The Synthetic Routes of 4-Ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

Sure, here is an article about the synthetic routes of 4-ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, a naturally occurring compound that has been studied for its potential pharmaceutical applications.

Introduction:

4-Ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, also known as isoliquiritigenin, is a naturally occurring compound that has been studied for its potential pharmaceutical applications.
It has been found to have anti-inflammatory, anti-allergic, and anti-tumor properties, among others.
The compound is extracted from the plant Liquidambar orientalis, which is commonly found in Asia and Australia.

Synthetic routes:

There are several synthetic routes that have been reported in the literature for the synthesis of isoliquiritigenin.
Here are some of the most commonly used methods:

1. The Koga synthesis: This is one of the earliest reported synthesis methods for isoliquiritigenin.
   In this method, 2,6-dimethylaniline is nitrated to form 2,6-dimethyl-4-nitroaniline, which is then reduced to form 2,6-dimethyl-4-aminoaniline.
   This substance is then coupled with 3-ethyl-2-oxo-1,3-oxazolidin-3-one to form the isoliquiritigenin.
   
2. The Suzuki coupling method: This method involves the coupling of 4-ethyl-3-hydroxyl-2-oxo-1,3-oxazolidin-3-one with phenylboronic acid to form the isoliquiritigenin.
   
3. The Py-MIDA method: This method involves the use of PyBOP (pyrrolidine-2,6-dione-based Biginelli reaction) and MIDA (methoxy-7-azabenzotriazole-based condensation) reagents to synthesize the isoliquiritigenin.
   
4. The Ullmann condensation method: This method involves the condensation of 3-ethyl-2-oxo-1,3-oxazolidin-3-one with phenyl acetate to form the isoliquiritigenin.
   

Advantages and limitations of synthetic routes:

Each of the above synthetic methods has its own advantages and limitations.
For example, the Koga synthesis is relatively simple and efficient, but it requires the use of toxic reagents such as nitric acid.
The Suzuki coupling method is more efficient and cleaner, but it requires the use of costly reagents and specialized equipment.
The Py-MIDA method is also relatively efficient, but it requires the use of multiple reagents.
The Ullmann condensation method is relatively simple and efficient, but it requires the use of a silica gel column to purify the product.

Conclusion:

Isoliquiritigenin is a naturally occurring compound that has been studied for its potential pharmaceutical applications.
There are several synthetic routes that have been reported in the literature for the synthesis of isoliquiritigenin, each with its own advantages and limitations.
The choice of synthetic route will depend on various factors such as cost, efficiency, and availability of reagents.
As research continues, new synthetic routes may be developed that offer improved efficiency and purity, making it easier to obtain this compound for further study and application.