Four‐Component Construction of Coumarin‐Fused Pyrrolo[2,1‐a]isoquinoline: Expedient Synthesis of Lamellarins and Their Regioselective Demethylation

Abstract

Construction of the coumarin-fused pyrrolo[2,1a]isolquinoline skeleton was realized through a four-component reaction between isoquinoline, ethyl bromoacetate, ohydroxybenzaldehyde and nitromethane. This methodology was further extended to the synthesis of lamellarin D trimethyl ether and a formal synthesis of lamellarin D. The controlled demethylation of lamellarin D trimethyl ether yielded dihydroxy and tetrahydroxy lamellarin analogues regioselectively.

A Two-Step Approach to a Hexacyclic Lamellarin Core via 1,3-Dipolar Cycloaddition of Isoquinolinium Ylides to Nitrostilbenes

“…Meanwhile, the formation of the 1,2-diarylpyrrolo­[2,1- a ]­isoquinoline ACDEF fragment of lamellarins (Figure ) dictates the use of unsymmetrical diarylalkynes with electron-donating substituents as dipolarophiles, thus rendering regioselective reaction quite problematic. It is noteworthy that other known syntheses of lamellarins based on 1,3-dipolar cycloaddition (such as the interesting approaches of Wu and Khan) required a separate step for the introduction of the aryl substituent.…”

Diversely functionalized isoquinolines and their core-embedded heterocyclic frameworks: a privileged scaffold for medicinal chemistry

“…Manjappa et al developed a one-pot access to a base mediated four-component reaction to afford coumarin-fused pyrrolo[2,1- a ]isoquinoline 181 (Scheme 36). 80 Cycloaddition of isoquinoline 176 with o -hydroxybenzaldehyde 177 in nitromethane 178 under reflux conditions followed by lactonization with ethyl bromoacetate 179 affords scaffold 181 . Compound 181 shows structural similarity to architecturally interesting antitumor active alkaloid lamellarin D.…”

Cascade Synthesis of Pyrrolo[1,2-a]quinolines and Pyrrolo[2,1-a]isoquinolines via Formal [3 + 2]-Cycloaddition of Push–Pull Nitro Heterocycles with Carbonyl-Stabilized Quinolinium/Isoquinolinium Ylides

“…9 They exhibit a broad spectrum of pharmacological activities, including antitumor and antiretroviral activities, as well as a reversal of multidrug resistance, which has made them attractive synthetic targets in last years. 10 Remarkable examples this class are (S)-(−)-trolline IX and (R)-(+)-oleracein E X, which were isolated from Trollius chinensis and Portulaca oleracea, respectively. 11 (S)-(−)-Trolline exhibits both antibacterial activity against respiratory bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae) and antiviral activity against influenza viruses A and B, 12a while (R)-(+)-oleracein E shows 1,1-diphenyl-2picryl-hydrazyl (DPPH) radical scavenging and antioxidant activities.…”