This Total Synthesis will help you Master Organic Chemistry

Natural products are not created equal: some become breast cancer drugs; others only manage to make lettuce seedlings slightly uncomfortable. What about Punctaporonin U? It lacks any biological activity but it makes this up with an impressive cage-like, pentacyclic structure featuring eight contiguous stereocenters. More than enough reason for synthetic chemists to try to make it in the lab! In this video, we discuss the first enantioselective synthesis of this natural product reported by Zhu and co-workers. Doing so, we'll review our basic organic chemistry reaction toolkit and also learn about advanced concepts like retrosynthesis and stereochemistry. Should be enjoyable for any chemistry student! ➡️ Check out "Periodic Tales - The Freshman Mole" (+ preview pages) https://total-synthesis.com/freshman-... 👉 Follow for updates on random research, mechanism quizzes and interesting news!   / totalsynthesis_official   00:00 Digging and shrubbing for gems: Punctaporonin U 02:06 Retrosynthetis Part 1: Strategy and ketone fun 04:54 Retrosynthesis Part 2: Disconnecting the rings 07:15 Forward synthesis Part 1 09:23 Organic chemistry practice problems on total-synthesis.com 09:37 Forward synthesis Part 2: Diastereoselectivity and more reactions 13:22 Forward synthesis Part 3: Domino reaction craziness 16:14 One heck of an experimental procedure 17:10 Endgame 18:59 Wrap-up and THANK YOU Key references: Concise Enantioselective Total Synthesis of (+)-Punctaporonin U | J. Am. Chem. Soc. 2025, 147, 40106 Caryophyllene Sesquiterpenes from a Chaetomium globosum Endophyte of the Canadian Medicinal Plant Empetrum nigrum | J. Nat. Prod. 2023, 86, 1615 On the diastereofacial selectivity of Lewis acid-catalyzed carbon-carbon bond forming reactions of conjugated cyclic enones bearing electron-withdrawing substituents at the .gamma.-position | J. Org. Chem. 1991, 56, 387 A Facile One-step Synthesis of cis-2-Cyclopentene- and cis-2-Cyclohexene-1,4-diols from the Corresponding Cyclodienes | Synthesis 1974; 1974(12): 876 (DOI: 10.1055/s-1974-23462) Recommended organic chemistry books: Winter; Organic Chemistry I For Dummies (start here if you are absolutely friggin clueless) | https://amzn.to/4fmF97q Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge) | https://amzn.to/4ul57ft Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis) | https://amzn.to/4fmF97q | https://amzn.to/3Q529xn Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions) | https://amzn.to/43cbzKH Grossmann; The Art of Writing Reasonable Organic Reaction Mechanisms (building intuition for intermediate and advanced reaction mechanisms) | https://amzn.to/4dOiIXA Nicolaou; Classics in Total Synthesis 1-4 (simply legendary series) | https://amzn.to/4o986pz | https://amzn.to/3ROsRLp | https://amzn.to/3S4vCYV | https://amzn.to/4dPI9YL Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life) | https://amzn.to/4odZwWW Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures) | https://amzn.to/4dZk9kH Anslyn; Modern Physical Organic Chemistry (almost anything you will need for (organic) physical chemistry) | https://amzn.to/4ul57ft