(+)-Biotin (1) was synthesized from readily accessible L-aspartic acid (4). The contiguous asymmetric centers at C-3a and C-6a were formed through a diastereoselective aldol reaction of N-Cbz-3-amino-4-butanolide 5 to provide trans-disubstituted lactone 6 with high stereoselectivity (trans/cis=12 : 1). The imidazolidin-2-one moiety of 1 was constructed by a stereoselective Hofmann rearrangement of β-substituted asparagine derivative 7 to provide cyclic urea 8. This reaction proceeds with complete retention of stereochemistry. Removal of the protective groups of 8 and subsequent dibenzylation and thionation provided thiolactone 2. The installation of the C-4 side chain of 1 was performed through a Pd/C-catalyzed coupling reaction of 2 with ethoxycarbonylbutylzinc iodide 14a (Fukuyama coupling reaction), which permitted the synthesis of 1 from 2 under industrially applicable mild conditions in three steps.
Natural products have been used for healthcare and pharmacotherapy. Because difficulties in quality control affect their production, processing, and marketing, it is necessary to establish adequate marker compounds for their effective application. Ergosta-4,6,8(14),22-tetraen-3-one(I) was studied in the screening of the marker compounds for the standardization of Polyporus Sclerotium (ChoRei), which has the advantage of easy qualitative and quantitative analysis because of its fluorescence. Its applicability in the standardization of Polyporus Sclerotium is discussed based on comparative studies of 30 crude samples of Polyporus Sclerotium and some other fungi herbs using TLC and HPLC analysis with I it as the marker compound, as well as its chemical synthesis.
Cervical radiation therapy is often applied to patients with head and neck cancers because radiation has a high sensitivity to these cancers and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. We have encountered some patients who showed hypercholesterolemia resulting from cervical radiation. Therefore, we have paid close attention to the relationship between hypercholesterolemia after cervical radiation and hypothyroidism. Thyroid hormone tests in these patients with hypercholesterolemia after cervical radiation showed high thyroid stimulating hormone (TSH) and low free thyroxine (fT4), indicating the presence of hypothyroidism. After administration of levothyroxine Na, their fT4 levels increased and both TSH levels and serum total cholesterol levels decreased. In conclusion, in patients who have received cervical radiation, we recommend monitoring serum total cholesterol periodically to detect hypothyroidism easily before the appearance of its symptoms.
We placed a “drug information card” on each medication shelf to assist dispensing by pharmacists, education of students, and risk management of pharmaceutical practices at the Department of Pharmacy, University of Tokyo Hospital. To provide appropriate information items on the drug information cards, we conducted questionnaire survey of 41 pharmacists on the utility of the cards and reviewed questions received from medical staff in the drug information section in our hospital. Based on the results of these investigations, “usage and dosage,” “interactions,” “contraindications,” “product name,” and “effects” were printed as basic information items on the drug information cards. Furthermore, information on pharmacokinetics was added. To make maintenance easier, we classified drug information items into “renew often” and “not so often.” A good response on the use of the drug information cards was received for dispensing support from 38 pharmacists (92.7%), 14 trainees (100%), and 16 students (94.1%) in the questionnaire investigation. The drug information cards make it possible to obtain precise information rapidly in pharmacies.