The first large scale synthesis of rac-PZQ was developed by the Merck KG and Bayer AG (Merck process).[1,2] Isoquinoline as a cheap starting material was transformed by the Reissert reaction with cyanide and cyclohexanoyl chloride 2 to the cyano amide 3.
I've been working on the sulfur melt reaction, trying to optimize the reaction yield of the singly dehydrogenated product (DHP below). Many studies have been conducted, and here I'll discuss some of what I've found out.
Proton NMR assignment for PZQ has been carried out twice in the literature. Once in a review article: Analytical Profiles of Drug Substances and Excipients, 1998, 25, 463, and once in Arch. Pharm. (Weinheim), 1989, 322, 795-799. Of interest are the large differences in chemical shift between the diastereotopic protons on positions 1 and 6. Need image capture from the pdfs posted below...
The synthesis of rac-PZQ via the Pictet-Spengler route was developed by the Korean Shin Poong Pharmaceutical Company and obtains very low production costs of US¢7 per 600 mg tablet of the drug.
Project A: Development of a low-cost enantioselective synthesis of PZQ. It's an open project, like everything on TSL. Meaning?: contributors can change anything they wish on these pages. If you wish to contribute: please don't leave comments here. Instead, edit the pages below directly or leave comments.
For an inexpensive route to rac-PZQ (and potentially the enantioenriched material), the relevant starting materials (below) are required. While prices may be obtained for these from commercial catalogues, we require realistic prices of these materials on a large (ton) scale to assess whether this approach to PZQ is economically viable. The starting materials are:
