Practical Total Synthesis of the Anti-Influenza Drug GS-4104

Application of Heterogeneous Catalysts in the First Steps of the Oseltamivir Synthesis

“…For the moment, the most scalable route to oseltamivir involves (−)-quinic acid as the starting material (Scheme 1), as it shares a good number of steps with the well-known shikimic acid route. The first step of the oseltamivir syntheses, starting from (−)-quinic acid (1) [18,19], consists of the acetalization of the two cis hydroxyl groups in positions 3 and 4 with acetone, with concomitant lactonization of the carboxylic group and the cis hydroxyl at carbon 5, catalyzed by p-toluenesulfonic acid, leading to the acetal-lactone (2a) (Scheme 2). The lactone ring is then opened by a reaction with EtONa/EtOH, to obtain the acetal-ester (3ab).…”

Synthesis and biological evaluation of shikimic acid derivatives

“…Shikimic acid is well known as starting material for production of oseltamivir phosphate (Tamiflu), an active neuraminidase inhibitor [1][2][3][4][5]. Although of some reports on total oseltamivir synthesis from other sources, shikimic acid remains the principal starting material for making oseltamivir.…”

Discovery of Quinic Acid Derivatives as Oral Anti-inflammatory Agents

“…96,115,121 The synthesis of the lactone 14 was carried out using quinic acid 1 and PTSA in refluxing 2,2-DMP and acetone.The synthesis of compound 26 was carried out in two steps, first using sinapic acid 21 treated with Ac 2 O in pyridine, DMAP, at room temperature; then the product was refluxed in SOCl 2 and CH 2 Cl 2 . Compounds 14 and 26 were mixed in CH 2 Cl 2 , treated with DMAP, Pyridine, at room temperature, and then resulting ester 27.…”

“…96,115,121 The synthesis of the lactone 14 was carried out using quinic acid 1 and PTSA in refluxing 2,2-DMP and acetone. lactone 14 was allowed to react with N-propyl amine with acetic acid at 85C, and then resulting ester 15; The synthesis of compound 31 was carried out in two steps, first using caffeic acid 30 treated with Ac 2 O in pyridine, DMAP, at room temperature; then the product was refluxed in SOCl 2 and CH 2 Cl 2 .…”

“…The basic idea is to make intermediates less polar, so aqueous wash and separation are possible during compound purification. In Scheme 2-2, intermediate 14 was obtained in one step with high yield (>80%), 115 it can be purified just by liquid-liquid separation followed by crystallization.…”