Total synthesis of Amaryllidaceae alkaloids, (+)-vittatine and (+)-haemanthamine, starting from d-glucose

The stereoselective total synthesis of (+)-vittatine 1 and (+)-haemanthamine 2 starting from d-glucose is described. The cyclohexene ring in 1 was prepared in an optically active form from d-glucose using Ferrier's carbocyclization reaction, and the critical quaternary carbon was stereoselectively generated via chirality transfer by the Claisen rearrangement of cyclohexenol 6. The hexahydroindole skeleton was effectively constructed by the intramolecular aminomercuration-demercuration of 14, followed by Chugaev reaction to provide 16. Finally, Pictet-Spengler reaction completed the first chiral synthesis of (+)-vittatine 1. On the other hand, the α-hydroxylation of the ester 5 stereoselectively proceeded to give α-hydroxy ester 19, to which was introduced an amino function to provide 4. A similar transformation of 4, as employed in the synthesis of vittatine, furnished (+)-haemanthamine 2.     

Amphotericin B covalent dimers with carbonyl-amino linkage: a new probe for investigating ion channel assemblies

Based on an amphotericin B (AmB) ion-channel model where the close proximity of neighboring molecules is effected by interaction between carboxyl and amino groups, we prepared covalent dimers of AmB connected between these functionalities. While directly connected and short-tethered derivatives (2 and 3) lacked the activities, dimer 4 with a longer linker revealed K⁺ ion flux activity, suggesting that some distance and/or flexibility between the carboxyl and amino groups in adjacent molecules is required for the formation of ion-permeable complex in biomembranes.     

Preferential intramolecular ring closure of aminoalcohols with diethyl carbonate to oxazolidinones

The closure by cyclization with diethyl carbonate (EtO)(2)CO from aminoalcohols 1 as starting material can lead to the oxazolidinones 2a, b and 2c, respectively. In the reaction of trans-isomer (6) and (EtO)(2)CO, isolated products were also only 5-membered oxazolidinone derivative (7), containing its dehydrated derivative 8. The preferential formation of the 5-membered oxazolidinone ring system apparently indicated that this process (5-Exo-Trig ring closure) is more favorable than that of 6- or 7-membered ring derivative (3 or 9) by 6- or 7-Exo-Trig ring closure.     

Synthesis of hybrid resins via polysiloxane with methacryloyloxy groups

A polysiloxane derivative with methacryloyloxy groups (MPS) that was obtained from the reaction of polymeric tributylstannyl ester of silicic acid and (3‐methacryloyloxypropyl)dimethylchlorosilane was demonstrated to be a useful inorganic component for the preparation of organic–inorganic hybrid resins as nanocomposites. The copolymerizations of MPS with common monomers such as styrene, acrylonitrile, and methyl methacrylate proceeded readily at room temperature under UV irradiation to give the corresponding resins in good yields. The resins obtained from MPS and methyl methacrylate showed good transparency, hardness in a scratch test, and resistance to toluene but had poor flexibility. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1–7, 2001     

Asymmetric anionic polymerization of maleimides bearing bulky substituents

Asymmetric anionic homopolymerizations of N‐substituted maleimide (RMI) bearing bulky substituents [R = benzyl, diphenylmethyl (DPhMI), 9‐fluorenyl (9‐FlMI), triphenylmethyl, (diphenylmethyloxycarbonyl)methyl, (9‐fluorenyloxycarbonyl)methyl] were carried out with complexes of organometal compounds (alkyllithium, diethylzinc) with six chiral ligands to obtain optically active polymers. The chiroptical properties of the polymers were affected strongly by the substituents on nitrogen in the maleimide ring, the organometal and chiral ligands. Poly(DPhMI) initiated by an n‐butyllithium/(−)‐sparteine (Sp) complex showed a positive specific rotation ([α] +60.3°). Poly(9‐FlMI) prepared with a florenyllithium/Sp complex exhibited the highest specific rotation (+65.7°). The specific rotations of the poly(RMI) obtained were attributed to different contents between the stereogenic centers (S,S) and (R,R) based on threo‐diisotactic structures of the main chain. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 310–320, 2000     

Cover Picture

The cover picture shows how protein matrices can regulate the spatial arrangement and orientation of a heme-based donor (Zn-heme: ZnPP)-sensitizer (Ru²⁺(bpy)₃)-acceptor (cyclic viologen: BXV⁴⁺) triad. A U-shape conformation of the triad without protein matrix changes into a triangle arrangement by incorporation into apocytochrome b₅₆₂ (Cyt-b₅₆₂), or into a further extended conformation by apomyoglobin (Mb) matrix. The electron transfer pathways and the lifetimes of the photoinduced charge-separated states were remarkably affected by the protein wrapping effect.     

SPECTRAL ANALYSIS OF CHLOROPHYLL a AGGREGATES IN THE PRESENCE OF WATER-SOLUBLE MACROMOLECULES

Abstract— The absorption and fluorescence spectra of chlorophyll a (Chi a) aggregates formed in aqueous solutions of polyvinyl alcohol) (PVA), polyvinyl pyrrolidone) (PVP), and bovine serum albumin (BSA) were analyzed by curve-fitting methods in the wavelength region from 650 to 800 nm. The results indicated that the aggregation of Chi a to polymeric forms such as (Chia–2H₂0), was suppressed in the presence of the macromolecules. The suppression was due to a coordination of macromolecule bound ligands to Chi a and was strongest in BSA and weaker in PVA. There were differences in the spectra even though the same types of polymeric Chi a forms were observed due to characteristically different composition of these forms. Fluorescence patterns indicated that energy was transferred from the shorter to the longer wavelength forms.     

siRNA-mediated Knockdown of the Heme Synthesis and Degradation Pathways: Modulation of Treatment Effect of 5-Aminolevulinic Acid-based Photodynamic Therapy in Urothelial Cancer Cell Lines

Photodynamic therapy mediated by 5-aminolevulinic acid (ALA-PDT) has been developed as a therapeutic modality for refractory superficial bladder cancers. Here, in experiments using urothelial cancer cell lines, we investigated the effects of siRNA modulating heme-synthetic and degradation pathways for ALA-PDT. Targeted knockdown of ferrochelatase (FECH) suppressed heme synthesis and significantly increased intracellular protoporphyrin IX (PpIX) accumulation, leading to enhanced phototoxicity in four of five cell lines. Heme oxygenase-1 (HO-1) is recognized as important for cytoprotection against oxidative stress such as PDT. Targeted knockdown of HO-1 leads to decreased intracellular PpIX accumulation, resulting in a failure to enhance ALA-PDT effect in four cell lines. Knockdown of HO-1 caused marked growth inhibition in UM-UC-2 overexpressing HO-1, whereas no inhibitory effect was observed in UM-UC-3 lacking HO-1 expression. Moreover, HO-1 protein levels and (GT) _n repeat polymorphism of the HO-1 gene promoter region were examined with the implication that the constitutive expressions of HO-1 protein were associated with a shorter (GT) _n repeat. Our results suggested that (1) FECH siRNA improved the phototoxicity of ALA-PDT, (2) overexpression of HO-1 was associated with shorter (GT) _n repeat of the promoter region, and (3) siRNA-mediated knockdown of HO-1 could suppress the growth of bladder cancer cells overexpressing HO-1.