Total Synthesis of Terprenin, a Novel Immunosuppressive p-Terphenyl Derivative

Abstract

We achieved a total synthesis of terprenin, a novel potent immunoglobulin E antibody suppressant which was obtained from the fermentation broth of Aspergillus candidus RF-5672 and has a highly oxygenated p-terphenyl skeleton with a prenyloxy side chain. The key steps relied on the Suzuki reaction to construct the terphenyl skeleton and on regioselective halogenations to selectively combine the aromatic rings. The highly efficient and practical production of this important natural product offers promise for the development of a new type of antiallergic drug.

Sarcodonins and Sarcoviolins, Bioactive Polyhydroxy‐p‐terphenyl Pyrazinediol Dioxide Conjugates from Fruiting Bodies of the Basidiomycete Sarcodon leucopus

“…[6] Until recently, fully aromatic polyhydroxyp-terphenyls have been reported less frequently than their related terphenylquinones, which are well-known as fungal pigments. Recent additions to this group include promising bioactive metabolites such as the potent immunoglobulin E antibody suppressant terprenin, [7,8] obtained from cultures of Aspergillus candidus, the anti-insect and cytotoxic compounds obtained from the sclerotia of A. arenarius [9] and Penicillium raistrickii, [10] as well as the benzofuranoid terphenyls Bl-I to Bl-V from fruiting bodies of Boletopsis leuc-matography on a column of silica gel. Chromatography on acetylated polyamide and Diol Si gel has allowed the isolation of 3, which has been studied mainly as its more-stable peracetate 12.…”

Studies on Naturalp-Terphenyls: Total Syntheses of Vialinin A and Terrestrin B

“…In our studies, the aryl triflate was highly oxgenated and electron-rich. [29][30][31] In order to confirm whether the coupling reaction using such a triflate with boronic acids would proceed without trouble or not, we examined Suzuki-Miyaura coupling of 21 with 7-9 under a variety of conditions (Scheme 3). The use of palladium acetate 32) in the presence of triphenylphosphine and sodium carbonate gave good results as shown in Table 1 (entries 2, 5,8), although the TBS group was removed in one case (entry 2).…”

“…The residue was chromatographed on silica gel (n-hexane-ethyl acetate ¼ 50 : 1 (29). Tetrakis(triphenylphosphine)palladium (2.3 mg, 1.9 mmol) was added to a stirred mixture of 8 (36.5 mg, 0.16 mmol), 21 (21.5 mg, 0.04 mmol), and cesium carbonate (52.1 mg, 0.16 mmol) in toluene (1.5 ml), and the mixture was stirred at 100 C for 20 h. The treatment described for the preparation of 22 yielded 24 (15.1 mg, 62%), 26 (3.8 mg, 22%), and 29 (1.4 mg, 7%) 5,6-Bis(phenylacetoxy)-4,7-bis-(p-(methoxy)phenyl)benzo [1,3]dioxole (31). To a stirred solution of 25 (137 mg, 0.30 mmol) in dichloromethane (2.0 ml) was added a 10% HCl solution in methanol (2.0 ml), and the mixture was stirred at rt for 11 h and then concentrated.…”

A new practical tritium labelling procedure using sodium borotritide and tetrakis(triphenylphosphine)palladium(0)

“…A potent IgE suppressant, Terprenin, 18 was 3 H-labelled in one step without damage to the prenyl group, as shown in Figure 9, for the studies on bio-reaction mechanism of the IgE suppressant.…”