Reductive Aldol‐type Reactions in the Synthesis of Pharmaceuticals

Abstract

The efficient chemo-, regio-and stereoselective formation of saturated carbon-carbon fragment is the critical challenge of organic synthesis; therefore, developing new methods for formation of these bonds is paramount. The rising interest for reductive aldol-type reactions is conditioned by its versatile applications, allowing the efficient formation of carbon-carbon bonds. The review aims to highlight the advantages and disadvantage of reductive aldol-type reactions to total synthesis of pharmaceutical substances in order to summarize knowledge and encourage further investigation of the field.

Complete Computational Reaction Mechanism for Foldamer-Catalyzed Aldol Condensation

“…In nature, the retro-aldol (reverse direction, CC-breaking) reaction is involved in metabolic pathways, such as those for amino acids and carbohydrates. 1 It is a prevalent chemical transformation 2 employed, for example, in the synthesis of pharmaceuticals 3,4 and biofuels. 5−7 Many catalysts exist for aldol reactions under varied conditions and can range from simple amines to biologics (Figure 1).…”

The assembly of integrated continuous flow platform for on-demand rosiglitazone and pioglitazone synthesis

“…8 Over the past few decades, various batch process techniques have been developed for the synthesis of thiazolidinediones. [17][18][19][20][21][22] In 2003, Li et al suggested a polymer-assisted multi-step (7 steps) synthetic route for the synthesis of thiazolidinediones; however, it suffered from longer production time (9-10 days) and poor overall yield (44%). 22 To reduce the reaction time, Gaonkar et al developed a microwave-assisted synthesis, which afforded the compound of interest in 250 min (Scheme 1b).…”

“…25 So far, most of the reported protocols have used only the batch process NKH-platform with different base and solvent systems for the synthesis of thiazolidinediones and their related intermediates. [17][18][19][20][21][22] Thiazolidinedione intermediate synthesis is typically carried out at different locations. Transporting an intermediate to another place not only increases the time, but also generates huge pollution and results in higher manufacturing costs (rosiglitazone 11 000-25 000$ per kg).…”

“…amount of the 2 (2-(methylamino)ethanol) (comparative Table S1 †). 19,20,22,23 After optimizing the kilogram scale integrated continuous flow process for the synthesis of rosiglitazone intermediate 3, we examined the continuous flow nucleophilic substitution reaction (N-platform) as an individual step between compounds 3 and 4. Firstly, we prepared the stock solution of compound 3 (0.25 M) in DMF and compound 4 (0.25 M) in DMF, which were charged in two separate syringes and were introduced to the T-junction (T 1 ) for mixing.…”

Easy Route to New Fused Dihydroisoquinoline-Naphthyridinone Frameworks

“…The pyrido[2,1-a]isoquinoline ring system is an important heterocyclic scaffold that occurs in the alkaloids emetine, [1][2][3] tetrabenazine, 4,5 schulzeines A, B, C 1a-c, [6][7][8] isoalangioside. 9,10 The synthetic benzo[a]chinolizinone (Ro 41-3696) is used as an effective non-sedative hypnotic for the induction and maintenance of sleep.…”