Recent advances in the synthetic chemistry of 1,5‐benzothiazepines: A minireview

Abstract

Benzothiazepine, a prominent “drug prejudice core”, is a heterocyclic moiety of immense importance due to its presence in a wide range of bioactive compounds. They act as a primary “biolinker” in diverse synthetic routes to obtain bioactive molecules and serve as important templates in synthetic and medicinal chemistry. They are known to possess a plethora of pharmacological activities, which include Ca2+ channel blockers, CNS acting agents, anti‐HIV, ACE inhibitors, antimicrobial, antifungal, anticancer. Their promising behaviour as drug molecules led the scientific community to develop novel, mild, green, and highly efficient synthetic routes for their synthesis. The conventional synthesis generally involved the condensation of chalcones with 2‐aminothiophenol in the presence of acid/base with high‐temperature heating, mostly resulting in poor yields or mixtures. However, recent trends are replacing these conditions with mild and green conditions through organocatalysis or other methodologies. In this review, an attempt has been made by authors to summarize (a) Recent developments in the synthetic strategies of 1,5‐benzoathiazepines and its derivatives (b) Conventional methods for the synthesis of 1,5‐benzothiazepines including progress in the green chemistry routes (c) Applications of various metals and organocatalysts to achieve the enantioselective synthesis of title compounds.

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

“…288 However, not much Various synthetic methods have been developed to procure thiazepines and benzothiazepines over the past years and new approaches continue to emerge, owing to their importance as intermediates for synthesizing various biologically important derivatives. 291,292 These molecules have found their place as anticancer candidates and are being developed by various organic and medicinal chemists to aid to the future field of cancer chemotherapy. 293,294 Also, various tricyclic antidepressants like clomipramine has also shown to display antitumor profile in a study carried out by Palmerton et al 295 Hence, various thiazepines and benzothiazepines can aid to the future field of cancer chemotherapeutics.…”

“…Tianeptine, diltiazem, clomipramine, and quetiapine which are tricyclic azepines have already been in lime‐light for their as anti‐psychotics 290 . Various synthetic methods have been developed to procure thiazepines and benzothiazepines over the past years and new approaches continue to emerge, owing to their importance as intermediates for synthesizing various biologically important derivatives 291,292 . These molecules have found their place as anticancer candidates and are being developed by various organic and medicinal chemists to aid to the future field of cancer chemotherapy 293,294 .…”

Visible Light as the Key for the Formation of Carbon–Sulfur Bonds in Sulfones, Thioethers, and Sulfonamides: An Update

“…When other alkenes were used, β-ketosulfones (10 examples, 45-75%) were obtained. 72 The reaction is not selective because the product deriving from the addition of iodine is always recovered. A mechanism hypothesis is illustrated.…”

Dibenzothiazepine Based MCR Chemistry

“…[20] Although there are quite a few sequential approaches towards 1,5-dibenzodiazepine derivatives, divergent approaches which allow the rapid synthesis of versatile libraries for screening docks are scarce. [2,3,21,22] Multicomponent reactions chemistry (MCRs) [23] is one of the tools that allows for fast and convergent access on polycyclic (more than three rings), diverse www.eurjoc.org and complex adducts. [24][25][26][27][28] In general, MCRs have been utilized towards the 1,5-dibenzothiazepine core, e. g. Ugi-Joullie threecomponent reaction (UJ-3CR), [29] Mannich, [30] Strecker, [31] Pudovik reaction [32] and aza-Henry.…”

“…As a continuation of the quest for exploring different areas of the chemical space [1] for novel entities with interesting dynamic properties, we spot the 1,5‐dibenzothiazepine (Figure 1A). It constitutes a privileged scaffold with unique properties and conformations (Figure 1B) [2,3] . Three features of the dibenzothiazepine scaffold renders it a prime hub for further elaboration and medicinal chemistry strategic syntheses: a secondary amine, an oxidizable sulfur atom embedded in a tricyclic ring system and a unique “butterfly” conformation (Figure 1A, Figure 1B) [4,5] .…”