Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine

Abstract

This study reveals an alternative sequence for the synthesis of compounds that contain the pyrrolodiketopiperazine structural motif. Starting with a diketopiperazine precursor, a mild aldol condensation precedes pyrrole annulation and bicyclic ring fusion. The derived intermediate aldol condensation products, which bear either a protected carbonyl or a functionalized alkyne, can be cyclized to the pyrrolodiketopiperazine by protic or gold Lewis acid catalysis.

Pyrrole‐Fused Benzoxazinones/Quinoxalinones: Molecular Dynamic Simulation, Antiproliferative and Antibacterial Activities

“…A large number of pyrrole fused heterocyclic compounds have been investigated as cytotoxic agents against numerous cancer cell lines including breast cancer cell lines [13b,20] . In our previous report a protocol was developed by our team for the synthesis of pyrrole fused benzoxazinones/quinoxalinones as depicted in Table 1 [19] .…”

A Review of the Synthetic Strategies toward Dihydropyrrolo[1,2-a]Pyrazinones

“…Diketopiperazines 113 underwent base-catalyzed aldol condensations with different aldehydes, affording adducts that, in the case of acetal substituents, as for 114, underwent camphorsulfonic acid (CSA)-mediated cyclization on heating in toluene to pyrrolodiketopiperazines 116. The aldol condensation products 115 resulting from alkynyl aldehydes underwent gold-catalyzed cyclization under similar conditions, giving an alternative preparation for compounds 116 with a larger scope of R 1 -substituents [116] (Scheme 31). Diketopiperazines 113 underwent base-catalyzed aldol condensations with different aldehydes, affording adducts that, in the case of acetal substituents, as for 114, underwent camphorsulfonic acid (CSA)-mediated cyclization on heating in toluene to pyrrolodiketopiperazines 116.…”

Flexible Construction of Functionalized‐Pyrroles under Palladium or Copper Catalysis in the Presence of BF3 ⋅ Et2O

“…This strategy generally requires the use of stereodefined tri‐ or tetrasubstituted ( Z )‐enynamines or ( Z )‐enynols as substrates, while the synthesis of such starting materials is quite challenging and thus correspondingly leading to the formation of pyrrole products with limited functionalities. In order to overcome the challenge of controlling stereoselectivity toward the formation of ( Z )‐enynamine or related intermediates, cyclic starting substrates [6n–q] had to be utilized and correspondingly resulted in bicyclic pyrroles. The synthesis of pyrroles could also be achieved with the use of 1‐en‐4‐yn‐3‐ols while suffering with low yields (typically <50%), quite limited substitution patterns (most methyl functionality) and high reaction temperature (100 °C) [7] .…”