Synthesis of a Ring-Oxygenated Variant of the 2-Carboxy-6-hydroxyoctahydroindole Core of Aeruginosin 298-A from Glucose

• Published in: Journal of organic chemistry 2005-10, Vol.70 (22), p.8687-8692
• Main Authors: Nie, Xiaoping, Wang, Guijun
• Format: Article
• Language: English
• Subjects: Alkylation; Bromides - chemistry; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Crystallography, X-Ray; Exact sciences and technology; Glucose - chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Indoles - chemistry; Leucine - analogs & derivatives; Leucine - chemical synthesis; Leucine - chemistry; Magnetic Resonance Spectroscopy; Malonates - chemistry; Methylation; Models, Molecular; Molecular Structure; Oligopeptides - chemistry; Organic chemistry; Oxidation-Reduction; Preparations and properties; Protein Structure, Tertiary; Protons; Substrate Specificity; Thrombin - antagonists & inhibitors; Thrombin - chemistry; Thrombin - metabolism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0507901

The design and synthesis of a new core structure, a ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole (Choi) from d-glucose, is reported. Choi, a rigid bicyclic unnatural amino acid, is the core structure of about 15 aeruginosins natural compounds. These compounds are thrombin, trypsin, and factor VIIa inhibitors and Choi is important for their biological activity. The ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole can potentially be used as a surrogate of Choi in the design and synthesis of aeruginosin-based thrombin inhibitors.