[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-228342-en":3,"doc-seo-228342-105":30,"detail-sidebar-cat-0-en-105":92},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},228342,1374402524268,"Berry Peter","https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2",8,"Research & Report","Polyketopiperazines: triketopiperazines, tetraketopiperazines synthesis, reactions, bioactivities and applications","Several polyketopiperazines represent the simplest heterocyclic compounds found in nature, acting as a vital base-structure for many bioactive compounds. They are widely distributed in microorganisms, food, and beverages with diverse bioactivities, such as antiviral, anticancer, antioxidant, and neuroprotective properties. Focusing on triketopiperazines and tetraketopiperazines, triketopiperazines provide valuable molecular scaffolds for synthetic biology, while tetraketopiperazines support economically beneficial chemical engineering. Their extra-rigid conformations resist enzymatic degradation, enabling therapeutic motif and sustainable energy storage.","A Platinum Open Access Journal for Organic Chemistry  \nReview  \nFree to Authors and Readers DOAJ Seal Arkivoc 2022, part i, 221-261  \nPolyketopiperazines: triketopiperazines, tetraketopiperazines synthesis,  \nreactions, bioactivities and applications  \nNabaweya Abdelsalem Sharafeldin  \nDepartment of Pharmaceutical Chemistry, Tanta University, El Giesh street, 3111, Tanta, Egypt  \n[Email:](Email: nabawia.eldeen@pharm.tanta.edu.eg)[ ](Email: nabawia.eldeen@pharm.tanta.edu.eg)[nabawia.eldeen@pharm.tanta.edu.eg](Email: nabawia.eldeen@pharm.tanta.edu.eg)  \nReceived 02-02-2022 Accepted 03-23-2022 Published on line 05-12-2022  \nAbstract  \nSeveral polyketopiperazines represent the simplest heterocyclic compounds found in nature, acting as a vital base-structure for many bioactive compounds. They are widely distributed in microorganisms, food, and beverages with diverse bioactivities, such as antiviral, anticancer, antioxidant, and neuroprotective properties. Focusing on triketopiperazines and tetraketopiperazines; triketopiperazines possess important biological properties and used for production of the valuable molecular scaffolds in synthetic biology, whereas tetraketopiperazines are economically beneficial for chemical engineering. Noteworthy, they have extra-rigid conformations and are more resistant to degradation by enzymes. Therefore, they represent an interesting subclass of heterocycles with high potential to be used in the production of new effective therapeutic motif and sustainable energy storage structures.  \nKeywords: Polyketopiperazines; triketopiperazines; tetraketopiperazines; synthesis; reactions; bioactivities; applications  \nTable of Contents  \n1. Introduction  \n2. Piperazinones (2-Oxypiperazines, 2-Ketopiperazines)  \n3. Diketopiperazines (Cyclo-Peptides, cyclo[Gly-Gly)  \n4. Triketopiperazines  \n4. 1. Historical background  \n4. 2. Synthesis of 2,3,5-triketopiperazines  \n4. 2. 1. Via the reaction of oxalic acid derivatives with amino acid amid  \n4. 2. 2. via amino amide with oxalyl diimidazole or oxalyl 1,1’-dibenzotriazole  \n4. 2. 3. Conversion of DKP derivatives into TKP derivatives  \n4. 3. Reaction  \n4. 3. 1. The formation of C–C bonds  \n4. 3. 1. 1. Acylation of triketopiperazines  \n4. 3. 1. 2. Michael-addition reactions  \n4. 3. 2. Reduction of the C-3 position  \n4. 3. 3. Rearrangement of TKP to bicyclo[2 .2. 2]diazaoctane  \n4. 3. 4. Rearrangement of TKP to diazabicyclo- [2 .2. 1]heptane  \n4. 3. 5. Reaction with Grignard reagent  \n4. 3. 6. Aldol condensation  \n4. 4. Bioactivity of TKP derivatives and applications  \n5. Tetraketopiperazines  \n5. 1. Synthesis  \n5. 2. Reaction  \n5. 2. 1. Salt formation  \n5. 2. 2. Hydrazone formation  \n5. 2. 3. Reduction  \n5.3. Applications and uses  \n6. Conclusions  \n7. Abbreviations  \n8. References  \n1. Introduction  \nNitrogen containing heterocycles have a vital role in life sciences, because they occur in many natural products, such as vitamins, hormones, antibiotics as well as in numerous approved and marketed medicines.1-6 Further, the N-heterocycles are considerably used as a building blocks for a number of medications, owing to the ability of the nitrogen atom to form hydrogen bonding with biological receptors.7-11 In addition, several nitrogencontaining heterocycles are well known to have a broad array of bioactivities.12-18 Hence, these compounds have always been desirable objectives to synthetic organic chemists and researchers.  \nMost importantly, piperazine is an essential heterocyclic motif in many biologically active compounds with various pharmacological activities.19-27 For example, clozapine 1 is strongly sedative and has muscle-relaxant  \nproperties, amoxapine 2 has antidepressant activity, trimetazidine 3 is an antischemic agent and cyclizine 4 is used to treat nausea and vomiting28,29 (Figure 1) .  \nFigure 1. Structures of some piperazine-based drugs.  \nStructurally, piperazine has a six-membered saturated ring with two nitrogen atoms at 1-and 4-positions. This fea","cbCaikxz6Jtkl4RM","https://ap.wps.com/l/cbCaikxz6Jtkl4RM","pdf",1350227,1,41,"English","en",105,"# Introduction\n# Piperazinones (2-Oxypiperazines, 2-Ketopiperazines)\n# Diketopiperazines (Cyclo-Peptides, cyclo[Gly-Gly)\n# Triketopiperazines\n## Historical background\n## Synthesis of 2,3,5-triketopiperazines\n## Reaction\n## Bioactivity of TKP derivatives and applications\n# Tetraketopiperazines\n## Synthesis\n## Reaction\n## Applications and uses\n# Conclusions\n# Abbreviations\n# References","[{\"question\":\"What biological roles do polyketopiperazines play?\",\"answer\":\"Polyketopiperazines serve as base structures for many bioactive compounds and are associated with diverse activities such as antiviral, anticancer, antioxidant, and neuroprotective effects.\"},{\"question\":\"How do triketopiperazines and tetraketopiperazines differ in application focus?\",\"answer\":\"Triketopiperazines are highlighted for producing valuable molecular scaffolds for synthetic biology, whereas tetraketopiperazines are emphasized as economically beneficial for chemical engineering.\"},{\"question\":\"Why are polyketopiperazines considered promising for therapeutic and energy-storage applications?\",\"answer\":\"Their extra-rigid conformations make them more resistant to enzymatic degradation, supporting use in generating new effective therapeutic motifs and sustainable energy storage structures.\"}]","Polyketopiperazines: triketopiperazines, tetraketopiperazines synthesis, reactions, bioactivities and applications | 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biological roles do polyketopiperazines play?","Question",{"text":76,"@type":77},"Polyketopiperazines serve as base structures for many bioactive compounds and are associated with diverse activities such as antiviral, anticancer, antioxidant, and neuroprotective effects.","Answer",{"name":79,"@type":74,"acceptedAnswer":80},"How do triketopiperazines and tetraketopiperazines differ in application focus?",{"text":81,"@type":77},"Triketopiperazines are highlighted for producing valuable molecular scaffolds for synthetic biology, whereas tetraketopiperazines are emphasized as economically beneficial for chemical engineering.",{"name":83,"@type":74,"acceptedAnswer":84},"Why are polyketopiperazines considered promising for therapeutic and energy-storage applications?",{"text":85,"@type":77},"Their extra-rigid conformations make them more resistant to enzymatic degradation, supporting use in generating new effective therapeutic motifs and sustainable energy storage 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