20485-01-2Relevant articles and documents
Antiviral agents. Chemical modifications of a disulfide antibiotic, acetylaranotin
Murdock
, p. 827 - 835 (1974)
The reactivity of the cyclic disulfide linkage in acetylaranotin was investigated. Novel insertion reactions with elemental sulfur and hydrogen cyanide gave a tetrasulfide and a dithiocarbamate. Cleavages with methanethiol and dimethyl disulfide gave a dithiol and a bis(methyl disulfide). In mice, the tetrasulfide and a trisulfide gave protection equivalent to that of acetylaranotin against a lethal respiratory virus, Coxsackie A 21. Carbethoxy derivatives were less active. Marginal activities of a trithiocarbonate and a monosulfide give the first indication that an S S linkage may not be an absolute requirement for antiviral activity in this family of compounds. In an enzyme inhibition assay against an RNA polymerase system from Coxsackie A 21 virus, several compounds were more than 1000 times more inhibitory toward the viral polymerase than they were toward the RNA polymerase of the uninfected host cells. An improved color test for detection of thiols is described.
Total synthesis of (-)-Acetylaranotin
Fujiwara, Hideto,Kurogi, Taichi,Okaya, Shun,Okano, Kentaro,Tokuyama, Hidetoshi
, p. 13062 - 13065 (2013/02/26)
Epidithiodiketopiperazines are an important class of natural products because of their unique structural and biological properties. Among them, acetylaranotin (1), SCH64874 (2), compound 3, emethallicin A (4), MPC1001 (5), and emestrin (6) feature a dihydrooxepine moiety fused to a pyrrolidine/ epidithiodiketopiperazine (Figure 1). They also display a range of intriguing biological activities, such as: inhibitory activity against viral RNA polymerase, antagonistic activity of epidermal growth factor receptor, potent antituberculous activity, inhibitory activity against histamine release, antiproliferative activity against DU145 human prostate cancer cell line, and antagonistic activity of chemokine receptor (CCR2). While numerous synthetic approaches were investigated, only a limited number of successful preparations of the characteristic dihydrooxepine ring have been reported. During the synthetic studies on MPC1001, Peng and Clive established a synthetic method for a pyrrolidinone-fused dihydrooxepine through tetrahydrooxepine formation followed by selenoxide elimination.
Enantioselective total synthesis of (-)-acetylaranotin, a dihydrooxepine epidithiodiketopiperazine
Codelli, Julian A.,Puchlopek, Angela L. A.,Reisman, Sarah E.
supporting information; experimental part, p. 1930 - 1933 (2012/03/11)
The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (-)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (-)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family.
