Total Syntheses of Hikosamine and Hikizimycin

Hikizimycin (1) is a potent anthelmintic and antibacterial natural product. The core 4-amino-4-deoxyundecose sugar (hikosamine) of 1 consists of an 11-carbon linear chain substituted with one amino group and 10 hydroxy groups. The C1 and C6O positions of the 10 contiguous stereocenters are further appended by a cytosine base and a 3-amino-3-deoxyglucose sugar (kanosamine), respectively. Since the structural determination in the early 1970s, synthetic chemists have been attracted by this exceedingly complex structure and have investigated the full chemical construction of 1. These synthetic efforts culminated in four syntheses of the protected hikosamines and two total syntheses of 1. In this Perspective, we summarize the strategies and tactics utilized in these syntheses to showcase the evolution of modern natural product synthesis.