Asymmetric Total Synthesis of (−)-Saframycin A from l-Tyrosine

• Published in: Journal of organic chemistry 2011-07, Vol.76 (13), p.5363-5368
• Main Authors: Dong, Wenfang, Liu, Wei, Liao, Xiangwei, Guan, Baohe, Chen, Shizhi, Liu, Zhanzhu
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemical synthesis; Antibiotics, Antineoplastic - chemistry; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic agents; Biological and medical sciences; Chemistry; Exact sciences and technology; General aspects; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Medical sciences; Molecular Conformation; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Stereoisomerism; Tyrosine - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo200758r

The asymmetric total synthesis of (−)-saframycin A, a natural antitumor product of the tetrahydroisoquinoline antitumor antibiotics family, has been accomplished by employing l-tyrosine as the starting chiral building block in 24 steps for the longest linear sequence in an overall yield of 9.7%. The key steps in the synthesis involve stereoselective intermolecular and intramolecular Pictet–Spengler reactions, which induced the correct stereochemistry at C-1 and C-11, respectively. The selective protection–deprotection protocol of an amino group in the two-step transformation from intermediate 10 to 12 and a hydroxyl group in the first two steps resulted in both high selectivity and efficiency of the synthetic route.