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21.
[reaction: see text] A practical synthesis of the potent class I alpha-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum alpha-mannosidase I (ER Man I) and mouse Golgi alpha-mannosidase IA (Golgi Man IA). In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA. 相似文献
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23.
Acyclovir was synthesized in five steps from 7-formamido-5-methylthiofurazano[3,4-d]pyrimidine 2 . Alkylation of 2 with 2-(benzoyloxy)ethoxymethyl chloride, followed by reductive cleavage of the furazan ring gave 9-[[2-(benzoyloxy)ethoxy]methyl]-2-(methylthio)adenine 5 . Hydrolysis of the 6-amino group of 5 , followed by amination of 7 with ammonia gave 9-[(2-hydroxyethoxy)methyl]guanine ( 1 , acyclovir). 相似文献
24.
Schmidt Sherry L. Myers Michele D. Kelley Stephen S. McMillan James D. Padukone Nandan 《Applied biochemistry and biotechnology》1997,(1):469-482
The use of membrane processes for the recovery of fermentation products has been gaining increased acceptance in recent years.
Pervaporation has been studied in the past as a process for simultaneous fermentation and recovery of volatile products such
as ethanol and butanol. However, membrane fouling and low permeate fluxes have imposed limitations on the effectiveness of
the process. In this study, we characterize the performance of a substituted polyacetylene membrane, poly[(l-trimethylsilyl)-l-propyne]
(PTMSP), in the recovery of ethanol from aqueous mixtures and fermentation broths. Pervaporation using PTMSP membranes shows
a distinct advantage over conventional poly(dimethyl siloxane) (PDMS) membranes in ethanol removal. The flux with PTMSP is
about threefold higher and the concentration factor is about twofold higher than the corresponding performance achieved with
PDMS under similar conditions. The performance of PTMSP with fermentation broths shows a reduction in both flux and concentration
factor relative to ethanol-water mixtures. However, the PTMSP membranes indicate initial promise of increased fouling resistance
in operation with cell-containing fermentation broths. 相似文献
25.
Dr. Michael L. Tarlton Dr. Xiaojuan Yu Robert J. Ward Dr. Steven P. Kelley Dr. Jochen Autschbach Dr. Justin R. Walensky 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(58):14396-14400
The coordination of tBuNC and CO with the diarsenido complexes (C5Me5)2An(η2-As2Mes2), An=Th, U, has been investigated. For the first time, a comparison between isostructural complexes of ThIV and UIV has been possible with CO; density functional calculations indicated an appreciable amount of π backbonding that originates from charge transfer from an actinide-arsenic sigma bond. The calculated CO stretching frequencies in the ThIV and UIV diarsenido complexes are consistent with the experimental measurements, both show large shifts to lower frequency. We demonstrate that the π backbonding is crucial to explaining the red shifts of CO frequency upon AnIV complex formation. Interestingly, this interaction essentially correlates to the parallel orientation of π*(C−O) orbitals relative to the An−As bond. 相似文献
26.
27.
Motivated by a simple optimal control problem with state constraints, we consider an inexact implementation of the primal-dual interior point algorithm of Zhang, Tapia, and Dennis. We show how the control problem can be formulated as a linear program in an infinite dimensional space in two different ways and prove convergence results.The research of this author was supported by an Overseas Research Scholarship of the Ministry of Education, Science and Culture of Japan.The research of this author was supported by National Science Foundation grants #DMS-9024622 and #DMS-9321938, North Atlantic Treaty Organization grant #CRG 920067, and an allocation of computing resources from the North Carolina Supercomputing Program.The research of this author was supported by North Atlantic Treaty Organization grant #CRG 920067. 相似文献
28.
We consider the effect of approximation on performance of quasi-Newton methods for infinite dimensional problems. In particular we study methods in which the approximation is refined at each iterate. We show how the local convergence behavior of the quasi-Newton method in the infinite dimensional setting is affected by the refinement strategy. Applications to boundary value problems and integral equations are considered.The research of this author was supported by NSF grant DMS-8601139 and AFOSR grant AFOSR-ISSA-860074. 相似文献
29.
S. L. Campbell I. C. F. Ipsen C. T. Kelley C. D. Meyer 《BIT Numerical Mathematics》1996,36(4):664-675
We present a qualitative model for the convergence behaviour of the Generalised Minimal Residual (GMRES) method for solving nonsingular systems of linear equationsAx =b in finite and infinite dimensional spaces. One application of our methods is the solution of discretised infinite dimensional problems, such as integral equations, where the constants in the asymptotic bounds are independent of the mesh size.Our model provides simple, general bounds that explain the convergence of GMRES as follows: If the eigenvalues ofA consist of a single cluster plus outliers then the convergence factor is bounded by the cluster radius, while the asymptotic error constant reflects the non-normality ofA and the distance of the outliers from the cluster. If the eigenvalues ofA consist of several close clusters, then GMRES treats the clusters as a single big cluster, and the convergence factor is the radius of this big cluster. We exhibit matrices for which these bounds are tight.Our bounds also lead to a simpler proof of existing r-superlinear convergence results in Hilbert space.This research was partially supported by National Science Foundation grants DMS-9122745, DMS-9423705, CCR-9102853, CCR-9400921, DMS-9321938, DMS-9020915, and DMS-9403224. 相似文献
30.
A nonrigid registration algorithm for longitudinal breast MR images and the analysis of breast tumor response 总被引:1,自引:0,他引:1
Xia Li Benoit M. Dawant E. Brian Welch A. Bapsi Chakravarthy Darla Freehardt Ingrid Mayer Mark Kelley Ingrid Meszoely John C. Gore Thomas E. Yankeelov 《Magnetic resonance imaging》2009,27(9):1258-1270
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can estimate parameters relating to blood flow and tissue volume fractions and therefore may be used to characterize the response of breast tumors to treatment. To assess treatment response, values of these DCE-MRI parameters are observed at different time points during the course of treatment. We propose a method whereby DCE-MRI data sets obtained in separate imaging sessions can be co-registered to a common image space, thereby retaining spatial information so that serial DCE-MRI parameter maps can be compared on a voxel-by-voxel basis. In performing inter-session breast registration, one must account for patient repositioning and breast deformation, as well as changes in tumor shape and volume relative to other imaging sessions. One challenge is to optimally register the normal tissues while simultaneously preventing tumor distortion. We accomplish this by extending the adaptive bases algorithm through adding a tumor-volume preserving constraint in the cost function. We also propose a novel method to generate the simulated breast magnetic resonance (MR) images, which can be used to evaluate the proposed registration algorithm quantitatively. The proposed nonrigid registration algorithm is applied to both simulated and real longitudinal 3D high resolution MR images and the obtained transformations are then applied to lower resolution physiological parameter maps obtained via DCE-MRI. The registration results demonstrate the proposed algorithm can successfully register breast MR images acquired at different time points and allow for analysis of the registered parameter maps. 相似文献