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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 (−)‐2‐hydroxycitric acids bearing chemically amenable functional groups are investigated as an ideal choice for the enantiopure synthesis of the (−)‐(R)‐ and (+)‐(S)‐Crispine A structural frame work. [ABSTRACT FROM AUTHOR]

The development of palladium-catalyzed α-arylation of carbonyl compounds has emerged as a new avenue in the design of new routes for the synthesis of natural products and active pharmaceutical ingredients (APIs). In many cases, syntheses based on α-arylation strategies provide elegant routes in terms of increasing the overall yields, improving the synthesis scope, and decreasing the number of steps. This microreview aims to highlight the importance of palladium-catalyzed α-arylation methodologies, covering a range of notable reported examples of the total syntheses of structurally important compounds, thereby highlighting the importance of this powerful methodology for key steps in organic synthesis. [ABSTRACT FROM AUTHOR]

Cover Feature: Synthesis of Pyrrolo[2,1-a]isoquinoline Class of Natural Product Crispine A (Eur. J. Org. Keywords: Alkaloids; Crispine A; Natural product; Pyrrolo[2,1-a]isoquinoline; Synthetic Methods; Total synthesis EN Alkaloids Crispine A Natural product Pyrrolo[2,1-a]isoquinoline Synthetic Methods Total synthesis 4896 4896 1 09/29/21 20210921 NES 210921 B The Cover Feature b shows naturally occurring (2 I S i ,3 I S i )- and (2 I S i ,3 I R i )-tetrahydro-3-hydroxy-5-oxo-2,3-furan dicarboxylic acid bearing, chemically amenable functional groups that are an ideal choice for the enantiopure synthesis of the (-)- and (+)-Crispine A, respectively. Alkaloids, Crispine A, Natural product, Pyrrolo[2,1-a]isoquinoline, Synthetic Methods, Total synthesis. [Extracted from the article]

Rapid reaction of NaBH 4 with MeOH precludes its use as a solvent for large-scale ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %) stabilizes NaBH 4 solutions in methanol at 25 °C and permits the use of these solutions for the reduction of esters to alcohols. The generality of this reduction method was demonstrated using 22 esters including esters of naturally occurring chiral γ-butyrolactone containing dicarboxylic acids. This method permits the chemoselective reductions of esters in the presence of cyano and nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical and chemical yields. Lactones, aliphatic esters, aromatic esters containing electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than aryl esters containing electron-donating groups. The 11 B NMR spectrum of the NaOMe-stabilized NaBH 4 solutions showed a minor quartet  due to monomethoxyborohydride (NaBH 3 OMe) that persisted up to 18 h at 25 °C. We postulate that NaBH 3 OMe is probably the active reducing agent. In support of this hypothesis, the activation barrier for hydride transfer from BH 3 (OMe) - onto benzoic acid methyl ester was calculated as 18.3 kcal/mol.