Pyrrolines

Introduction

Pyrrolines, also called as dihydropyrroles, have three ismoers with different positions of double bond with empirical formula C4H7N (Fig.1). The hydrogenation of aromate pyrrole can afford Pyrrolines easily. Among the isomers, both 2-pyrroline and 3-pyrroline are cyclic amines, while 1-Pyrroline is a cyclic imine. Pyrrolines, nitrogen-containing five-membered heterocycles, are common structural scaffolds in natural products and pharmaceutical agents. Pyrroline derivatives include natural and synthetic compounds with notable biological and pharmacological properties. Pyrrolines are intermediates in the syntheses of biologically active pyrroles and Pyrrolines. Examples of medicinally important pyrroline-based compounds include protein kinase inhibitor staurosporine and geranylgeranyltransferase inhibitor.

Pyrrolines Fig. 1 The structures of pyrrolines isomers

Applications

Organic Synthesis:

Cyclic imines have proven to be valuable intermediates forthe synthesis of alkaloid natural products. 2-Alkyl-1-pyr-rolines have been used as synthons for halopyrroles which exhibit strong antibacterial, antifungal, and herbicidal activ-ity as well as for pyrrole-2-carboxylates which are trailpheromones of leafcutter ants. Even seldom drugs contain pyrrolines structure, they serve as highly important synthons for the synthesis of other valuable compound applied in medicines. Reaction of ketimines and aldimines in the 1-pyrrolinesseries with ketenes leads to carbapenams 2, N-acylated 2-pyr-rolines 3, and ω-acylamino ketones 4, respectively (Fig.2). Using Dane’s salt carbapenams 5 with vinylamino side chains are available. Some of these compounds possess weak to medium inhibitory activity against some bacteria and Mycobacterium tuberculosis.

Pyrrolines Fig. 2 β-Lactams and pyrrolo-thiazolones.

Flavor and Fragrance:

A five-membered N-heterocyclic ring compound, 2-acetyl-1-pyrroline (2AP), was identified for the first time as the important aroma component of cooked rice and the volatile oil of freeze-dried pandan leaves. According to the suggestions made by most of the previous reports, 2AP was presumed to be a Maillard reaction product because of its occurrence after boiling or cooking of materials. The isolation methods used in the previous reports were mainly under thermal treatments such as continuous steam distillation and solvent extraction (SDS). And 2AP is promising to be utilized in essence and flavor industry.

Pharmaceutical Chemistry:

Recent evidence indicates a biochemical link between the functioning γ-aminobutyric acid (GABA) system and the symptoms of Huntington's disease, Parkinsonism, and epilepsy. Δ1-Pyrroline, 5-methyl-Δ1-pyrroline, and 5,5-dimethyl-Δ1-pyrroline have been identified as substances metabolized to γ-aminobutyric acid, 4-aminopentanoic acid (methylGABA), and 4-amino-4-methylpen-tanoic acid (dimethylGABA), respectively. An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of Δ1-pyrroline to GABA and its lactam, 2-pyrrolidinone.The present studies suggest that pyrrolines may represent a chemical class of brain-penetrating precursors of pharmacologically active analogues of GABA for the treatment of Huntington's disease, Parkinsonism, and epilepsy diseases.

References

  1. 1-Pyrrolines (3,4-Dihydro-2H-pyrroles) as a Template for New Drugs, Arch. Pharm. Pharm. Med. Chem., 334, 183-188
  2. Identification and Quantitation of the Rice Aroma Compound, 2-Acetyl-1-pyrroline, in Bread Flowers (Vallaris glabra Ktze), J. Agric. Food Chem. 2003, 51, 2, 457-462
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