Effect of cyclodextrins on the stability of adriamycin, adriamycinol, adriamycinone and daunomycin

The stability of adriamycin (ADR), adriamycinol, adriamycinone (ADR-ONE) and daunomycin in the presence of alpha-, beta- and gamma-cyclodextrins (CDs) was studied using high-performance liquid chromatography. It was found that alpha-CD did not affect the degradation of tested compounds, beta-CD caused a little effect and gamma-CD resulted in pronounced stabilizing effect. The formation of complexes between ADR and ADR-ONE with CDs was monitored by fluorescence spectroscopy. The fluorescence spectrum of ADR-gamma-CD complex had an activation maximum at 460 nm, emission maximum at 555 nm and a shoulder at 585 nm. A similar finding was observed in case of alpha-CD. In case of beta-CD, the fluorescence intensity at 580 nm peak enhanced less than in case of gamma-CD. With ADR-ONE, alpha-CD did not cause any significant change compared with the spectrum of free molecule. On the other hand, it was noticed that, the fluorescence spectra of ADR-ONE with both beta- and gamma-CD were the same but showed a significant difference to the spectrum of free molecule, especially the molar fluorescence of the 585 nm emission peak.     

Catalyst-controlled asymmetric synthesis of fostriecin and 8-epi-fostriecin

Catalytic asymmetric synthesis of the natural antibiotic fostriecin (CI-920) and its analogue 8-epi-fostriecin and evaluation of their biological activity are described. We used four catalytic asymmetric reactions to construct all of the chiral centers of fostriecin and 8-epi-fostriecin; cyanosilylation of a ketone, Yamamoto allylation, direct aldol reaction, and Noyori reduction, two of which were developed by our group. Catalytic enantioselective cyanosilylation of ketone 13 produced the chiral tetrasubstituted carbon at C-8. Both enantiomers of the product cyanohydrin were obtained with high enantioselectivity by switching the center metal of the catalyst from titanium to gadolinium. Yamamoto allylation constructed the C-5 chiral carbon in the alpha,beta-unsaturated lactone moiety. A direct catalytic asymmetric aldol reaction of an alkynyl ketone using LLB catalyst constructed the chirality at C-9 with the introduction of a synthetically versatile alkyne moiety, which was later converted to cis-vinyl iodide, the substrate for the subsequent Stille coupling for the triene synthesis. Noyori reduction produced the secondary alcohol at C-11 from the acetylene ketone 6 with excellent selectivity. Importantly, all the stereocenters were constructed under catalyst control in this synthesis. This strategy should be useful for rapid synthesis of stereoisomers of fostriecin.     

Syntheses and bioactivities of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines

A number of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones have been synthesized and their anticancer and antimalarial activities evaluated. A one-pot synthesis of 2,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione (4) was achieved by heating a mixture of 1,4-dimethoxyanthracene, methoxyhydroquinone, silver oxide, and zinc iodide in toluene. Regioselective bromination of 4 and 2-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (7) with N-bromosuccinimide provided 2-bromo-3,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione and 2-bromo-3-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (1), respectively. The reactions of 1 with aliphatic primary amines and secondary amines, respectively, produced different products, a result most likely attributed to the different basicities (or nucleophilicities) and steric effects of the two kinds of amines. The structure of the displacement product, 2-bromo-3-[2-(tert-butoxycarbonyl)ethylamino]-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone, from the reaction of 1 with tert-butyl 3-aminopropanoate was unequivocally determined by a single-crystal X-ray analysis. IC(50) values of triptycene bisquinones for the inhibition of L1210 leukemia cell viability are in the 0.11-0.27 microM range and for the inhibition of Plasmodium falciparum 3D7 are in the 4.7-8.0 microM range.     

X-ray crystallographic studies and molecular calculations on 1∶1 inclusion complexes of cholic acid with acetophenone and its derivatives

Molecular calculations were applied to four channel-type inclusion complexes of cholic acid (CA) with acetophenone or its derivatives (3-, 4-fluoroacetophenone and 2-chloroacetophenone). According to the calculated results, both the total and van der Waals interaction energies between channel and included guests depend on the channel form determined by the guest species. Similarly, the channel form is responsible for the dipole moment of the channel. Further examination of the results suggests that dipole-dipole interaction does not play an important role in the determination of the guest orientation. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82193 (26 pages).     

Fabrication and low threshold current density CW operation of GaInAsP/InP multiple-reflector microcavity laser

We report CW operation of a GaInAsP/InP multiple-reflector microcavity (MRMC) laser operated at fairly low threshold current density. The threshold current density with broad contact (stripe widthW=240 m, cavity lengthL=60 m) under pulsed operation was 180 A cm^–2 (l _th=20 mA), and was 230 A cm^–2 under CW operation at room temperature operating at 1.52 m wavelength.     

Double-lambda compound nucleus and the formation of double hypernuclei

The formation probabilities of single- and double- compound nuclei from ^– following the (K^–, K⁺) reaction are calculated, showing that double- hypernuclei are formed with a fairly large probability through a hyperon compound process involving ^– directly after the (K^–, K⁺) reaction.We dedicate this paper to the late Professor Jan ofka with whom we enjoyed nice friendship and collaboration. We also thank the late Professor H. Bando and Professors K. Yazaki, Y. Akaishi and T. Fukuda for stimulating discussions.