Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide.

A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure-activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Total Synthesis and Antimicrobial Activities of All Stereoisomers of (16 Z,20 E)-Eushearilide and (16 E,20 E)-Eushearilide.

As promising antifungal agents, the eight stereoisomers of eushearilide, including the natural compound, were synthesized relying on an asymmetric Mukaiyama aldol reaction, Julia-Kocienski olefination, and Shiina macrolactonization. Moreover, their in vitro antimicrobial activities against some fungi and bacteria were evaluated by the disk-diffusion method, which revealed that not only natural eushearilide but also its stereoisomers exhibited significant antimicrobial activity against a variety of fungi and bacteria.

Asymmetric Total Synthesis of (-)-Astakolactin and Confirmation of Its Stereostructure.

The originally proposed structure of astakolactin was revised, and an asymmetric total synthesis of the newly proposed structure was achieved. The key transformations in the synthesis were a Johnson-Claisen rearrangement, an asymmetric Mukaiyama aldol reaction, and a Mitsunobu-type cyclodehydration. The spectroscopic data and specific rotation of the compound obtained matched well with those reported for naturally occurring astakolactin.

Total synthesis of the proposed structure of astakolactin.

The first total synthesis of the proposed structure of astakolactin, a sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson-Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization.

4-(Dimethylamino)pyridine N-Oxide-Catalyzed Macrolactamization Using 2-Methyl-6-nitrobenzoic Anhydride in the Synthesis of the Depsipeptidic Analogue of FE399.

A depsipeptidic analogue of FE399 was efficiently synthesized mainly through macrolactamization using 2-methyl-6-nitrobenzoic anhydride (MNBA), and a detailed investigation of the desired 16-membered macrolactam core of FE399 was performed. It was determined that the combination of MNBA and a catalytic amount of 4-(dimethylamino)pyridine N-oxide exhibits much higher activity than that of conventionally used coupling reagents such as hexafluorophosphate azabenzotriazole tetramethyl uronium and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.

Enantioselective total synthesis of naturally occurring eushearilide and evaluation of its antifungal activity.

The asymmetric total synthesis of a newly proposed structure of (3S,16E,20E,23S)-(+)-eushearilide was achieved primarily through an asymmetric Mukaiyama aldol reaction, Schlosser-modified Wittig reaction and 2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. Based on detailed spectroscopic analyses, the obtained synthetic compound was found to be identical to natural eushearilide. Therefore, we were able to determine the true structure of eushearilide. Moreover, the synthetic compound was found to exhibit significant in vitro antifungal activity against various fungi and bacteria.

Identification of the small molecule compound which induces hepatic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (MSCs) are expected to have utility as a cell source in regenerative medicine. Because we previously reported that suppression of the Wnt/ß-catenin signal enhances hepatic differentiation of human MSCs, we synthesized twenty-three derivatives of small molecule compounds originally reported to suppress the Wnt/ß-catenin signal in human colorectal cancer cells. We then screened these compounds for their ability to induce hepatic differentiation of human UE7T-13 MSCs. After screening using WST assay, TCF reporter assay, and albumin mRNA expression, IC-2, a derivative of ICG-001, was identified as a potent inducer of hepatic differentiation of human MSCs. IC-2 potently induced the expression of albumin, complement C3, tryptophan 2,3-dioxygenase (TDO2), EpCAM, C/EBPα, glycogen storage, and urea production. Furthermore, we examined the effects of IC-2 on human bone marrow mononuclear cell fractions sorted according to CD90 and CD271 expression. Consequently, CD90+ CD271+ cells were found to induce the highest production of urea and glycogen, important hepatocyte functions, in response to IC-2 treatment. CD90+ CD271+ cells also highly expressed albumin mRNA. As the CD90+ CD271+ population has been reported to contain a rich fraction of MSCs, IC-2 apparently represents a potent inducer of hepatic differentiation of human MSCs.

Fluorous "racemic" mixture synthesis: polysaccharide-based chiral columns for simultaneous demix and enantioseparation of racemic fluorous tagged compounds.

The proof of concept experiments of fluorous "racemic" mixture synthesis (FRMS) is shown using polysaccharide-based chiral stationary phases. The mixture of racemic O-benzoylmandelate derivatives bearing different lengths of fluorous cleavable tags undergoes sequential reactions to provide individual derivatives as well as their enantiomers resolved on polysaccharide-based chiral HPLC columns (DAICEL CHIRALCEL and CHIRALPAK series).