A Facile Synthesis of Novel Pyrrolidine Dendrimers by Terminal Group Modification through 1,3-Dipolar Cycloaddition Reaction

Abstract

A series of novel dendrimers with pyrrolidine as surface group has been achieved in high yields by terminal-group modification on chalcone dendrimers through the application of 1,3-dipolar cycloaddition reaction. In 1,3-dipolar cycloaddition, azomethine ylides (AMY) with alkenes afforded five-membered N-methyl pyrrolidine. The formation of N-methyl pyrrolidine in the dendritic structure would be an important candidate in the field of biology and pharmacology.Design and synthesis of dendritic architectures have been active areas of research because of their countless applications in the field of biology and material sciences. 1-4 Dendrimers are highly branched, regularly ordered monodisperse three-dimensional architecture. The combination of discrete numbers of functionalities and high local densities of active groups in dendrimers has attracted a lot of attention from those active in medicinal chemistry. 5,6 In this way, introduction of heterocyclic unit into dendritic structure would be an important candidate for medicinal applications.Pyrrolidine, an important nucleus in the five-membered heterocyclic ring systems, is one of the main building blocks for the syntheses of many natural products and pharmaceuticals. 7-12 The 1,3-dipolar cycloaddition reaction of azomethine ylides (AMY) with alkenes is a powerful method for the synthesis of pyrrolidines with high stereoselectivity. 13,14 Pyrrolidine and its derivatives have gained much attention during recent years due to their interesting biological and medicinal properties. Pyrrolidine derivatives find applications as organocatalytic and semiconducting agents. 15-17 Pyrrolidine derivatives play a crucial role in pharmacological applications such as preventing and treating rheumatoid arthritis, asthma, allergies, rhinitis, and related diseases as they inhibit the production of intracellular phospholipase A2 and prostaglandin E2. 18 Furthermore, pyrrolidines are important building blocks in organic synthesis. [19][20][21] Methodology plays a pivotal role for the synthesis of dendrimers in modern chemistry. Recently, cycloaddition reactions are being involved for the synthesis of such dendrimers. 22,23 In this association, 1,3-dipolar cycloaddition is one of the most powerful method to introduce five-membered heterocycles in to the dendritic architectures. 24,25 Recently, our research group has reported the synthesis of novel dendrimers with chalcone and carbohydrate moiety at the surface using 'click' methodology. 26,27 In connection with this, we report herein the synthesis of some novel pyrrolidine dendrimers 1-4 ( Figure 1) through 1,3-dipolar cycloaddition reaction using previously reported chalcone dendrimers 5-8. 28 In order to synthesize the pyrrolidine dendrimer 1, the dendritic chalcone 5 underwent 1,3-dipolar cycloaddition reaction with 3.1 equivalents of sarcosine and 6.0 equivalents of paraformaldehyde in toluene under refluxing condition for 12 hours to give the pyrrolidine dendrimer 1 in 91% yield (Scheme 1). The 1 H NMR spectrum of 1 displayed three s...

An overview on synthetic strategies for the construction of star-shaped molecules

“…Pyrrolidine. Rajakumar et al 85 reported the synthesis of some novel star-shaped molecules with pyrrolidine side arms 78, 80, 82 and 84 in high yields through 1,3-dipolar 86 reported the synthesis of multi-armed thiazole derivatives 88a and 88b in 67 and 69% yields, respectively, by the reaction of tris(aldehyde thiosemicarbazones) 85a and 85b with each of 2-bromo-1-phenyl ethanone 86 and 2-bromo-1-(4chlorophenyl)ethanone 87 in ethanol at reux in the presence of TEA (Scheme 22). The same methodology was extended to the preparation of tetrakis-and hexakis(thiazoles) 90a, 90b, 92a and 92b in good yields from the corresponding poly(aldehyde thiosemicarbazones) 89a, 89b, 91a and 91b (Schemes 23 and 24).…”

“…These observations clearly demonstrate that perturbation of molecular structure has remarkable inuence on their bulk macroscopic properties. 85 4.3.1.1.3.3. 1,3,4-Thiadiazole.…”

Chalcones as Versatile Synthons for the Synthesis of 5- and 6-membered Nitrogen Heterocycles

“…Therefore, the 1,3-dipolar cycloaddition reaction of ninhydrin, L-proline and chalcones provided spiroindane-1,3-dione pyrrolizidines in good yields and with high regio-and stereoselectivity (Scheme 4) [64]. Chalcone dendrimers undergo 1,3-dipolar cycloaddition reaction with sarcosine and an excess of paraformaldehyde in refluxing toluene to prepare Nmethylpyrrolidine dendrimers [65]. Moemeni et al used a one-pot four-component 1,3-dipolar cycloaddition reaction of ninhydrin, arylenediamines, sarcosine and chalcones to prepare highly substituted pyrrolidines in good yields and stereoselectivity (Scheme 5) [66].…”

Synthesis and photophysical studies on triazole bridged dendrimers with phenothiazine as a surface unit

“…Recently, we have reported the synthesis of dendrimer with dimethyl isophthalate, 14 pyrrolidine, 15 quinoline, 16 and pyreno-chalcone 17 as surface groups with 1,2,3-triazole as…”