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Biomedical subjects

Jun Ishihara

Publications and source records attributed to Jun Ishihara.

12 recordsLinked to original sources
PubMed2007

Synthesis and biological evaluation of a 3-positon epimer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)(2)D(3). ED-71 has potent biological effects on bone and is currently under phase III clinical studies for bone fracture prevention. It is well-known that the synthesis and secretion of parathyroid hormone (PTH) is regulated by 1,25(OH)(2)D(3). Interestingly, during clinical development of ED-71, serum intact PTH in osteoporotic patients did not change significantly upon treatment with ED-71. The reason remains unclear, however. Brown et al. reported that 3-epi-1,25(OH)(2)D(3), an epimer of 1,25(OH)(2)D(3) at the 3-position, shows equipotent and prolonged activity compared to 1,25(OH)(2)D(3) at suppressing PTH secretion. Since ED-71 has a bulky hydroxypropoxy substituent at the 2-position, epimerization at the adjacent and sterically hindered 3-position might be prevented, which may account for its weak potency in PTH suppression observed in clinical studies. We have significant interest in ED-71 epimerization at the 3-position and the biological potency of 3-epi-ED-71 in suppressing PTH secretion. In the present studies, synthesis of 3-epi-ED-71 and investigations of in vitro suppression of PTH using bovine parathyroid cells are described. The inhibitory potency of vitamin D(3) analogs were found to be 1,25(OH)(2)D(3)>ED-71> or =3-epi-1,25(OH)(2)D(3)>>3-epi-ED-71. ED-71 and 3-epi-ED-71 showed weak activity towards PTH suppression in our assays.

Animals↗
PubMed2006

Synthesis and evaluation of a 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).

A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling the A-ring fragment (5) with the C/D-ring fragment (6). As the results of preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of parathyroid hormone secretion in bovine parathyroid cells and binding affinity to human recombinant vitamin D receptor and to human vitamin D binding protein in comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3-epi-1,25(OH)2D3 (3) are described.

Animals↗
PubMed2006

Beta-isocupreidine-catalyzed Baylis-Hillman reaction of chiral N-boc-alpha-amino aldehydes.

[Structure: see text] Beta-isocupreidine (beta-ICD)-catalyzed Baylis-Hillman reaction of chiral N-Boc-alpha-amino aldehydes and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) takes place without racemization and exhibits the match-mismatch relationship between the substrate and the catalyst. In the case of acyclic amino aldehydes, L-substrates show excellent syn selectivity and high reactivity in contrast to D-substrates. On the other hand, in the case of cyclic amino aldehydes, D-substrates rather than L-substrates show excellent anti selectivity and high reactivity.

Aldehydes↗
PubMed2006

A highly stereocontrolled total synthesis of (-)-neodysiherbaine A.

Neodysiherbaine A, a neuroexitotoxin occurring in a Micronesian marine sponge Dysidea herbacea, was synthesized from tri-O-acetyl-D-glucal with excellent stereocontrol. The method established enables us to obtain gram quantities of neodysiherbaine A and its related compounds.

Alanine↗
PubMed2006

Synthesis of putative metabolites of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71).

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D(3) because of metabolism at the 2beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2beta-positon and a combination of metabolism between side chain and 2beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method.

Bone Density Conservation Agents↗
PubMed2006

Prospective surveillance for atypical pathogens in children with community-acquired pneumonia in Japan.

A total of 141 children with community-acquired pneumonia (CAP) were studied prospectively to determine the causative microorganisms. Microbial investigations included examination of postnasal swabs, cultures, polymerase chain reaction (PCR), and serology. The atypical pathogens occurring most frequently were Mycoplasma pneumoniae (58 patients [41.1%]), Chlamydia pneumoniae (4 patients [2.8%]), and concurrent occurrence of both pathogens (1 patient [0.7%]). Patients aged under 4 years showed a relatively lower rate of atypical bacterial etiology compared with those aged 4 years or older. Major bacterial pathogens were detected in 89 patients (atypical pathogens were detected in 28 patients simultaneously), including Streptococcus pneumoniae in 34 patients, Haemophilus influenzae in 60, Moraxella catarrhalis in 48, and multiple pathogens in 42. In patients suspected of having atypical pneumonia, macrolides are recommended.

Adolescent↗
PubMed2005

Total synthesis of viridiofungin A.

Viridiofungin A, a member of amino alkyl citrate antibiotics from Trichoderma viride, was enantioselectively synthesized in naturally occurring form for the first time, employing regio- and stereoselective opening of the chiral glycidate with vinylmagnesium bromide and alkene cross metathesis of the citric acid core and hexadec-15-en-8-one as key steps.

Citrates↗
PubMed2004

A concise route to (+)-lactacystin.

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).

Acetylcysteine↗
PubMed2003

Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immune globulin.

UNLABELLED: A standard treatment with a dose of 2 g/kg of intravenous immune globulin (i.v.IG) is sometimes ineffective in some patients with Kawasaki disease (KD), who are commonly treated with additional i.v.IG. An interval of 6 to 7 months in Japan and 11 months in the United States is recommended before vaccination against measles after i.v.IG treatment for KD, but it is not known how long after treatment with additional i.v.IG. We studied the persistence of measles antibody titers in six episodes of KD in five patients without history of measles infection or vaccination, 4 to 28 months of age, after additional infusion of i.v.IG. The total dose was 4 g/kg in five episodes and 6 g/kg in one episode. Enzyme immunoassay antibody titers against measles were still positive (> or =400) in all patients tested 3 months after additional infusion of i.v.IG and positive in one patient and equivocal (> or =200 and <400) in three patients after 6 months, but negative (<200) in all after 9 months following infusion. Neutralization test antibody titers against measles were still positive (> or =1:4) in all patients 3 months after additional infusion of i.v.IG, but only one after 6 months, and negative (<1:4) in all after 9 months following infusion. CONCLUSION: We suggest that an appropriate interval between infusion of 4 g/kg of intravenous immune globulin and measles vaccination be 9 months. The 11-month interval recommended in the United States for 2 g/kg may be longer than necessary.

Antibodies↗
PubMed1998

Total Synthesis of (-)-Verrucarol(1).

We have achieved the total synthesis of (-)-verrucarol, a trichothecene sesquiterpenoid obtained as a hydrolysis product of the naturally occurring verrucarin A. Our total synthesis began with the previously reported enantiomerically pure bicyclic alpha-methylated gamma-lactone, which was prepared from D-glucose. The key steps for the total synthesis were (1) aldol-like carbon-carbon bond formation applied to the starting lactone using a four-carbon aldehyde as an electrophile for introduction of the quaternary stereogenic carbon sharing the B and C-rings of the trichothecene skeleton, (2) Dieckmann cyclization of the derived epsilon-ester lactone for construction of the C-ring equivalent, (3) Barton's decarboxylative oxygenation for conversion of a carboxylic acid functionality in the Dieckmann cyclization product into a hydroxyl group, (4) skeletal enlargement strategy for the crucial trichothecene skeleton construction, and (5) the final stereoselective formation of the exo-epoxy ring at the methylene carbon in the bridge constituting the B and C-rings.

Journal Article↗