The Synthetic Routes of Granisetron

Granisetron is a potent and specific antagonist of the 5-hydroxytryptamine (5-HT3) receptor, which is involved in the emesis response to chemotherapy.
It is widely used in the treatment of nausea and vomiting in cancer patients undergoing chemotherapy.
The synthesis of granisetron has undergone various improvements over the years, leading to the development of more efficient and cost-effective synthetic routes.

Early synthetic routes of granisetron involved the use of complex synthetic methods that required many steps and hazardous reagents.
However, with advancements in organic synthesis, more efficient and environmentally friendly methods have been developed.
The most commonly used synthetic routes for granisetron can be broadly classified into three categories: the PAS-mediated method, the N-BOC-protected method, and the hydrogenation method.

The PAS-mediated method involves the use of para-toluenesulfonyl chloride (PAS) as a reagent to introduce a tosylate group into the indole ring of granisetron.
This group is then protected with a tert-butyldimethylsilyl (TBDMS) group to prevent its reaction with amines.
The TBDMS group is then removed under acidic conditions, and the resulting amine is converted into the desired compound using standard synthetic methods.
The PAS-mediated method is considered to be one of the most efficient synthetic routes for granisetron, as it provides high yields and a high level of stereochemical control.

The N-BOC-protected method involves the use of N-bromoacetamide (N-BOC-Br) as a reagent to introduce a BOC group into the amine nitrogen of granisetron.
The BOC group is then protected with a TBDMS group, and the TBDMS group is removed under acidic conditions to give the desired compound.
This method is less severely reactive than the PAS-mediated method and can be used with less reactive amines.

The hydrogenation method involves the reduction of the nitrile group of granisetron to an amine using hydrogen gas in the presence of a catalyst.
This method is less expensive than the other methods and does not require the use of hazardous reagents.
However, it is less efficient than the other methods and typically results in lower yields.

Overall, the choice of synthetic route for granisetron depends on several factors, including the availability of reagents and equipment, the desired yield and stereochemical control, and the environmental impact of the synthesis.
As the field of organic synthesis continues to advance, it is expected that more efficient and environmentally friendly methods for the synthesis of granisetron will be developed.