Hirokazu Arimoto

Absolute stereochemistry of halichlorine; A potent inhibitor of VCAM-1 induction

Abstract The absolute stereochemistry of a marine alkaloid halichlorine, which significantly inhibits VCAM-1 induction in HUVE cells, was established by synthesis of a degradation product of natural product.

Isolation and structures of haterumalides NA, NB, NC, ND, and NE, novel macrolides from an Okinawan Sponge Ircinia sp.

Abstract Novel macrolides, haterumalides NA ( 1 ), NB ( 2 ), NC ( 3 ), ND ( 4 ), and NE ( 5 ), were isolated from an Okinawan sponge Ircinia sp. The absolute stereostructure of 1 was determined by spectroscopic analysis and modified Moshers method. Haterumalide NA ( 1 ) showed cytotoxicity against P388 cells and acute toxicity against mice.

Synthesis of pinnaic acid; Asymmetric construction of spirocyclic core

An asymmetric synthesis of the spirocyclic core of pinnaic acid, a cPLA~ inhibitor, is described. A key transformation in the sequence involves an asymmetric Michael-initiated ring closure.

Discovery of a Novel Series of Semisynthetic Vancomycin Derivatives Effective against Vancomycin-Resistant Bacteria

Novel semisynthetic vancomycin derivatives with antibacterial activity against vancomycin-resistant S. aureus (VRSA) were prepared. Replacement of Cl groups of vancomycin by Suzuki-Miyaura cross-coupling reaction, which gave the title compounds, is described for the first time. Introduction of a carbon substituent at the amino acid residue 2 of vancomycin led to an enhancement of antibacterial activity against vancomycin-resistant strains, whereas the additional introduction at the amino acid residue 6 resulted in a reduction in activity even against vancomycin-susceptible strains.

Multi-valent polymer of vancomycin : enhanced antibacterial activity against VRE

A multivalent polymer of vancomycin, synthesized via ring-opening metathesis polymerization (ROMP), exhibited significant enhancement of antibacterial activity against vancomycin-resistant enterococi (VRE).

Synthetic approach to kendomycin: preparation of the C-glycosidic coreElectronic supplementary information (ESI) available: selected spectral data for compounds 7, 8, 10, 11, 12, 15, 16, 17, 18, and 2. See http://www.rsc.org/suppdata/cc/b4/b402391a/

Synthesis of the C13-C19 C-glycoside portion of kendomycin was achieved via oxidative pyran cyclization and Claisen rearrangement to construct the fully functionalized aromatic ring.

8-Nitroguanosines as chemical probes of the protein S-guanylation

Azido- and fluoro- derivatives of 8-nitroguanosine were developed, and will contribute to the exploration of protein S-guanylation by endogenous nitrated nucleosides.

Synthesis of rigidly-linked vancomycin dimers and their in vivo efficacy against resistant bacteria

A novel and efficient avenue for the preparation of dimeric vancomycins is described, and the dimers exhibited excellent antibacterial activities in the murine infection model.

Recent aspects of chemical ecology: Natural toxins, coral communities, and symbiotic relationships

The discovery of new ecologically active compounds often triggers the development of basic scientific concepts in the field of biological sciences, since such compounds have direct physiological and behavioral effects on other living organisms. We have focused on the identification of natural key compounds that control biologically and physiologically intriguing phenomena. We describe three recent aspects of chemical ecology that we have investigated: natural toxins, coral communities, and symbiotic relationships. Blarina toxin (BLTX) is a lethal mammalian venom that was isolated from the short-tailed shrew. Duck-billed platypus venom shows potent Ca2+ influx in neuroblastoma cells. The venom of the solitary wasp contains arginine kinase-like protein and is used to paralyze its prey to feed its larva. The ecological behaviors of corals are controlled by combinations of small molecules. The polyol compound symbiodinolide may serve as a defense substance for symbiotic dinoflagellates to prevent digestion of their host animals. These compounds reveal the wonder of nature, in both terrestrial and marine ecological systems.

Enantioselective Total Synthesis of Pinnaic Acid and Halichlorine

The enantioselective total synthesis of the bioactive marine natural products pinnaic acid and halichlorine is reported in detail. Our total synthesis features the construction of the five-membered ring and C9 and C13 stereogenic centers through a palladium-catalyzed trimethylenemethane [3+2] cyclization; the installation of the nitrogen atom through a regioselective Beckmann rearrangement of a poorly reactive ketone; the stereoselective cyclization of the spiro ring through a four-step, one-pot hydrogenation-cyclization; and efficient connection of the sterically hindered lower chain through a reduced-pressure cross olefin metathesis reaction.