Efficient Formal Synthesis of the Human Telomerase Inhibitor (±)-γ-Rubromycin

• Published in: Angewandte Chemie (International ed.) Vol. 48; no. 43; pp. 7996 - 8000
• Main Authors: Rathwell, Dominea C.K, Yang, Sung-Hyun, Tsang, Kit Y, Brimble, Margaret A
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 12-10-2009; WILEY‐VCH Verlag
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; antibiotics; azides; Benzene Derivatives - chemistry; Crystallography, X-Ray; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Humans; Isocoumarins - chemistry; Molecular Conformation; Naphthoquinones - chemistry; natural product synthesis; Quinones - chemical synthesis; Quinones - chemistry; spiroketals; Telomerase - antagonists & inhibitors; Telomerase - metabolism; total synthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200903316

Balancing act: The correct balance of electronic factors in the naphthazarin and isocoumarin fragments facilitates the acid‐mediated spiroketalization step to afford the key densely functionalized spiroketal (see picture; EOM=ethoxymethyl) in the formal synthesis of (±)‐γ‐rubromycin. A novel regioselective allyloxylation/Claisen rearrangement of 2‐azido‐1,4‐naphthoquinone provides access to the highly oxygenated naphthazarin fragment.