A quantitative structure-activity relationship for antitumor activity of long-chain phenols from Ginkgo biloba L

With the aim of obtaining compounds with strong antitumor activity, a quantitative structure-activity relationship (QSAR) of antitumor phenolic compounds (long-chain phenols) was derived using the Hansch-Fujita equation. The ED50 values against Chinese hamster V-79 cells were analyzed in terms of log P as the hydrophobic parameter and the energy of the lowest unoccupied molecular orbital (ELUMO) calculated by using the modified neglect of differential overlap (MNDO) method as the electronic parameter, by means of multiple regression analysis. It was found that the activities mainly depended on log P (an optimum log P of 8.3) and a low-lying ELUMO value. 4-Undecylcatechol, selected on the basis of the above results, exhibited strong antitumor activity against Sarcoma 180 ascites and P-388 lymphocytic leukemia.     

Study on suppressed uptake by the liver in 67Ga scintigraphy

During the past 3 years, we have performed 1525 studies of 67Ga scintigraphy and 38 cases of these showed suppressed liver uptake; 19 cases after chemotherapy, 13 cases with liver dysfunction and 6 cases with competitive blockade. Many cases in chemotherapy used cyclophosphamide and vincristine, and were performed 67Ga scan within 1 week after chemotherapy. In cases showed suppressed uptake by liver after chemotherapy, serum Fe was markedly increased and UIBC was markedly decreased (p less than 0.01). This suggested that serum Fe influenced suppressed uptake by liver more than carrier-protein, disturbed hepatic cells, and receptors.     

Synthesis and antiulcer activity of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinoli nes and related compounds

A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolin es was synthesized and examined for their (H+ + K+)adenosine triphosphatase (ATPase)-inhibitory and antisecretory activities against histamine-induced gastric acid secretion in rats. Many compounds tested were potent inhibitors of (H+ + K+)ATPase. Most compounds showed antisecretory activity. The antiulcer activity against water-immersion stress-induced gastric ulcer, aspirin-induced gastric ulcer and gastric necrosis induced by hydrochloric acid also were tested in the rat. Some of these compounds, in particular, 4-(N-allyl-N-methylamino)-1-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazoly l) sulfinylmethyl]-1-ethyl-1,2,3,4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed.     

Organic phosphorus compounds. Part 3. Synthesis of 5-fluorosubstituted benzothiazolylbenzylphosphonates

The regio specific synthesis of 5-fluorobenzothiazoles 14 has been accomplished by using difluorothiobenzanilides 13 as a key intermediate. Through this method, 5-fluorosubstituted fostedil 3 and its derivatives were synthesized and evaluated coronary vasodilator activity.     

Methyl hypofluorite (MeOF) reactions with various fluoroolefins

The reaction of methyl hypofluorite (MeOF) with certain fluoroolefins, such as CF₂CF₂, CF₂CFCF₃, CF₂CFOCF₃, CF₂CFOMe, CF₂CClF, CF₂CHF, CF₂CH₂, CHFCH₂, CF₂CFCFCF₂, occurred in CD₃CN or in the presence of NaF. Using neat MeOF in the presence of NaF was a novel method and gave good results. We observed that when more than three fluorine atoms are bonded to the CC double bond, the addition products were obtained in mostly good yields.     

Silyl-enolization-asymmetric Claisen rearrangement of 2-allyloxyindolin-3-one: enantioselective total synthesis of 3a-hydroxypyrrolo[2,3-b]indoline alkaloid alline

Asymmetric Claisen rearrangement triggered by silyl-enolization of 2-(1′-nonel-3′-yloxy)indolin-3-ones was performed in order to prepare 3-(2′-nonenyl)-3-hydroxyindolin-2-ones. Total synthesis of 3-hydroxypyrrolo[2,3-b]indoline alkaloid, (+)-alline was achieved by transformation of the allylic moiety of 3-(2′-nonenyl)-3-hydroxyindolin-2-one to amine followed by reductive cyclization.     

Reactive-state spin-dependent diastereoselective photoisomerization of trans,trans-2,3-diphenylcyclopropane-1- carboxylic acid derivatives included in zeolites

[reaction: see text] The asymmetric induction facilitated by a chiral auxiliary during the photoisomerization of trans,trans-2,3-diphenylcyclopropane derivatives depends on the medium (solution vs zeolite) and the reactive state (singlet vs triplet). Within zeolites, direct excitation most likely proceeds via a zwitterionic intermediate, while triplet sensitization most likely proceeds via a diradical intermediate.     

Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas.

The hot water extracts of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas, were found to have potent inhibitory activity towards lens aldose reductase (AR). Ellagic acid (4) was isolated from C. morifolium and I. batatas, isoscutellarein (7) from B. orellana and 3,5-dicaffeoylquinic acid (10) from I. batatas, respectively, as potent inhibitors.     

Transformation of the Iboga alkaloid voacangine into voaketone, a derivative of beta-carboline (author's transl)]

Transformation of the Iboga alkaloid voacangine into voaketone, a derivative of β-carboline. The reduction product voacanginol ( 2 ), obtained from the indole alkaloid (?)-voacangine ( 1 ), gave, by treatment of its tosylate 3 with methanolic pyridine in the presence of air, the rearrangement product (?)- 5 (voaketone). Its structure was derived from spectroscopic evidence (mainly NMR. and mass spectra) and some chemical transformation reaction, especially deuterium labelling. A possible mechanism for the formation of 5 from 3 is given in Scheme 6. The absolute configuration of 5 was deduced by comparison with yohimbine derivatives.     

The unique properties observed for the unsymmetrical macrocyclic compounds with the highly distorted structure

A new class of aza-macrocycles with the highly distorted structure was found to exhibit unique properties. These macrocycles react with various lithium salts to form lithium complexes and their lithium complexation reactions depend on a substituent on the macrocyclic ring; slower rates and larger equilibrium constants were observed for the macrocycle with a bulkier substituent. The irradiation of these macrocycles by UV light was found to lead to the isomerization, and the photoisomerization rate of macrocycle with the bulky substituent was much faster. The highly distorted structure of these macrocycles makes it much easier to change the conformation of macrocyclic skeleton and these macrocycles have a variety of conformations. The factors to govern this conformational change were therefore explored. The solvent effect was examined by ¹H NMR spectroscopy, because these macrocycles have a strong intramolecular hydrogen bond in the ring. As a result, the solvent was found to have a big effect on the ¹H NMR spectra of macrocycles that could be explained in terms of the conformational change of macrocycle. This finding suggests the solvent to be an important way of controlling the conformation.