Kiyomatsu Hashizume

Total synthesis of (±)-surugatoxin☆

Abstract Total synthesis of surugatoxin 1 , isolated from the toxic Japanese ivory shell ( Babylonia japonica ), was achieved from 6-bromoisatin by a stepwise ring construction involving two key steps: the stereospecific cyclization ( 17 → 18 ) and hydration ( 33b → 1 ).

Effects of phthalate ester derivatives including oxidized metabolites on coactivator recruiting by PPARα and PPARγ

Phthalate esters (PEs), a group of environmental chemicals, affect biological systems via endocrine and lipid metabolism modulations. These effects are believed to be mediated in part by peroxisome proliferator-activated receptors (PPARs). Evaluations of PE activities as ligands toward PPARs have been investigated in many studies on their primary metabolites, monoesters. However, the activities of various other metabolites, including oxidized derivatives, remain to be determined. Here, we have evaluated the PPAR ligand activities of these PE derivatives by in vitro coactivator recruiting assay. Mono(2-ethyl-5-hydroxyhexyl)phthalate, the most abundant metabolite of di-(2-ethylhexyl)phthalate (DEHP), was less active than mono(2-ethylhexyl)phthalate (MEHP) as a PPAR ligand. Other derivatives oxidized at the alkyl group and benzene ring of DEHP, MEHP, dibutyl phthalate and its monoester were also investigated and some affected PPAR activities. Unexpectedly, MEHP as well as its further oxidized metabolite did not show clear activity for PPARalpha, although MEHP is believed to interact with PPARalpha. This might imply indirect PPAR-mediated mechanisms that lead to observed biological effects such as peroxisome proliferation.

Total synthesis of (-+)-surugatoxin

Abstract Total synthesis of surugatoxin 1, isolated from the toxic Japanese ivory shell ( Babylonia japonica ), was achieved from 6-bromoisatin by stepwise ring construction involving two key steps: the stereospecific cyclization (9→10) and hydration (17→1).

Model experiments on surugatoxin synthesis. an approach in the construction of the pentacyclic ring system

Synthesis of the ethyl ester 2a of the debromo-aglycone of surugatoxin 1 has been achieved in 10 steps starting from readily available ethyl 2-(2-oxo-3-indolenyl)-3-oxo-4-phthalimidobutyrate 3.

Determination of Butylated Hydroxyanisole and Its Conjugated Metabolites in the Organs, Blood and Excreta of Mice by High-Performance Liquid Chromatography

The determination of butylated hydroxyanisole (BHA) and its conjugated metabolites (glucuronide and sulfate) in tissues and excreta of BHA administered mice was investigated by normal-phase high-performance liquid chromatography (HPLC). Male mice were orally administered BHA at 50 and 500 mg/kg, BHA and its metabolites were extracted from the liver and kidney by continuous extraction and from the blood, stomach, intestine, urine and feces by direct extraction. Conjugated metabolites were hydrolyzed with enzymes before extraction. BHA could be determined without influence from obstructive substances. In animals administered BHA at 500 mg/kg, unchanged BHA was present at high concentration in the liver, kidney and the blood 0.5 h later, but at 8 h could not be detected in any sample. The sulfate of BHA exceeded the glucuronide of BHA in the liver at 0.5 h, but the latter exceeded the former during 1 and 3 h after dosing. Mice excreted about 52% of 500 mg/kg during 8 h, and about 76% within 48 h in the urine as glucuronide (72.3±7.6%), sulfate (3.0±2.4%) and unchanged BHA (0.3±0.1%). However, about 25% of unchanged BHA was recovered from stomach at 8 h, and even after 48 h. some unchanged BHA could be found.