Misc

TA1, a new triterpenoid acid was isolated from the myxomycete Tubulifera arachnoidea, and its structure was elucidated by spectral data. However, the stereochemistry of the position of 22 and 23, diol moiety of side chain, couldn't be determinated in comparison with the data of papers. Then our purpose is determination of these stereochemistry in comparison with the spectral data of the synthetic model compounds, four diasteromers with the similar side chain. Syn diol model compounds were synthesized from stigmasterol. These spectral data had a significant difference and were suitable for comparison with the data of TA1. The opening of epoxide to provide anti diol model compounds is now under way.

A novel peptide lactone, melleumin A, and its seco acid methyl ester, melleumin B, were isolated from cultured plasmodium of the myxomycete Physarum melleum. We studied the total synthesis of melleumin A and B. Melleumin A and B consist of four residues, p-methoxybenzoic acid, L-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid. Total synthesis of melleumin B was achieved by a stereoselective method, which provided further evidence for the all absolute stereochemistry of melleumin B. The Wnt signal inhibitory actives of melleumin B and its 10-epimer were evaluated. 10-epimer of melleumin B showed moderate inhibition of Wnt signal transcription.

During our studies in a search for natural products from myxomycetes, we have isolated a novel peptide lactone, melleumin A , and its seco acid methyl ester, melleumin B , from the cultured plasmodium of the myxomycete Physarum melleum. We studied the total synthesis of melleumin A, B and their diastereomers. Melleumin A and B consist of four residues, p-methoxybenzoic acid, L-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid. Total synthesis of melleumin A, B and their diastereomers were achieved by a stereoselective method. The Wnt signal inhibitory activities of melleumin A, B and their diastereomers were evaluated. The 3R-epimer, 10R-epimer and (3R, 4S, 10R, 11R)-isomer of melleumin B showed moderate inhibition of the Wnt signaling pathway.

1α,25-Dihydroxyvitamin D3(1) has a wide range of biological activities, for example, calcium and phosphorus homeostasis, cell growth and differentiation. The actions of 1 are mediated by a specific nuclear receptor, vitamin D receptor (VDR). Hydrogen bonds between three hydroxyl groups of 1 and hydrophilic amino acids in the ligand-binding domain (LBD) of VDR are essential for its actions. Arginine 274 is known to form hydrogen bond with 1α-OH of 1, and its mutation lead to loss of the affinity and its actions. For the mutant VDR we designed the analogs having a CH3 or HOCH2 group on its 1α-position to effect hydrophobic interaction. A coupling reaction of CD ring bromoolefin and A ring enyne was carried out by the method developed by Trost. A ring enynes for 1α-CH3 and 1α-HOCH2 analogs were prepared from D-galactose and D-glucose, respectively.

During our studies on a search for natural products from myxomycetes, we have isolated novel compounds, Fuligocandin A and B containing cycloanthranilylproline skeleton, from the extract of fruit bodies of Fuligo candida. Fuligocandin B consists of three residues, anthranilic acid, L-proline, and indole-3-carboxyaldehyde. Enantioselective total synthesis of Fuligocandin A, B were achieved. Moreover we synthesized 11a-CH3 derivatives of Fuligocandin A, B. Fuligocandin B and its derivatives have TRAIL-resistance-overvoming activities on the AGS cells. For construction of the Fuligocandin B chemical library to find new active compounds, solid-phase reactions were examined.