1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents

Abstract

In the present perspective it is described the advances and real possibilities of 1,3-dipolar cycloadditions as key step in the total synthesis of virus inhibitors. Azides, nitrones, and azomethine ylides are the most appropriate 1,3-dipoles for the synthesis of privileged structures 10 with the highest biological response against viruses.

Coinage metal complexes as chiral catalysts for 1,3-dipolar cycloadditions

“…Such as it has been reported in previous works by our group, molecule 22 is the key intermediate in the elaboration of 2 nd generation GSK inhibitors of the virus causing hepatitis C of the type 23 [55]. When AgClO 4 , AgSbF 6 , and AgTfa were tested, unexpectedly, the reactions afforded good chemical yields at 25 ºC, for 48 h and with high enantioselections, especially for the reaction carried out with silver perchlorate (88% ee) [50].…”

Enantioselective synthesis of proline derivatives by 1,3-dipolar cycloadditions

“…16 (−)-α-Kainic acid 3, (−)-domoic acid 4, and acromelic acid 5 belong to a 17 family of kainoid natural neurotoxins, promoting a potent stimulation of 18 the central nervous system, brain damage, and neurological disorders, 19 respectively (Chart 1) [1]. In addition, synthetic molecules 6-9 have been 20 identified as potent hepatitis C virus (HCV) inhibitors blocking the viral 21 RNA-dependent RNA-polymerase [6]. The last proline 9 (GSK 625433), 1 which is now in phase I trials, has shown potent selective activity against 2 type 1a and 1b HCV polymerases (D. Haigh, GlaxoSmithKline, UK).…”

“…In recent years, 18 azomethine ylides have become one of the most investigated classes of 1, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] dipoles due to their cycloaddition chemistry [9,10]. 20 The high reactivity of the azomethine ylides requires their generation 1 in situ, which can be achieved through several routes.…”

Dual chiral silver catalyst in the synthetic approach to the core of hepatitis C virus inhibitor GSK 625433 using enantioselective 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes

“…However, the development of antiviral compounds (commercially available or in clinical survey) constitutes one of the main applications of these skeletons. 2,3 At this moment, many antiviral agents (used individually or in combination with another drugs) administrated to patients include a nitrogenated five-membered ring, for example, elbasvir, grazoprevir, velpatasvir, ombitasvir, paritaprevir, boceprevir, telaprevir and daclatasvir have been recently developed. 4 The complex skeleton of these molecules contrast with a family of prolinate derivatives 1-3 ( Figure 1) reported by GSK through successive evolutions.…”