase Inhibitors with Improved Selectivity: Lead Optimization Providing a Series of Pyridine Substituted 3,4-Dihydro-1H-quinolin-2-one Derivatives

“…The following compounds were prepared according to previously described procedures: 6-bromo-1,2,3,4-tetrahydronaphthalen-2-ol (2a), 21 6-bromo-3,4-dihydroquinolin-2(1H)-one (12a), 24 5-bromo-1,3-dihydro-2H-indol-2-one (13a), 25 6-bromo-8-nitro-3,4-dihydroquinolin-2(1H)-one (18a). 27 Synthesis of the Target Compounds.…”

“…The initial bromination procedures yielding either 12a or 13a have been described previously. 24,25 Subsequent N-alkylation was accomplished by treating the quinolinones with alkyl halide and potassium tert-butylate in dimethylformamide to afford the intermediates 14a-16a. 26 A nitro substituent was selectively introduced in the 8-position of 10a by treating with a mixture of concentrated sulfuric acid and concentrated nitric acid to yield 18a.…”

Synthesis of non glycosidic nucleobase-sugar mimetics

“…The envisioned modular strategy (Chart 1), allows the access to chemical diversity via the opening of two epoxides, enantiomerically pure 3 [6a] and racemic 4 (The epoxide 4 was obtained by epoxidation of trans 4-tertbutyl-dimethyl-silanyloxy)-cyclopent-2-enol [7] (see the experimental section) with different anilines. Further Nfunctionalization and Pd-catalyzed ring formation yield the target nucleobase-sugar mimics.…”

“…Epoxide 4 confirmed its overall lower activity, even under stronger reaction conditions, and did not react with deactivated anilines 5 g and 5 h (entries 11-12). Yields obtained with anilines 5cf were nevertheless good (entries [7][8][9][10]. Results are reported in Table 2.…”

Protecting-group-free synthesis of the bisindolylmaleimide GF109203X

“…Later on, Faul et al 18 developed a more efficient synthesis of GF109203X in 51% yield starting from indole, using an O-trityl (Tr) protecting group (Scheme 1). The binsindolylmaleimide core was made via the coupling 19 between 12 and 13, and the side-chain was introduced by Nalkylation of indole-acetamide 14 at an early stage. Although protecting groups play an important role in organic synthesis, 20 their inclusion in a synthetic route increases the total number of steps by needing protection and deprotection and decreases atom-economy.…”