Results in Chemistry (Jan 2021)
Total synthesis of selected bioactive alkaloids, their structure–function relationships and molecular target interactions: A comparative synthetic analysis of tryptophan originated chiral pool approaches vs other synthons
Abstract
The use of tryptophan as an inexpensive and versatile chiral pool for alkaloid synthesis continues to influence modern synthetic chemistry. In this review, we summarized comparative strategies of tryptophan based alkaloids for the construction of architecturally complex bioactive natural compounds using tryptophan-derived chiral synthons versus non-tryptophan routes based on the basis of atom economy, overall chemical yield, stereoselectivity and sustainability. We also briefly discussed the Structure-activity relationship of selected tryptophan-based alkaloids & their modified analogous to elevate the effects of bioactive compounds in a broad spectrum of pharmacological effects. Tryptophan has an inherent chirality which makes it a great advantage as a cheap Chiron having functionalizable groups (–CO2H, –NH2 and indole) and ensures at least one fixed chiral center which governs the installation of another stereogenic center in metal and organocatalyzed asymmetric synthesis. On the contrary, the non-tryptophan route utilizes an external chiral source to generate chirality in the molecule. In this approach, metal and organometallic catalysts are used in numerous synthetic transformations. With green chemistry approach being the need of the hour in industry and research laboratories, atom economic and sustainable synthetic strategies for the total synthesis of bioactive Tryptophan-derived alkaloids will be a guiding path forward.
