Asymmetric Synthesis of Pantolactone: Recent Advances

• Published in: European journal of organic chemistry 2023-12, Vol.26 (46), p.n/a
• Main Authors: Du, Zhi‐Hong, Lv, Xiao‐Xiong, Liu, Ning, Chen, Fei, Yuan, Meng, Da, Chao‐Shan
• Format: Article
• Language: English
• Subjects: (R)-pantolactone; asymmetric synthesis; Asymmetry; biocatalysis; Catalysis; Chemical synthesis; chiral organocatalysis; Food additives; ketopantolactone; Reagents
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300918

(R)‐Pantolactone, an intermediate in the syntheses of Vitamin B5 and coenzyme A, is an important chiral molecule often used as a food additive, chiral auxiliary, and chiral starting material for organic transformations. Enantioenriched pantolactones are predominantly produced by biological fermentation and chemical synthesis approaches. Herein, we present a review of recent developments in the asymmetric synthesis of pantolactone through different methods, and systematically summarize the characteristics and advantageous features of these strategies. Among the strategies discussed herein, the direct asymmetric catalysis of glyoxylate and isobutyraldehyde with small organocatalyst molecules has attracted growing attention owing to its good step‐economy, commercially available starting materials, absence of toxic reagents, mild reaction conditions, convenient operation, and low catalyst loading. These characteristics render the direct asymmetric route to pantolactone a particularly attractive procedure. This review provides valuable guidance for the design and synthesis of enantioenriched pantolactone and its analogs. Recent advances in the asymmetric synthesis of pantolactone are reviewed and the advantages and disadvantages of common synthetic strategies are highlighted. Among these strategies, direct asymmetric catalysis using small organic molecules as catalysts is an extremely promising approach for the industrial synthesis of D‐pantolactone owing to its high step‐economy, commercially available starting materials, avoidance of toxic reagents, mild reaction conditions, and convenient operation. This review offers valuable insights and recommendations for the design and synthesis of enantioenriched pantolactone and its analogs, providing new and useful guidance in the field.