A Diels–Alder Reaction for the Total Synthesis of the Novel Antibiotic Antitumor Agent Mensacarcin

Abstract

The antibiotic mensacarcin (1), which contains nine stereogenic centers and two epoxy functionalities, is a novel antitumor agent that was first isolated from the culture broth of Streptomyces sp. Gö C4/4 found in a soil sample next to the northern cafeteria of the University of Göttingen. For the synthesis of 1 and related structurally simplified analogs, aDiels–Alder reaction of O‐methyljuglone (11) and the tetrasubstituted 1,3‐butadiene 22 was performed to give the cycloadduct rac‐28, which was transformed into the epoxides rac‐31 and rac‐33. The cytotoxicity of rac‐33 is only 53 times lower than the much more complex 1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae

“…The synthesis of juglone (6) was started from commercially available 1,5-hydroxynaphthalene, which was oxidized with air in the presence of CuCl in the dark to give 6 in 47% yield. 11 Chemical transformations of 6 to 8 was carried out according to the reported methods 12 with some modifications. Oxidative amination of 6 with dimethylamine (2.0 M solution in THF) in toluene at À40°C gave 2-dimethylaminojuglone (7a) and 3-dimethylaminojuglone (7b) in 42% and 11% yields, respectively.…”

Structure‐activity relationship studies on naphthoquinone analogs. The search for new herbicides based on natural products

“…Modifications carried out at position 5 of the naphthoquinone backbone were made using the corresponding side‐chain and silver(I) oxide. Derivatives 16 – 19 and 21 were synthesized according to the methodology described by O'Keefe et al and derivative 20 was prepared according to the procedure reported by Tietze et al with some modifications, as described above. These compounds were obtained in moderate‐high yield (24–83%) (Fig.…”

Influence of lipophilicity in O‐acyl and O‐alkyl derivatives of juglone and lawsone: a structure–activity relationship study in the search for natural herbicide models

“…with some variations (Fig. ) . Silver(I) oxide and the corresponding alkyl iodide were added in a slight excess (1.3 equiv.)…”

“…Ten compounds were prepared by modifying the 5‐position of the naphthoquinone moiety. These compounds were synthesized according to a literature procedure with some modifications . The corresponding alkyl iodide (0.765 mmol, 1.3 equiv.)…”

“…These compounds were synthesized according to a literature procedure with some modifications. 20 The corresponding alkyl iodide (0.765 mmol, 1.3 equiv.) was added dropwise to a mixture of juglone (1) (100 mg, 1 equiv.)…”