Synthesis of Galactosylhydroxylysine and its Analogs

Synthesis of (--)-galactosylhydroxylysine (GHL, I), and its analogs (+)-2 and (+)-3, which are essential for development of assays for osteoporosis, is described starting from (2S,5R)-(+)-hydroxylysine (4).     

An experimental study towards micro-mechanical modeling of fiber-reinforced aerogels

Fiber-reinforced aerogels are a class of reinforced aerogels characterized by very low thermal conductivity, hydrophobicity and most importantly load bearing capability. In this work, an experimental study describing the damage in these fiber-reinforced aerogels through various uniaxial compression tests is presented. While understanding the damage evolution at the micro-scale, we come across three probable sources contributing towards the damage evolution. They are: (a) matrix cracks, (b) debonding of particles due to fiber sliding, and (c) breakage of fibers. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Microwave assisted sulfopropylation of N-heterocycles using 1,3-propane sultone

Dramatic rate acceleration was observed for N-sulfopropylation of heterocyclic compounds (1a-h) using 1,3-propane sultone(2) under microwave irradiation affording the N-sulfopropylated compounds (3a-h) in 68–95% yield.     

Elasticity of adsorbent beds

The practical application of adsorbents with the desired separation properties depends not only upon the adsorption characteristics of the material but also upon the mechanical properties of the packed bed. The packed bed, the vessel surrounding the bed and any internal structure that supports the bed are subjected to both static and cyclic loads during an adsorption process. In order to properly design the vessel and its internal structure, the bulk mechanical properties (most particularly the elastic properties) of the adsorbent bed must be known. The primary focus of this study was to determine the elastic properties of adsorbent beds packed with activated alumina, synthetic molecular sieve 13X or natural zeolite clinoptilolite. The bulk modulus of elasticity was found to be a linear function of applied stress for each of these materials in a range of stresses lower than the bulk crush strength. The Poisson’s ratio for the packed bed was also deduced from these results.     

Application of vicarious nucleophilic substitution to the total synthesis of dl-physostigmine

A concise, highly efficient formal total synthesis of dl-physostigmine is described, using a relatively simple method that should be adaptable to the synthesis of homologous members of this type of alkaloid. The key step in the synthesis is a new vicarious nucleophilic substitution reaction between p-nitroanisole and a C-silylated derivative of N-methylpyrrolidinone. Subsequent conversion of the initial adduct to the tricyclic framework of physostigmine follows a well-established protocol and provides the key intermediate 8 in high yield. The vicarious nucleophilic substitution reaction has also been extended to six-membered lactams, with encouraging results.     

Development of a rapid and sensitive high-performance liquid chromatographic method to determine CYP2D6 phenotype in human liver microsomes

Dextromethorphan is a probe substrate to determine CYP2D6 phenotype. The conversion of dextromethorphan to dextrorphan by CYP2D6 accounts for approximately 60% of total metabolism. Most analytical methods utilize complicated labor- and time-intensive sample processing methods with several liquid-liquid extraction (LLE) steps. Our goal was to develop a non-LLE based rapid and sensitive HPLC method, to measure dextromethorphan metabolism in human liver microsomes. A solid-phase filtration based reverse-phase HPLC method with fluorescence detection was developed and validated. Human liver (n = 6) microsomal incubations were carried out with dextromethorphan, under optimum conditions. The analytes were separated by one-step centrifugal filtration with Nanosep separation units. The filtrate was injected ( 50 microL) into a Waters Alliance 2690 HPLC system. Metabolic incubations were also conducted to determine levels using LLE for comparisons. The Nanosep separation step reduced the extraction time from 3h to 40 min. The limit of quantitation was 23.8 nM (9.7 ng/mL), recovery was approximately 98%, the mean precision values were <10% RSD for the controls (80, 320 and 640 nM) and mean percentage error was <5%. Michaelis-Menten parameters were determined to distinguish CYP2D6 phenotypes. A rapid and sensitive HPLC method is reported, which may be suitable for automation and allows phenotyping of human liver microsomes.