A new synthesis of chlorins.
A new synthesis of chlorins has been developed, based upon the acid-catalyzed condensation of dialdehydes AB with dipyrromethanes CD.
Aldehydes↗
Biomedical subjects
S H Leung
Publications and source records attributed to S H Leung.
Cefepime versus vancomycin plus netilmicin therapy for continuous ambulatory peritoneal dialysis-associated peritonitis.
Cefepime is a cephalosporin with a broad spectrum of activity against most gram-positive and gram-negative pathogens. In this study, we attempted to compare the safety and efficacy of cefepime monotherapy against the potentially more toxic combination of vancomycin and netilmicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated bacterial peritonitis. Eighty-one consecutive CAPD patients who presented with peritonitis from January 1, 1998, to June 30, 2000, were recruited for study. Patients were randomized to be administered either intraperitoneal (IP) cefepime, 1 g once daily (group A), or intravenous vancomycin and netilmicin at conventional doses (group B) for 10 days. Bacterial growth was obtained in 52 episodes (66%), and pathogens identified included gram-positive organisms (30 episodes; 38%), gram-negative organisms (14 episodes; 18%), mixed organisms (2 episodes; 2.5%), and fungus (6 episodes; 8%). Eight patients were excluded after randomization for various reasons (6 patients, fungal peritonitis; 2 patients, wrong diagnoses). Because of the relatively low peritonitis rate after the use of a disconnect system, the sample size of this study was relatively small, giving a power of 0.45. There were no significant differences in primary response rates and cure rates (no relapse >28 days after completion of antibiotic therapy) between both groups of patients (group A versus group B, 82% [32 of 39 patients] versus 85% [29 of 34 patients] and 72% [28 of 39 patients] versus 76% [26 of 34 patients], respectively; P = not significant). No significant side effect was encountered in either group. Total peritonitis-related hospitalizations were 84 patient-days (1, 7, 8, 11, 20, and 37 patient-days) and 115 patient-days (3, 6, 9, 14, 21, 21, and 41 patient-days), whereas total costs per patient cure were estimated to be US $1,039 and US $1,371 in groups A and B, respectively. We conclude that once-daily 1-g IP cefepime monotherapy is a simple, safe, and cost-effective alternative to vancomycin and netilmicin therapy in the treatment of CAPD-associated bacterial peritonitis.
Adult↗
New syntheses of the C,D-ring pyrromethenones of phytochrome and phycocyanin.
Pyrromethenone 7, the C,D-ring segment of phytochrome (Pr, 4), has been prepared in an efficient fashion employing three new strategies. Each of these has potential advantages for the synthesis of labeled material. Our first approach is related to the Gossauer synthesis, with the difference that strong alkali is avoided in the condensation of the C- and D-ring components 8 and 17. The key silyloxypyrrole 17 was readily prepared on multigram scales beginning with inexpensive butyrolactone (10). A second synthesis began with 2-acetylbutyrolactone (41). The key steps involved conversion of 41 to the Z-enoltriflate 42, followed by Pd(0)-catalyzed coupling with trimethylsilylacetylene, p-chlorophenylselenide ring opening, and finally, amidation to afford the ring-D synthon 45 having the proper geometry and oxidation state for conversion to 7. Sonogashira coupling of 45 with the iodopyrrole 22, followed by oxidative elimination, and F(-)-induced 5-exo-dig cyclization of the resultant pyrroloalkyne 47, then completed the synthesis. In similar fashion, we have also prepared pyrromethenone 6, the C,D-ring segment of phycocyanin (2).
Magnetic Resonance Spectroscopy↗
New strategies for the synthesis of biologically important tetrapyrroles. The "B,C + D + A" approach to linear tetrapyrroles.
Linear tetrapyrroles related to phytochrome (1) were prepared in enantiospecific fashion by a new strategy beginning with ring-B,C synthons of type 19 (bis-iododipyrrins). Rings A and D were elaborated by Pd(0)-mediated coupling of 19a with the appropriate alkyne acid or amide derivatives 9 and 20, followed by intramolecular cyclization (method C: BC + D + A --> ABCD).
Magnetic Resonance Spectroscopy↗
Polyanionic hydrogel as a gastric retentive system.
Gastric emptying of a polyanionic hydrogel, polycarbophil (PC), from the canine stomach was studied using a duodenal cannulation technique. The basis of the study is to employ a certain quantity of swelling hydrogel that, by virtue of its swollen size and viscosity, converts a fasted stomach to a fed state and resists discharge from the stomach for an extended period of time. Different amounts of PC, in 200 ml water plus buffering agents, were administered orally to fasted canines. The gastric emptying lag time was found to increase with the viscosity of the administered dose. Addition of a base, sodium bicarbonate, to PC increased gastric retention via an increase in its apparent viscosity. The polymer mass is retained in the canine stomach until a sufficient quantity of stomach acid secretion reduces the viscosity of the viscous mass, through protonation of polycarbophil, and, at that point, discharge of the hydrogel will commence. Thus, gastric retention of PC hydrogel in the canine stomach can be prolonged by increasing the apparent viscosity of the hydrogel administered.
Acrylic Resins↗
Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships.
Bioadhesion, and more specifically mucoadhesion, is becoming an important strategy for drug delivery. As a result, it is important to understand the various mechanisms that govern attachment of polymeric substances to the glycoproteins on epithelial surfaces, along with the associated structure-activity relationships of the polymer. This article reviews fundamentals of mucoadhesion, with special emphasis on structural features of the polymer as they contribute to the process of mucoadhesion. There are four possible general interactions between mucoadhesive polymers and glycoproteins: (1) covalent attachment; (2) electrostatic interaction, which requires matching of charge groups between the polymer and mucus; (3) hydrogen bonding; and (4) hydrophobic interactions. Aside from covalent attachment, which is not presently a prominent mechanism for mucoadhesion, the remaining mechanisms require maximum contact between the polymer and mucin for optimum adhesion. With polyelectrolyte polymers, the charged groups are important in controlling the degree of hydration of both the polymer and the mucous network. The expanded nature of the swollen polymer and mucus enhances the interdiffusion process and permits both a mechanical entanglement and an increase in surface contact for hydrogen bonding and/or electrostatic interaction between the polymer and the mucous network. A number of techniques are available to study mucoadhesion. Some of these are better suited to study the kinetics of the mucoadhesion process whereas others are more useful for equilibrium studies. To date, the major deficiency in basic studies of mucoadhesion is the lack of suitable information on the organization and physicochemical properties of the mucin layer.
Acrylates↗