122419-52-7Relevant academic research and scientific papers
Total synthesis of (±)- and (-)-actinophyllic acid
Martin, Connor L.,Overman, Larry E.,Rohde, Jason M.
supporting information; experimental part, p. 4894 - 4906 (2010/06/18)
Development of efficient sequences for the total syntheses of (±)-actinophyllic acid (rac-1) and (-)-actinophyllic acid (1) are described. The central step in these syntheses is the aza-Cope/Mannich reaction, which constructs the previously unknown hexacyclic ring system of actinophyllic acid in one step from much simpler tetracyclic precursors. The tetracyclic hexahydro-1,5-methano-1H-azocino[4,3-b]indole ketone rac-37 is assembled from o-nitrophenylacetic acid in four steps, with oxidative cyclization of a dienolate derivative of tricyclic precursor rac-35 being the central step. In the first-generation synthesis, this intermediate is transformed in two steps to homoallyl amine rac-43, whose formaldiminium derivative undergoes efficient aza-Cope/Mannich reaction to give pentacyclic ketone rac-44. In four additional steps, this intermediate is advanced to (±)-actinophyllic acid. The synthesis is streamlined by elaborating ketone rac-37 to β-hydroxyester intermediate rac-53, which is directly transformed to (±)-actinophyllic acid upon exposure to HCl and paraformaldehyde. This concise second-generation total synthesis of (±)-actinophyllic acid is realized in 22% overall yield from commercially available di-tert-butyl malonate and o-nitrophenylacetic acid by a sequence that proceeds by way of only six isolated intermediates. The first enantioselective total synthesis of (-)-actinophyllic acid (1) is accomplished by this direct sequence from tricyclic keto malonate (S)-35. Catalytic enantioselective reduction of α,β-unsaturated ketone 66 is the key step in the preparation of intermediate (S)-35 from the commercially available Boc-amino acid 65. Discussed also is the possibility that the aza-Cope/Mannich reaction might be involved in the biosynthesis of (-)-actinophyllic acid.
214. Synthesis of Esters of 3-(2-Aminoethyl)-1H-indole-2-acetic Acid and 3-(2-Aminoethyl)-1H-indole-2-malonic Acid (=2-propanedioic Acid
Mahboobi, Siavosh,Bernauer, Karl
, p. 2034 - 2041 (2007/10/02)
Alkyl 3-(2-aminoethyl)-1H-indole-2-acetates 6a and 6b are synthesized starting from methyl 1H-indole-2-acetate (2) via methyl 3-(2-nitroethenyl)-1H-indole-2-acetate (4) and the alkyl 3-(2-nitroethyl)-1H-indole-2-acetates 5a and 5b (Scheme 1).Analogously, diisopropyl 3-(2-aminoethyl)-1H-indole-2-malonate 20b is obtained from diisopropyl 1H-indole-2-malonate 11 c (Scheme 4).An alternative synthesis of 20a and 20b follows a route via 15-18 and the dialkyl 3-(2-azidoethyl)-1H-indole-2-malonates 19a and 19b, respectively (Scheme 3).The aminoethyl compounds 6a and 20a are easily transformed into lactams 7 and 21, respectively.Procedures for the preparation of the indoles 2 and 11a and of the alkylating agent 14 are described.A tautomer 12 of 11a is isolated.
