Synthesis of Pyrrolo[2,1‐a]isoquinoline Class of Natural Product Crispine A

Abstract

As a naturally occurring small-molecule, various optical isomers of chiral pyrrolo[2,1-a]isoquinoline alkaloid crispine A represent a potential class of chiral molecules in contemporary organic chemistry, and possess diverse biological activities. The range of pharmacological activities include antidepressant, antiplatelet, antileukemic, and anticancer activities. This review provides an overview of the literature on the strategies, employed in the synthesis of crispine A in their racemic and enantiopure forms via Bischler-Napieralski cyclization, Pictet-Spengler cyclization, N-Alkylation/Acylation-cyclization, Oxidative cyclization, and Asymmetric hydrogenation in the period of 1931-2021. This study accentuates the need for the developing more effective synthesis, and search for involved biological applications for the pyrroloisoquinoline class of natural product. Attention has been drawn towards the use of relatively less documented but easily accessible naturally occurring diastereomeric scaffolds namely, garcinia and hibiscus acids. These lactones obtained from (+)and (À )-2-hydroxycitric acids bearing chemically amenable functional groups are investigated as an ideal choice for the enantiopure synthesis of the (À )-(R)-and (+)-(S)-Crispine A structural frame work.

Synthesis of mono-fluorinated heterocycles with a ring-junction nitrogen atom via Rh(iii)-catalyzed CF3-carbenoid C–H functionalization and defluorinative annulation

“…12 A number of different strategies have been utilized to synthesize this important class of polycyclic N-heterocycles. 13 Among them, transition metal-catalyzed [4 + 2] annulations of 2-aryl indoles with 2C-units are attractive due to the step- and atom-economy of C–H activation reactions. 14 Recently, acyl substituted α-diazoacetates have been developed as efficient 2C-units for the construction of various N-heterocycles via Rh-catalyzed sequential carbenoid functionalization and intramolecular condensation processes.…”

Photocatalytic Oxidative [3+2] Cycloaddition for Pyrrolo[2,1‐a]isoquinoline Synthesis Using a Porphyrin‐Based Covalent Organic Framework

“…Pyrrolo[2,1‐ a ]isoquinolines are important scaffolds which are widely found in natural products and pharmaceutically important synthetic molecules [1–5] . Plenty of alkaloids containing pyrrolo[2,1‐ a ]isoquinoline moieties exhibited unique bioactivities such as antitumor activity, antibiotic activity, antidepressant activity, HIV integrase inhibition, cell division inhibition, and tubulin polymerization inhibition.…”

“…Pyrrolo [2,1-a]isoquinolines are important scaffolds which are widely found in natural products and pharmaceutically important synthetic molecules. [1][2][3][4][5] Plenty of alkaloids containing pyrrolo[2,1-a]isoquinoline moieties exhibited unique bioactivities such as antitumor activity, antibiotic activity, antidepressant activity, HIV integrase inhibition, cell division inhibition, and tubulin polymerization inhibition. Therefore, great efforts have been devoted to the development of methodologies for the construction of pyrrolo[2,1-a]isoquinolines, including electrocyclization pathway, double-barreled Heck cyclization, and so on.…”

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

“…There is a profound increase in research reports published yearly on the synthetic accomplishments in constructing the complex structures of the isoquinoline skeleton in non-racemic and enantiopure forms. 27–31 The studies on isoquinoline scaffolds offer new opportunities in medicinal and bioorganic chemistry due to their therapeutic applications. 32–35 Novel synthetic methodologies are reported in constructing isoquinoline skeletons instead revolving around the traditional Pictet–Spengler, Bischler–Napieralski, Pomeranz–Fritsch, and Bobbitt reaction procedures.…”