Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
558
Citations
1.1m
Views
723
Articles
Volume 8 Number 1 2024
RESEARCH ARTICLE (Open Access)
Innovative Piperidine-Catalyzation in Protecting Carbonyl Compounds with Implications for Angiogenesis and Inflammation
Mukhlif Mohsin Slaihim 1*, Luay Ali Dhahi 1, Abeer Hussein Ali 1
Journal of Angiotherapy 8 (1) 1-15 https://doi.org/10.25163/angiotherapy.819343
Submitted: 21 August 2023 Revised: 11 December 2023 Published: 17 January 2024
Abstract
Introduction: This study explores the application of piperidine-catalyzed protection, an innovative technique, for safeguarding various carbonyl compounds functioning as acetals in a generic reaction. Specifically, we investigate the catalysis of 2-amino-1,3-propanediol-2-methyl with various aromatic aldehydes, leading to the production of cis and trans-5-methyl-2-(mono or di-substitutions-phenyl)-1,3-dioxane-5-amine. Methods: Identification of all newly formed products is achieved through the utilization of spectroscopic techniques, including IR, 1H-NMR, and 13C-NMR spectroscopy. Molecular interactions and potential therapeutic applications of compounds E1 and E2 are demonstrated with cAMP-specific phosphodiesterase (1zkl) and oxidized purine nucleoside triphosphate hydrolase (5ws7). Detailed structural analyses highlight specific hydrogen bonds, pi-pi stacked interactions, and alkyl contacts formed by these compounds with target proteins. A comprehensive bioinformatics approach involves GO enrichment, STRING protein-protein association networks, KEGG pathway analysis, and Reactome pathways to elucidate biological processes, molecular functions, and cellular components associated with the compounds. Results: Compounds E1 and E2 exhibit diverse enrichment profiles, suggesting their involvement in various signaling cascades, neurotransmission, immune responses, and cancer pathways. Comparative analysis of five compound pairs (A1/A2, B1/B2, C1/C2, D1/D2, E1/E2) reveals subtle distinctions in enrichment patterns, implying unique pharmacological advantages for each pair. Conclusion: This study introduces a separate investigation on piperidine-catalyzed protection of carbonyl groups in aldehydes, presenting a practical approach. Emphasizing the significance of understanding distinct biological signatures, our findings guide therapeutic applications and compound optimization, particularly in the context of anti-cancer therapeutics. The compounds show potential in modulating neuronal function, neurotransmission, cancer mechanisms, and immune responses, suggesting promising avenues for future research and development.
Keywords: Carbonyl protection, 1,3-propanediol, 5-methyl-2-(sub-phenyl)-1,3-dioxane-5-amine.
References
14 Duan C, Yu M, Xu J, Li BY, Zhao Y, Kankala RK. Overcoming Cancer Multi-drug Resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges. Biomedicine & Pharmacotherapy. 2023 Jun 1;162:114643.
15 Schmidt M, Ungvári J, Glöde J, Dobner B, Langner A. New 1, 3-dioxolane and 1, 3-dioxane derivatives as effective modulators to overcome multidrug resistance. Bioorganic & medicinal chemistry. 2007 Mar 15;15(6):2283-97.
24.Alshehade SA, Al Zarzour RH, Murugaiyah V, Lim SY, El-Refae HG, Alshawsh MA. Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches. Saudi Pharmaceutical Journal. 2022 Nov 1;30(11):1572-88.. https://doi.org/10.1016/j.jsps.2022.09.001
Arafath MA, Adam F, Al-Suede FS, Razali MR, Ahamed MB, Majid AM, Hassan MZ, Osman H, Abubakar S. Synthesis, characterization, X-ray crystal structures of heterocyclic Schiff base compounds and in vitro cholinesterase inhibition and anticancer activity. Journal of Molecular Structure. 2017 Dec 5;1149:216-28.
Banik BK, Chapa M, Marquez J, Cardona M. A remarkable iodine-catalyzed protection of carbonyl compounds. Tetrahedron letters. 2005 Mar 28;46(13):2341-3.
Beregszászi T, Molnár Á. Microwave-assisted acetalization of carbonyl compounds catalyzed by reusable envirocat® supported reagents. Synthetic communications. 1997 Nov 1;27(21):3705-
Boukachabia M, Bendjeffal H, Aribi-Zouioueche L, Riant O, Bouhedja Y. Chemoselective Synthesis of Acyclic Acetals by Natural Kaolin under Green Chemistry Conditions. ChemistrySelect. 2022 Jun 13;7(22):e202104610.
Clerici A, Pastori N, Porta O. Mild acetalisation of mono and dicarbonyl compounds catalysed by titanium tetrachloride. Facile synthesis of β-keto enol ethers. Tetrahedron. 2001 Jan 1;57(1):217-25.
Corma A, Garcia H. Lewis acids: from conventional homogeneous to green homogeneous and heterogeneous catalysis. Chemical Reviews. 2003 Nov 12;103(11):4307-66.
Eid EE, Alshehade SA, Almiman AA, Kamran S, Lee VS, Alshawsh MA. Enhancing the Anti-Leukemic Potential of Thymoquinone-SBE-β-CD Inclusion Complex.. https://doi.org/10.3390/biomedicines11071891
Haque RA, Iqbal MA, Asekunowo P, Majid AA, Khadeer Ahamed MB, Umar MI, Al-Rawi SS, Al-Suede FS. Synthesis, structure, anticancer, and antioxidant activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag (I) N-heterocyclic carbene complexes (Part-II). Medicinal Chemistry Research. 2013 Oct;22:4663-76.
Karimi B, Seradj H, Ebrahimian GR. N-Bromosuccinimide (NBS) as a powerful and chemoselective catalyst for acetalization of carbonyl compounds under almost neutral reaction conditions. Synlett. 1999 Sep;1999(09):1456-8.
Khairuddean M, Slaihim MM, Alidmat MM, Al-Suede FS, Ahamed MB, Shah AM, Majid A. SYNTHESIS, CHARACTERISATION OF SOME NEW SCHIFF BASE FOR THE PIPERIDINIUM 4-AMINO-5-SUBSTITUTED-4H-1, 2, 4-TRIAZOLE-3-THIOLATE, AND THEIR IN-VITRO ANTICANCER ACTIVITIES. Int. J. Natural Sci. Human Sciences.. 2020;1(1):48-58.
Krompiec S, Penkala M, Szczubialka K, Kowalska E. Transition metal compounds and complexes as catalysts in synthesis of acetals and orthoesters: Theoretical, mechanistic and practical aspects. Coordination Chemistry Reviews. 2012 Sep 1;256(17-18):2057-95.
Kshirsagar SW, Patil NR, Samant SD. Chemoselective Protection of Aldehydes in the Presence of Ketones Using RuPVP Complex as a Heterogeneous Catalyst. Synthetic Communications®. 2010 Jan 14;40(3):407-13.
Mahrwald R. A Simple Procedure for the Catalytic Acetalization of Aldehydes. Journal für Praktische Chemie/Chemiker-Zeitung. 1994;336(4):361-2.
Marucci G, Angeli P, Brasili L, Buccioni M, Giardinà D, Gulini U, Piergentili A, Sagratini G, Franchini S. Synthesis and antimuscarinic activity of derivatives of 2-substituted-1, 3-dioxolanes. Medicinal Chemistry Research. 2005 Sep;14:309-31..
Memon AH, Ismail Z, Al-Suede FS, Aisha AF, Hamil MS, Saeed MA, Laghari M, Majid AM. Isolation, characterization, crystal structure elucidation of two flavanones and simultaneous RP-HPLC determination of five major compounds from Syzygium campanulatum Korth. Molecules. 2015 Aug 4;20(8):14212-33.
Ott J, Tombo GR, Schmid B, Venanzi LM, Wang G, Ward TR. A versatile rhodium catalyst for acetalization reactions under mild conditions. Tetrahedron letters. 1989 Jan 1;30(45):6151-4.
Pério B, Dozias MJ, Hamelin J. Solvent free protection of carbonyl group under microwave irradiation. Tetrahedron letters. 1997 Nov 10;38(45):7867-70.
Slaihim MM, Al-Suede FS, Khairuddean M, Ahamed MB, Majid AM. Synthesis, characterisation of new derivatives with mono ring system of 1, 2, 4-triazole scaffold and their anticancer activities. Journal of Molecular Structure. 2019 Nov 15;1196:78-87.
Slaihim MM, Al-Suede FS, Khairuddean M, Sultan SB, Nazari M, Ahamed MB, Majid AM. Antitumor activity and synthesis of new derivatives with fused ring system of 1, 2, 4-triazole scaffold and their characterization. Journal of Molecular Structure. 2023 Oct 5;1289:135834.
Torok DS, Figueroa JJ, Scott WJ. 1, 3-Dioxolane formation via Lewis acid-catalyzed reaction of ketones with oxiranes. The Journal of Organic Chemistry. 1993 Dec;58(25):7274-6.
Wong JC, Sternson SM, Louca JB, Hong R, Schreiber SL. Modular synthesis and preliminary biological evaluation of stereochemically diverse 1, 3-dioxanes. Chemistry & biology. 2004 Sep 1;11(9):1279-91.
Zeng L, Xu G, Gao P, Zhang M, Li H, Zhang J. Design, synthesis and evaluation of a novel class of glucosamine mimetic peptides containing 1, 3-dioxane. European Journal of Medicinal Chemistry. 2015 Mar 26;93:109-20.
29
Save
Save
0
Citation
Citation
1642
View
View
2
Share
Share