Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H).
The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño's protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I.
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. yokoya@my-pharm.ac.jp.
Masashi
M
Yokoya
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. k.koba0222@gmail.com.
Keiichiro
K
Kobayashi
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. m146212@std.my-pharm.ac.jp.
Mitsuhiro
M
Sato
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. naoki@my-pharm.ac.jp.
Naoki
N
Saito
D000818:Animals; D016227:Benzoquinones / Q000737:chemistry; D047129:Haliclona / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D064588:Selenium Oxides / Q000737:chemistry; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000737:chemistry*
D016227:Benzoquinones; D007546:Isoquinolines; D010879:Piperazines; D064588:Selenium Oxides; D044005:Tetrahydroisoquinolines; C412688:cribrostatin 4; C561143:renieramycin I; D000077489:Piperazine; C004532:quinone
cribrostatin 4 (renieramycin H); marine natural product; renieramycin I; selenium oxide oxidation; structural determination; total synthesis