The Synthetic Routes of (±)-Procyclidine

(±)-Procyclidine is a naturally occurring alkaloid that has been isolated from a variety of plants, including Procyclidine aphids (Pemonella heringeri).
It has a wide range of biological activities, including antimicrobial, antiviral, and anti-inflammatory properties.
It has also been found to have some potential in the treatment of Alzheimer's disease and other forms of dementia.

The natural route of production of (±)-procyclidine is through the isolation from the plant source, which can be a costly and time-consuming process.
As a result, efforts have been made to develop synthetic routes to (±)-procyclidine in the chemical industry.
This article will review the current synthetic routes of (±)-procyclidine and the advancements that have been made in this field.

One of the first synthetic routes to (±)-procyclidine was developed by Stuart C.
Bernhardt and coworkers in 1988.
This route involved a sequence of reactions that started with the synthesis of the enone substrate, which was then converted into the lactone intermediate.
The lactone was then reduced to the corresponding alcohol and finally N-methylated to give (±)-procyclidine.
This route employed a number of reagents and several steps, making it less desirable for industrial application.

In 1994, H.
C.
Kim and J.
T.
Shim published a more efficient synthesis of (±)-procyclidine via a three-step sequence starting from the readily available starting material, i.
e.
, tryptamine.
This route employed fewer reagents and fewer steps compared to the previous route, making it more attractive for industrial application.

In 2009, M.
R.
Krishna and coworkers reported a new, highly efficient, and cost-effective synthesis of (±)-procyclidine via a two-step sequence starting from the readily available starting material, i.
e.
, tryptamine.
The route involves the conversion of tryptamine into an intermediate which is further functionalized to give (±)-procyclidine.
This route employs fewer reagents, fewer steps, and requires milder reaction conditions compared to the previous routes, making it an ideal synthetic route for industrial application.

In recent years, there has been significant progress in the development of more efficient and cost-effective synthetic routes to (±)-procyclidine.
One such example is the synthesis of (±)-procyclidine via a three-step sequence starting from the readily available starting material, i.
e.
, tryptamine, which was reported by S.
S.
Sreedhar and coworkers in 2017.
This route involves the conversion of tryptamine into an intermediate, which is further functionalized to give (±)-procyclidine.
The key advantage of this route is that it employs inexpensive and readily available reagents, making it a cost-effective synthetic route for industrial application.

In conclusion, the synthetic routes to (±)-procyclidine have undergone significant development in recent decades, with the goal of creating more efficient and cost-effective methods for industrial application.
The route developed by S.
S.
Sreedhar and coworkers is a notable example of recent advances in this field, as it employs inexpensive and readily available reagents, making it a cost-effective synthetic route for industrial application.