In our screening program on immunomodulatory constituents from fungi, many immunosuppressive metabolites have already been isolated from various Ascomycetes belonging to Gelasinospora, Diplogelasinospora, Microascus, Emericella, Eupenicillium, Chaetomium, and Zopfiella. 2) The EtOAc extract of a Fungi Imperfecti, Trichurus terrophilus SWIFT & POVAH showed an appreciable suppressive effect on the proliferation (blastogenesis) of mouse splenic lymphocytes stimulated with mitogens, concanavalin A (Con A), and lipopolysaccharide (LPS). Solvent partitions followed by repeated chromatographic fractionations of the extract, guided by immunosuppressive activity, afforded eleven new compounds tentatively named TT-1-11 (1-11). This paper deals with the structures and immunosuppressive activities of these constituents.The EtOAc extract of T. terrophilus IFM4606 3) cultivated on sterilized moistened-rice medium suppressed the Con Ainduced proliferation of mouse splenic lymphocytes by 99.6% at 50 mg/ml. The EtOAc extract was partitioned between n-hexane and water into an n-hexane layer and an aqueous suspension. The aqueous suspension was further partitioned between EtOAc and water into an EtOAc layer and an aqueous layer [yields (%) of the n-hexane, EtOAc, and aqueous layers after evaporation of the solvents from the EtOAc extract: 73.2, 17.4, and 2.3, respectively]. The IC 50 values of the n-hexane, EtOAc, and aqueous layers against the Con A-induced proliferation were 9.7, 2.5, and Ͼ50 mg/ml, respectively. Repeated chromatographic fractionations monitored by the immunosuppressive activity of the EtOAc layer afforded four components tentatively named TT-1-4 (1-4) [yields (%) of 1, 2, 3, and 4 from the EtOAc extract: 0.26, 0.0078, 0.011, and 0.0089, respectively]. It was found out that the other strain of this fungus, T. terrophilus IMI462513) also produced 1 and its homologues in good yields. Repeated chromatographic fractionations of the EtOAc layer, which was obtained from the partition of the EtOAc extract of T. terrophilus IMI46251 in the same way as described for the partition of the EtOAc extract of T. terrophilus IFM4606, gave seven new constituents tentatively named TT-5-11 (5-11) in addition to 1-4 [yields (%) of 1, 2, 3, 4, 5, a mixture of 6 and 7 (6/7), 8, 9, 10, and 11 from the EtOAc extract: 1. C-NMR spectral data of 1 (see Table 1) including the two dimensional 1 H-1 H shift correlation (COSY), 1 H-detected heteronuclear correlation through multiple quantum coherence (HMQC), and 1 H-detected heteronuclear multiple-bond correlation (HMBC) NMR data suggested a planar structure for TT-1. On acetylation with acetic anhydride in pyridine, 1 gave diacetate (12). Comparison of the 1 H-and 13 C-NMR spectral data of 1 with those of 12 (Table 1) in reference to the acetylation shift rule, 4,5) confirmed the planar structure of TT-1 (1a) (see Fig. 1 (Table 1) with those of 1 revealed that the unsaturated CϭC bond at position 3 in 1 was saturated in 2, indicating that the planar structure of TT-2 was expressed as 2 (F...

Eleven New 2-Pyrones from a Fungi Imperfecti, Trichurus terrophilus, Found in a Screening Study Guided by Immunomodulatory Activity. -Solvent partitions followed by repeated chromatographic fractionations of the Et-O-Ac extract of T. terrophilus, guided by immunosuppressive activity, affords eleven new pyrones such as (I) and (II), tentatively named TT-1-11. Pyrones (Ia)-(Ic) and (II) display considerably high immunosuppressive activities while compounds (If)-(Ih) are of moderate activity. The structure-activity relationships of these constituents are discussed. -(FUJIMOTO*, H.; OKAMOTO, Y.; SONE, E.; MAEDA, S.; AKIYAMA, K.; ISHIBASHI, M.; Chem. Pharm. Bull. 53 (2005) 8, 923-929; Grad. Sch. Pharm. Sci., Chiba Univ., Inage, Chiba 263, Japan; Eng.) -H. Hoennerscheid 03-208