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At least 127 records · Page 7Linked to original sources
PubMed2006

N-heterocyclic carbene catalyzed reaction of enals and 1,2-dicarbonyl compounds: stereoselective synthesis of spiro gamma-butyrolactones.

[reaction: see text]. Nucleophilic heterocyclic carbene (NHC) catalyzed annulation of enals and cyclic 1,2-dicarbonyl compounds, opening a route to gamma-spirolactones, has been observed for the first time. The strategy works well with isatins, leading to spiroannulated oxindole derivatives. It is conceivable that the spiroannulation protocol reported herein will be applicable to the synthesis of important natural products that are endowed with a spiro gamma-butyrolactone motif, especially oxindoles and norsesquiterpenoids.

4-Butyrolactone↗
PubMed1984

A Phase I trial of spirogermanium administered on a continuous infusion schedule.

We have evaluated the toxicity of the antitumor agent spirogermanium on a schedule of continuous intravenous administration for periods up to five days. The doses tested were between 100 mg/m2/day and 500 mg/m2/day. Peripheral vein phlebitis occurred at all dose levels and was not relieved by addition of hydrocortisone or heparin to the infusion. No phlebitis occurred when the drug was administered through a central vein. The dose limiting toxicity of spirogermanium was neurologic, notably tremors and mental confusion. These problems became progressively more severe at doses above 250 mg/m2/day. There was no discernible bone marrow, renal or hepatic toxicity. One patient developed reversible interstitial pneumonitis. The recommended Phase II dose of spirogermanium is 200 mg/m2/day for five days, with the possibility of escalation in selected patients. Because spirogermanium is more toxic to tumor cells with prolonged exposure than with intermittent exposure, this schedule could be considered for Phase II trials, particularly in diseases thought to be especially sensitive such as ovarian and prostatic carcinoma or lymphomas.

Adult↗
PubMed1985

A phase II study of spirogermanium as second line therapy in patients with poor prognosis lymphoma. An NCI Canada Clinical Trials Group Study.

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of spirogermanium given daily for 5 days every 3 weeks to patients with poor prognosis non-Hodgkin's lymphomas. All patients had had a maximum of one prior treatment regimen. No responses were seen in 13 evaluable patients. Toxicity was primarily neurologic and mild or moderate in most patients. There is no evidence of activity of spirogermanium given in this schedule in this subset of lymphoma patients.

Aged↗
PubMed1989

Inhibition of autoimmune disease and the generation of suppressor cells by spirogermanium: a biological profile similar to total lymphoid irradiation.

Oral administration of spirogermanium (Sg), inhibits the development of immune-mediated hindpaw inflammation in the rat model of adjuvant arthritis (AA) and DTH responses to PPD (30 mg/kg/day). A similar dosing protocol inhibits hindleg paralysis in experimental autoimmune encephalomyelitis (EAE). The spleens of these animals and those of normal rats contain radiation resistant (2000 R) non-specific suppressor cells (SC) which bear some similarity to those generated following total lymphoid irradiation (TLI). These cells do not appear to be mature T cells, they are partially adherent to plastic, sephadex G10 and nylon wool, insensitive to indomethacin and are enriched in a 1.07 g/ml fraction of a Percoll density gradient.

Animals↗
PubMed1987

Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs.

We compared the in vitro growth inhibition of primary human tumor cells in the adhesive tumor cell culture system (ATCCS), exposed to the investigational agents caracemide, spirogermanium and taxol and to standard chemotherapy agents at equitoxic concentrations for granulocyte-macrophage colony-forming cells (GM-CFC) in vitro. Clinically active standard agents tested at up to GM-CFC 90% inhibitory concentrations (IC90) resulted in in vitro activity (greater than or equal to 50% tumor growth inhibition) in at least 30% of tumors tested. In vitro responses for taxol, caracemide and spirogermanium were 78%, 9% and 7%, respectively. This paper proposes a model that incorporates two hypotheses: (1) myelotoxic drugs which inhibit tumor growth at concentrations equal to or less than equitoxic GM-CFC ICs will demonstrate clinical activity; and (2) both myelotoxic and particular nonmyelotoxic drugs inactive in vitro at these doses will not be active clinically. If this drug screening concept is valid, taxol may be clinically more active than caracemide and spirogermanium.

Alkaloids↗
PubMed2006

Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory.

Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE epsilon4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition-memory performance between AD-symptom-free carriers (N=30) and non-carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE epsilon4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE epsilon4 carriers made significantly more false alarms in the recognition-memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

Age Factors↗
PubMedDate not supplied

Controlled synthesis of star-shaped L-lactide polymers using new spirocyclic tin initiators.

The reaction between pentaerythritol ethoxylate compounds and dibutyltin oxide was developed as a route to synthesize two new spirocyclic tin initiators. The initiators were successfully synthesized and they were characterized by (1)H NMR and differential scanning calorimetry (DSC). The (1)H NMR spectra showed the characteristic signals for the methylene protons in the ether chains. Furthermore, the usefulness of the new initiators was examined in ring-opening polymerizations of L-lactide in chloroform at 60 degrees C. L-Lactide was polymerized at monomer-to-initiator ([M]/[I]) ratios between 20 and 500. The results indicated that the initiation was instantaneous and that the molecular weight distribution was very narrow, <1.13. The number average molecular weight could be controlled by the [M]/[I] ratio, and the yield was very high. (1)H NMR, size exclusion chromatography, and DSC were used to clarify the architecture. The expected results were obtained. The star-shaped polymers had a smaller hydrodynamic volume, and the melting point was lower than that obtained for the corresponding linear poly(L-lactide).

Biocompatible Materials↗
PubMed2002

Enhancement of enantioselectivity by THF in asymmetric mo-catalyzed olefin metathesis. Catalytic enantioselective synthesis of cyclic tertiary ethers and spirocycles.

Mo-catalyzed enantioselective rearrangement of achiral cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers are reported. These olefin metathesis transformations proceed efficiently and with high levels of enantioselectivity. A noteworthy feature of these reactions is that added tetrahydrofuran exerts a remarkably positive influence on the enantioselectivity of the metathesis-based rearrangement. The first examples of catalytic asymmetric synthesis of spirocyclic structures by enantioselective olefin metathesis are also disclosed.

Alkenes↗
PubMed2004

Spirodiepoxides in total synthesis: epoxomicin.

The first use of the spirodiepoxide functional group in total synthesis, a study culminating in an efficient synthesis of the potent proteasome inhibitor epoxomicin, is described. Spirodiepoxides derived from allenes by oxidation are shown to give syn disubstituted ketones and their derivatives, including ortho ester, oxazoline, azido epoxide, as well as sulfonamide-, amide-, and azide-containing hydroxy ketones.

Epoxy Compounds↗
PubMed2003

First total synthesis of (-)-AL-2.

Treatment of the 3,4-dioxygenated-9-hydroxy-1-nonyn-5-one derivative, derived from diethyl l-tartrate, with a palladium catalyst in methanol under a CO atmosphere effected an intramolecular acetalization and a stereoselective construction of the (E)-methoxycarbonylmethylidene functionality resulting in formation of the core framework of the diacetylenic spiroacetal enol ether natural products. Chemical transformations of the 1,6-dioxaspiro[4.5]decane derivative thus formed led to the first total synthesis of (-)-AL-2. [reaction: see text]

Acetals↗
PubMed2004

A concise asymmetric synthesis of the ADE fragment of nakadomarin A.

The ADE fragment of nakadomarin A has been synthesized in nine linear steps from commercial material. The key transformation is an asymmetric azomethine ylide [1,3]-dipolar cycloaddition to establish the AD-spirocyclic system containing three of the four stereocenters of the natural product. [reaction: see text]

Azo Compounds↗
PubMed1993

Efficacy of azithromycin for treating Babesia microti infection in the hamster model.

Because of its prevalence and severity, Babesia microti infection is an important public health problem. The current treatment of choice is clindamycin plus quinine. However, in some cases other treatments are needed because of drug intolerance or relapse. The activity of azithromycin was investigated for treatment of babesiosis in the hamster model. All animals received vancomycin to prevent antibiotic-associated colitis. Quinine (250 mg/kg/day), azithromycin (150 mg/kg/day), and the combination of azithromycin and quinine were compared. A significant suppression of parasitemia was found in all treatment groups (combination had the greatest effect, followed by azithromycin, then quinine; P < .05). The mean survival was significantly prolonged in the combination group (P < .05). Azithromycin as monotherapy in a higher dose (300 mg/kg/day) also resulted in a significant prolongation of survival (P < .05). Spirogermanium and ciprofloxacin, which have been reported to have antimalarial activity, had no effect on parasitemia or survival in this experimental babesiosis model.

Animals↗