In the course of our search for new antitumor agents in breast cancer, novel amino-substituted flavone derivatives were synthesized and examined for antitumor activities. Among them, 5,4'-diaminoflavone and some of its congeners showed remarkable antiproliferative activity against the estrogen receptor (ER)-positive and estrogen-responsive human breast cancer cell line MCF-7. The activity was observed irrespective of the presence or absence of estrogen. The 5-aminoflavone derivatives (5-AFs) are not classical anti-estrogens because they did not compete with [3H]estradiol to bind the estrogen receptor. Moreover, 5-AFs showed antitumor activity highly selective to the ER-positive breast cancer cell line, and they showed no effects against the ER-negative human cancer cell lines HeLa S3, WiDr, and MDA-MB-453. Although the mechanism of their selective antitumor activity to ER-positive breast cancer cells is unclear, 5-AFs are expected to be a new type of antitumor agents in breast cancer.

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A large-scale manufacturing method of l-alanyl-l-glutamine used for a component of parenteral nutrition has been studied. The method consisted of a reaction of d-2-chloro- or d-2-bromopropionic acid with thionyl chloride and Schotten−Baumann reaction with l-glutamine followed by ammonolysis reaction. The intermediate d-2-chloropropionyl-l-glutamine was found to be more stable than its bromo analogue. In the ammonolysis reaction, the former intermediate needed a higher reaction temperature, but the by-products produced had little effect on the quality of the final product. The structures of the by-products were conjectured mainly by mass spectrometry and they were removed by anion resin treatment and recrystallization.

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