Stereodivergent Syntheses of All Stereoisomers of (−)‐Shikimic Acid: Development of a Chiral Pool for the Diverse Polyhydroxy‐cyclohexenoid (or ‐cyclohexanoid) Bioactive Molecules

• Published in: European journal of organic chemistry 2021-08, Vol.2021 (30), p.4318-4332
• Main Authors: He, Yun‐Gang, Huang, Yong‐Kang, Xu, Zhang‐Li, Xie, Wen‐Jing, Luo, Yong‐Qiang, Li, Feng‐Lei, Zhu, Xing‐Liang, Shi, Xiao‐Xin
• Format: Article
• Language: English
• Subjects: Chiral pool; Cyclitol; NMR; Nuclear magnetic resonance; Shikimic acid; Stereochemistry; Stereodivergent synthesis; Stereoisomerism; Stereoisomers; Synthesis
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202100653

Novel stereodivergent total syntheses of all the seven stereoisomers of (−)‐shikimic acid [(−)‐SA 1] have been systematically performed. (+)‐ent‐SA ent‐1 was synthesized from (−)‐SA 1 via 9 steps in 31 % overall yield; (−)‐3‐epi‐SA 2 was synthesized from (−)‐SA 1 via 5 steps in 66 % overall yield; (+)‐3‐epi‐ent‐SA ent‐2 was synthesized from (−)‐SA 1 via 7 steps in 43 % overall yield; (−)‐4‐epi‐SA 3 was synthesized from (−)‐SA 1 via 11 steps in 32 % overall yield; (+)‐4‐epi‐ent‐SA ent‐3 was synthesized from (−)‐SA 1 via 7 steps in 42 % overall yield; (−)‐5‐epi‐SA 4 was synthesized from (−)‐SA 1 via 6 steps in 56 % overall yield; and (+)‐5‐epi‐ent‐SA ent‐4 was synthesized from (−)‐SA 1 via 12 steps in 29 % overall yield. The stereochemistry of all the above seven stereoisomers of (−)‐SA 1 were further studied by two dimensional (2D) 1H NMR technique. (−)‐Shikimic acid [(−)‐SA 1] is a naturally‐abundant product from Chinese star anise. All of the seven stereoisomers [i. e. (+)‐ent‐SA ent‐1, (−)‐3‐epi‐SA 2, (+)‐3‐epi‐ent‐SA ent‐2, (−)‐4‐epi‐SA 3, (+)‐4‐epi‐ent‐SA ent‐3, (−)‐5‐epi‐SA 4 and (+)‐5‐epi‐ent‐SA ent‐4] have been systematically synthesized from (−)‐SA 1.