Biomimetic Synthesis and Biological Evaluation of Aplidiopsamine A

Abstract

The first total synthesis of Aplidiopsamine A, a rare 3H-pyrrolo[2,3-c]quinolone alkaloid from the Aplidiopsis confluata, has been achieved following the proposed biosynthesis. This biomimetic synthesis requires only 5 steps and proceeds in 20.8% overall yield. Biological evaluation across large panels of discrete molecular targets identified that Aplidiopsamine A is a highly selective PDE4 inhibitor, a target for numerous CNS disorders.

Tandem Cyclization−Annulation of α‐Acidic Isocyanides with 2‐Methyleneaminochalcones: Synthesis of Pyrrolo[2,3‐c]quinoline Derivatives

“…[5] The rare and unique structural feature and interesting bioactive properties of these heterocycles inspired continuous interest in developing efficient protocols for their preparation. [6][7][8][9][10][11] The wellestablished strategy is the formation of central pyridine ring from aryl-substituted pyrroles by Morgen-Walls reaction, [6] PictetÀSpengler reaction, [7] tandem reductive cyclization reaction, [8] Pd-catalyzed imine cyclization, [9] Bischler-Napieralski-type cyclization [10] and areneÀynamide cyclization. [11] Alternatively, methods involving the synthesis of pyrrole ring by Bartoli indolization [12a] or reductive cyclization reaction [12b,c] have also been documented.…”

Synthesis of 4‐Substituted Pyrrolo[2, 3‐c]quinolines via Microwave‐Assisted C‐N Bond Formation

“…A biomimetic approach was put forward for the synthesis of aplidiopsamine A (Figure ), a well pyrrolo[2, 3‐ c ]quinoline natural product, by Panarese and Lindsley . Here, key precursor aminophenylpyrrole was synthesised by Suzuki coupling between boronate ester and 2‐iodoaniline in the presence of Pd(OAc) 2 .…”

“…A biomimetic approach was put forward for the synthesis of aplidiopsamine A (Figure 1), a well pyrrolo[2, 3-c]quinoline natural product, by Panarese and Lindsley. [7] Here, key precursor aminophenylpyrrole was synthesised by Suzuki coupling between boronate ester and 2-iodoaniline in the presence of Pd(OAc) 2 . Further sequence of reactions starting from TIPS deprotection, reactions with a-bromoacetyl bromide and adenine led to the formation of aplidiopsamine A in 45% yield.…”

Copper-catalyzed heteroannulation: a simple route to the synthesis of pyrrolo[2,3-b]carbazole and pyrrolo[2,3-b]quinoline derivatives

“…5 Many synthetic methods are being developed towards the pyrroloquinolines which are core structures in many important alkaloids. [6][7][8][9][10][11] It should be noted that there are tremendous application of pyrroloquinoline quinone (PQQ), also termed as methoxatin (2,7,9,-tricarboxy-lH-pyrrolo(2,3-f)quinoline-4,5-dione) ( fig. 1, 4).…”

“…Aplidiopsamine A, from the temperate Australian ascidian Aplidiopsis confluata, which is the first alkaloid having tricyclic aromatic substructure 3H-pyrrolo[2,3-c]quinoline conjugated to an adenine. 9 Only a few methods exist towards the synthesis of these molecules. In this context, development of synthetic routes for various functionalized pyrrolocarbazoles and pyrroloquinolines is important.…”