Angucyclinone antibiotics: total syntheses of YM-181741, (+)-ochromycinone, (+)-rubiginone B2, (-)-tetrangomycin, and MM-47755.
A concise and highly enantioselective route has been developed for the synthesis of angucyclinone-type natural products. Utilizing this strategy, total syntheses of five natural products YM-181741, (+)-ochromycinone, (+)-rubiginone B2, (-)-tetrangomycin, and MM-47755 have been accomplished in 22%, 23%, 19%, 18%, and 12% overall yields, respectively. Our approach for the synthesis of these natural products having the benz[a]anthraquinone skeleton is based on a sequential intramolecular enyne metathesis, intermolecular Diels-Alder reaction (DAR), and aromatization. The intramolecular enyne metathesis reaction was employed for the synthesis of enantiopure 1,3-dienes in excellent yields. Furthermore, the synthesis of YM-181741 as well as structurally similar angucyclinones such as (+)-ochromycinone and (+)-rubiginone B2 was achieved via asymmetric enolate alkylation of an oxazolidinone in excellent de. The related angucyclinones (-)-tetrangomycin and MM-47755, bearing a labile tertiary alcohol, were synthesized via Sharpless asymmetric epoxidation of a known allylic alcohol followed by opening the epoxide with Red-Al. The introduction of oxygen functionality at C-1 in all these natural products was accomplished by photooxygenation under a positive pressure of oxygen.
Kaliappan
Krishna P
KP
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400076, India. kpk@chem.iith.ac.in
Ravikumar
Velayutham
V
D000880:Anthraquinones / Q000138:chemical synthesis*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001551:Benz(a)Anthracenes / Q000138:chemical synthesis; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism; D000095602:Angucyclines and Angucyclinones
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001551:Benz(a)Anthracenes; D010100:Oxygen; C451493:YM 181741; C510997:angucyclinone; C510996:rubiginone B2; D000095602:Angucyclines and Angucyclinones; C059960:MM 47755; C103671:tetrangomycin; C510995:ochromycinone