[Creation of functional organic compounds and their applications]

Our studies on creation of functional organic compounds and their applications, have focused on three areas, namely, (A) organic chemical studies on VD (vitamin D) analogues, (B) studies on solitary wasp venoms, and (C) studies on functional building blocks for organic synthesis. In the first area, several novel and important vitamin D analogues were synthesized and biologically evaluated, and their high VDR (vitamin D receptor) binding affinities were discussed on the basis of conformational analysis and docking study by Molecular Mechanics Calculation to the LBD (ligand binding domain) of VDR: These compounds include 24,24-difluoro-1 alpha,25-dihydroxy-VD3 (2) (an antimetabolism agent, the first VD analogue having higher potency than the natural hormone (1)), 2 alpha-methyl-1 alpha,25-dihydroxy-VD3 (42b) (the first A-ring-modified VD analogue exhibiting stronger VDR affinity than 1) and its 20-epimer (43b) (a VD analogue having a highest HL-60 cell differentiation inducing activity with a relatively low calcemic effect), and 2 alpha-(omega-hydroxypropyl)-1 alpha,25-dihydroxy-VD3 (exceptionally high calcemic effect). In the second area, we isolated and determined the structure of pompilidotoxins (76, 77), novel peptide neurotoxins in solitary wasp venoms. In the third area, we created furan-fused 3-sulfolene, 4H, 6H-thieno [3,4-c]-furan 5,5-dioxide and pyrrole-fused 3-sulfolene (96), 3,5-dihydro-1H-thieno[3,4-c] pyrrole 2,2-dioxide (125), and studied their inter- and intramolecular Diels-Alder reactions.