Ring Rearrangement Reactions of 4-Alkenylisocoumarins and Photophysical Evaluation of Multi-Substituted Anthracene Products.

Herein we report that readily available 4-alkenylisocoumarins can be regarded as potent dienolate equivalents. For example, lactol silyl ethers derived from 4-alkenylisocoumarins were selectively converted to the corresponding benzo-homophthalates through a fluoride-induced ring opening step that was followed by a ring closure through a vinylogous intramolecular aldol condensation. Likewise, nucleophilic activation of 4-alkenylisocoumarins directly yields diversely poly-substituted naphthalenes and anthracenes without formation of any regioisomer. Photophysical evaluation of a set of thus obtained 1,3-di- and 1,3,4-trisubstituted anthracenes reveals their distinct intramolecular charge transfer (ICT) character during light absorption in polar solutions and excimer emission from the solid state when a face-to-face π-stacked molecular assembly is present in the crystal packing.

Diverse Synthesis of 2H-Isoindole-Based Polycyclic Aromatic Compounds.

1,3-Disubstituted N-aryl-2H-isoindoles have been synthesized by a cascade reaction of divinyl ethers, which are derived from easily available 4-bromoisocoumarins, with substituted anilines in HFIP. This cascade reaction consists of a ring-opening step through addition-elimination mechanism and the following 5-exo-tet type ring-closing step via the intramolecular nucleophilic substitution reaction. Thus obtained 2H-isoindoles have been derivatized to high-order nitrogen-containing polycycles including less accessible benzo[a]ullazines.

Phosphite-imidazole catalyzed N-formylation and N-acylation of amines.

A novel and convenient method for the N-formylation reaction of amines with DMF as a formylating agent has been developed, utilizing a catalytic amount of diethyl phosphite/imidazole. Diethyl phosphite, as a nucleophilic catalyst, plays a significant role in this conversion. The presented method has a broad substrate scope, and various N-formyl products were obtained in good to excellent yields. Moreover, by using DMA instead of DMF, the N-acetylation reaction was also successful. The reaction of o-phenylenediamines with DMF afforded the corresponding benzimidazoles. Furthermore, N-sulfonyl amidines were obtained in good to excellent yields by the reaction of sulfonamides with DMF under similar conditions.

Regioselective Synthesis of 4-Aryl-1,3-dihydroxy-2-naphthoates through 1,2-Aryl-Migrative Ring Rearrangement Reaction and their Photoluminescence Properties.

4-Aryl-1,3-dihydroxy-2-naphthoates having the less accessible 1,2,3,4-tetrasubstituted naphthalene scaffold and that show photoluminescence emission from solid state as well as in solutions, were selectively synthesized from brominated lactol silyl ethers through the 1,2-aryl-migrative ring rearrangement reaction.

Estrogen receptor alpha gene ESR1 amplification may predict endocrine therapy responsiveness in breast cancer patients.

Estrogen receptor (ER) alpha plays a crucial role in normal breast development and has also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients. However, the molecular mechanisms controlling the expression of ERalpha are as yet not fully understood. Gene amplification is one of the important factors regulating protein expression. Recent studies on the amplification of the ESR1 gene, which encodes ERalpha, have presented conflicting data. Using fluorescence in situ hybridization and real-time quantitative polymerase chain reaction analysis, we examined the ESR1 status in a series of breast cancer tissues and analyzed its clinical importance. ESR1 gene amplification and gain were found in 22.6 and 11.3% of samples, respectively, as determined by three-dimensional fluorescence in situ hybridization assay. Moreover, ESR1 amplification and amplification plus gain were significantly negatively correlated with tumor size, number of positive lymph nodes, negative ERalpha, and positive human epidermal growth factor receptor 2 status. It has also been shown that ESR1 amplification strongly correlates with higher expression levels of ER protein and that patients with ESR1 amplification in their tumors apparently experience longer disease-free survival than those without. Our data suggest that ESR1 amplification might prove to be helpful in selecting patients who may potentially benefit from endocrine therapy.

[Two cases of stage IV breast cancer with severe hypercalcemia].

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.

[Experience of high-dose toremifene treatment for postmenopausal women with metastatic breast cancer].

Toremifene (TOR), a selective estrogen receptor modulator (SERM), showed efficacy equivalent to Tamoxifen (TAM) in terms of the objective response rate, stable disease, time to progression and overall survival in patients with metastatic breast cancer (MBC). High-dose TOR is also effective for patients with TAM-resistant breast cancer. We tried to study retrospectively the efficacy and the safety of high-dose TOR treatment for patients with MBC in our hospital. Ten patients received TOR 120 mg daily. Most of the patients were treated with one or more endocrine agents before high-dose TOR. Objective response and clinical benefits were found in 3 patients (30%) and 7 patients (70%), respectively. Median time to progression and median overall survival were 9 months and 21.5 months, respectively. In our study,we found the efficacy for patients with hormone receptor negative, TAM resistance and aromatase inhibitor (AI)-resistance breast cancer. Adverse events induced by high-dose TOR treatment were tolerable. High-dose TOR may be one of the optional treatments for patients with MBC after TAM and AI treatment.