Total Synthesis of Galbulimima Alkaloids: Himgaline and Gb13

For thousands of years nature has played an important role in providing mankind with life-saving drugs. Several natural products have been clinically approved and they continue to remain as valuable medicines. However, in cases where the supply of an active natural product is limited, total synthesis is often the only means by which sufficient quantities could be generated for therapeutic use. Additionally, such a process could unveil novel pharmacophores which could serve as templates for designing new drugs. Himbacine, himgaline, and GB13 belong to a family of alkaloids isolated from the bark of a rain forest tree, Galbulimima belgraveana. While himbacine has been extensively studied for its antimuscarinic activity, the biological properties of its more complex congeners remain unexplored. This book describes total syntheses of both the enantiomers of himgaline and GB13. Key manipulations involved a Diels-Alder reaction, an aldol-type cascade cyclization, an aza-Michael reaction, and a hydroxyl-directed stereoselective ketone reduction. This synthetic achievement paves the way for future exploration of the medicinal value of compounds described herein and other related natural products.