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Coffee, tea, and some other beverages are a major source of caffeine in the human diet. Caffeine can be extracted from tea or coffee using hot water with dichloromethane or chloroform and the leftover is known as decaffeinated coffee or tea. Caffeine and its derivatives were synthesized\n                    <jats:italic>via<\/jats:italic>\n                    different procedures on small and large scales. It competitively antagonizes the adenosine receptors (ARs), which are G protein\u2010coupled receptors largely distributed in the human body, including the heart, vessels, brain, and kidneys. Recently, many reports showed the effect of caffeine derivatives in the treatment of many diseases such as Alzheimer's, asthma, parkinsonism, and cancer. Also, it is used as an antioxidant, anti\u2010inflammatory, analgesic, and hypocholesterolemic agent. The present review article discusses the synthesis, reactivity, and biological and pharmacological properties of caffeine and its derivatives. The biosynthesis and biotransformation of caffeine in coffee and tea leaves and the human body were summarized in the review.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202400050","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T21:58:11Z","timestamp":1715205491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Caffeine and Purine Derivatives: A Comprehensive Review on the Chemistry, Biosynthetic Pathways, Synthesis\u2010Related Reactions, Biomedical Prospectives and Clinical Applications"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8557-2806","authenticated-orcid":false,"given":"Ameen A.","family":"Abu\u2010Hashem","sequence":"first","affiliation":[{"name":"Photochemistry Department National Research Centre  12622 Dokki Giza Egypt"},{"name":"Chemistry Department, Faculty of Science Jazan University  45142 and 2097 Jazan KSA Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Othman","family":"Hakami","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Jazan University  45142 and 2097 Jazan KSA Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El\u2010Shazly","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy Faculty of Pharmacy Ain Shams University  Cairo 11566 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba A. 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