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R Hernandez

Publications and source records attributed to R Hernandez.

At least 19 recordsLinked to original sources
PubMed2006

Effects of polyethylene glycol and hydroxyethyl starch in University of Wisconsin preservation solution on human red blood cell aggregation and viscosity.

University of Wisconsin (UW) preservation solution is considered an effective flush and cold storage liquid. However, recent studies have provided evidence of the hyperaggregating effect on human red blood cells (RBC) of hydroxyethyl starch (HES), one of the components of the UW solution. In contrast, preservation solutions containing polyethylene glycol (PEG) have been found to be effective for organ preservation. The aim of this study was to compare the effects of HES (50 g/L); PEG 20 kDa (50 and 30 g/L), and PEG35 kDa (1.05 g/L) added to UW on the rheologic parameters of human RBC at 4 degrees C. Sedimentation rate was measured by the Westergren procedure and blood viscosity evaluated at high shear rates using a cone/plate viscometer. Alterations in RBC morphology and aggregation were evaluated by light microscopy. RBC sedimentation and viscosity were not affected by the inversion of Na+ and K+ concentrations in UW, but were increased by HES. PEGs appeared to reduce RBC deformability with concomitant inhibition of RBC aggregation. These results were consistent with reduced viscosity for PEG-containing solutions. In conclusion, the use of PEG did not change the physiologic function of human RBCs and thus may be an alternative to HES in UW liquids.

Adenosine↗
PubMed2006

Clinical effectiveness and cost-effectiveness of laparoscopic surgery for colorectal cancer: systematic reviews and economic evaluation.

OBJECTIVE: The aim of this study was to determine the clinical effectiveness and cost-effectiveness of laparoscopic, laparoscopically assisted (hereafter together described as laparoscopic surgery) and hand-assisted laparoscopic surgery (HALS) in comparison with open surgery for the treatment of colorectal cancer. DATA SOURCES: Electronic databases were searched from 2000 to May 2005. A review of economic evaluations was undertaken by the National Institute for Health and Clinical Excellence in 2001. This review was updated from 2000 until July 2005. REVIEW METHODS: Data from selected studies were extracted and assessed. Dichotomous outcome data from individual trials were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Summaries of the results from individual patient data (IPD) meta-analyses were also presented. An economic evaluation was also carried out using a Markov model incorporating the data from the systematic review. The results were first presented as a balance sheet for comparison of the surgical techniques. It was then used to estimate cost-effectiveness measured in terms of incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) for a time horizon up to 25 years. RESULTS: Forty-six reports on 20 studies [19 randomised controlled trials (RCTs) and one IPD meta-analysis] were included in the review of clinical effectiveness. The RCTs were of generally moderate quality with the number of participants varying between 16 and 1082, with 10 having less than 100 participants. The total numbers of trial participants who underwent laparoscopic or open surgery were 2429 and 2139, respectively. A systematic review of four papers suggested that laparoscopic surgery is more costly than open surgery. However, the data they provided on effectiveness was poorer than the evidence from the review of effectiveness. The estimates from the systematic review of clinical effectiveness were incorporated into a Markov model used to estimate cost-effectiveness for a time horizon of up to 25 years. In terms of incremental cost per life-year, laparoscopic surgery was found to be more costly and no more effective than open surgery. With respect to incremental cost per QALY, few data were available to differentiate between laparoscopic and open surgery. The results of the base-case analysis indicate that there is an approximately 40% chance that laparoscopic surgery is the more cost-effective intervention at a threshold willingness to pay for a QALY of pound 30,000. A second analysis assuming equal mortality and disease-free survival found that there was an approximately 50% likelihood at a similar threshold value. Broadly similar results were found in the sensitivity analyses. A threshold analysis was performed to investigate the magnitude of QALY gain associated with quicker recovery following laparoscopic surgery required to provide an incremental cost per QALY of pound 30,000. The implied number of additional QALYs required would be 0.009-0.010 compared with open surgery. CONCLUSIONS: Laparoscopic resection is associated with a quicker recovery (shorter time to return to usual activities and length of hospitalisation) and no evidence of a difference in mortality or disease-free survival up to 3 years following surgery. However, operation times are longer and a significant number of procedures initiated laparoscopically may need to be converted to open surgery. The rate of conversion may be dependent on experience in terms of both patient selection and performing the technique. Laparoscopic resection appears more costly to the health service than open resection, with an estimated extra total cost of between pound 250 and pound 300 per patient. In terms of relative cost-effectiveness, laparoscopic resection is associated with a modest additional cost, short-term benefits associated with more rapid recovery and similar long-term outcomes in terms of survival and cure rates up to 3 years. Assuming equivalence of long-term outcomes, a judgement is required as to whether the benefits associated with earlier recovery are worth this extra cost. The long-term follow-up of the RCT cohorts would be very useful further research and ideally these data should be incorporated into a wider IPD meta-analysis. Data on the long-term complications of surgery such as incisional hernias and differences in outcomes such as persisting pain would also be valuable. Once available, further data on both costs and utilities should be included in an updated model. At this point, further consideration should then be given as to whether additional data should be collected within ongoing trials. Few data were available to assess the relative merits of HALS. Ideally, there should be more data from methodologically sound RCTs. Further research is needed on whether the balance of advantages and disadvantages of laparoscopic surgery varies within subgroups based on the different stages and locations of disease. Research relating to the effect of experience on performance is also required.

Colorectal Neoplasms↗
PubMed2005

Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats.

AIMS/HYPOTHESIS: Although thiazolidinediones are now widely used to treat type 2 diabetes, their mechanism of action remains largely unknown. They are agonists for the transcription factor PPARgamma, and in addition to their insulin-sensitising effects, they can promote adipogenesis and control gene expression in adipose tissues. We have explored the effect of rosiglitazone on insulin-mediated induction of pivotal genes involved in lipid metabolism and thermogenesis in brown fat. The genes studied were: (1) lipoprotein lipase (lpl), which is involved in lipid uptake; (2) hormone-sensitive lipase (hsl), which mobilises fatty acids from stored triglycerides; (3) fatty acid synthase (fas), which regulates de novo lipogenesis; and (4) the uncoupling proteins (ucp) 1 and 3, which control thermogenesis. METHODS: We used fetal rat primary brown adipocytes cultured with insulin, rosiglitazone or both combined. Then, we studied gene expression by northern and western blotting, as well as 'run-on' and gel-shift assays to identify binding of potential transcription factors to the fas promoter. RESULTS: Exposure to rosiglitazone for 24 h induced ucp-1, lpl and hsl gene expression and when rosiglitazone was combined with insulin a synergistic effect on lpl and ucp-3 mRNA expression was produced. These effects were consistent with increased LPL and HSL activities as well as respiration rates, mainly in response to exogenous palmitate. In contrast, treatment with rosiglitazone did not alter FAS mRNA basal levels but prevented the induction elicited by insulin in a time- and dose-dependent manner. Correspondingly diminished FAS protein levels and activity, as well as cellular lipid content, were observed, indicating an antilipogenic action of rosiglitazone in brown adipocytes. Furthermore, rosiglitazone impaired insulin increase in the FAS transcription rate by antagonising insulin-induced binding of upstream stimulatory factors to the E-box consensus sequence in the FAS promoter and insulin-induced binding of activating protein-1. CONCLUSIONS/INTERPRETATION: Rosiglitazone prevents insulin-induced up-regulation of the main lipogenic enzyme but increases the expression of those enzymes involved in lipid uptake and mobilisation, favouring fatty acid utilisation through uncoupled respiration.

Adipocytes↗
PubMed2004

Rosiglitazone ameliorates insulin resistance in brown adipocytes of Wistar rats by impairing TNF-alpha induction of p38 and p42/p44 mitogen-activated protein kinases.

AIMS/HYPOTHESIS: TNF-alpha caused insulin resistance on glucose uptake and on insulin signalling in fetal brown adipocytes. Since treatment with TNF-alpha activates stress kinases, including c-jun NH2 terminal kinase (JNK), and p42/p44 and p38 mitogen-activated protein kinases (MAPK), we explored the contribution of these pathways to insulin resistance by TNF-alpha. Rosiglitazone is used to treat Type 2 diabetes as it improves insulin sensitivity in vivo. However, its ability to ameliorate TNF-alpha-induced insulin resistance in brown adipocytes remains to be explored. METHODS: We used fetal rat primary brown adipocytes cultured with TNF-alpha, with or without stress kinase inhibitors or rosiglitazone, and further stimulated with insulin. Then, we measured glucose uptake and GLUT4 translocation. To determine the insulin signalling cascade, we submitted cells to lysis, immunoprecipitation and immunoblotting. RESULTS: Exposure to TNF-alpha for 24 h impairs insulin stimulation of the phosphatidylinositol (PI) 3-kinase activity associated with IRS-2 and Akt activity. Pretreatment with PD98059 or PD169316, which inhibit p42/p44MAPK and p38MAPK respectively, restored insulin signalling and insulin-induced glucose uptake in the presence of TNF-alpha. However, in the presence of SP600125, an inhibitor of JNK, TNF-alpha still produced insulin resistance. Rosiglitazone ameliorated insulin resistance by TNF-alpha in brown adipocytes, restoring completely insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane in parallel to the insulin signalling cascade IRS-2/PI 3-kinase/Akt. CONCLUSIONS/INTERPRETATION: Rosiglitazone treatment impaired TNF-alpha activation of p38 and p42/p44MAPK, restoring insulin signalling and leading to normalisation of glucose uptake.

Adipocytes↗
PubMed2004

Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction (MI). DATA SOURCES: Major electronic databases. REVIEW METHODS: Two reviewers independently extracted data and assessed study quality. A decision tree model was used to model the diagnosis decision and a Markov model was developed for the management of patients with suspected coronary artery disease. Costs for the treatments and interventions within strategies were derived from the literature and expressed in 2001-02 pounds sterling. Quality-adjusted life-year (QALY) weights for the different Markov model states were also obtained from the literature. RESULTS: Twenty-one diagnostic and 46 prognostic studies were included, plus two studies comparing SPECT with electrocardiography (ECG)-gated SPECT and one study comparing SPECT with attenuation-corrected SPECT. The diagnostic values of SPECT were generally higher than those of stress ECG, indicating that SPECT provided a better diagnostic performance. SPECT also provided higher positive and lower negative likelihood ratios than stress ECG but heterogeneity was evident among studies. The subgroup of studies including patients with previous MI tended to report a better diagnostic performance for SPECT than stress ECG, but there were too few studies to assess this reliably. The extent and size of the perfusion defect, and whether reversible or fixed, were important factors in predicting future cardiac events such as cardiac death or non-fatal MI. SPECT may be able to identify lower risk patients for whom coronary angiography (CA) might be avoided. Normal SPECT scans were associated with a benign prognosis and the option of medical rather than invasive management. Four studies of patients post-MI reported SPECT to be valuable in stratifying patients into at-risk groups for further cardiac events. The two studies comparing SPECT with ECG-gated SPECT, one diagnostic and the other prognostic, found in favour of gated SPECT. The study comparing SPECT with attenuation-corrected SPECT reported the latter to be more accurate. The systematic review of economic evaluations indicated that strategies involving SPECT were likely either to be dominant or to produce more QALYs at an acceptable cost. There was less agreement about which of the strategies involving SPECT was optimal. The model suggested that, for low prevalence, the incremental cost per unit of output (true positives diagnosed, accurate diagnosis, QALY) for the move from stress ECG-SPECT-CA and from stress ECG-CA to SPECT-CA might be considered worthwhile. Even after allowing for different values for sensitivity or specificity, the least costly and least effective strategy was stress ECG-SPECT-CA. The sensitivity analysis suggested that the cost-effectiveness of SPECT-CA improved if it was assumed that SPECT results allowed for the adoption of a management strategy without recourse to CA. As the time horizon reduced, the incremental cost per QALY increased (as the cost of initial diagnosis and treatment were not offset by survival and quality of life gains). CONCLUSIONS: There was a considerable variability in terms of measurement of outcomes, management, setting and patient characteristics, however the direction of evidence tended to favour SPECT in terms of test sensitivity, although these conclusions are based on a relatively small number of diagnostic studies. SPECT, in a variety of settings and patient populations, provided valuable independent and incremental prognostic information to that provided by stress ECG and/or CA that helped to risk-stratify patients and influence the way in which their condition was managed. However, all of the prognostic studies were observational studies and may be biased by unknown confounding factors. Although the ECG-gated and attenuation-corrected SPECT findings seem promising, it is difficult to draw conclusions from so few studies. Further research is needed on the effectiveness and cost-effectiveness, diagnostically and prognostically, of (a) gated and attenuation-corrected SPECT compared with standard SPECT, (b) standard SPECT compared with stress echocardiography and (c) the uncertainty surrounding the results presented in the cost-effectiveness analysis.

Angina Pectoris↗
PubMed2003

Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes.

AIMS/HYPOTHESIS: Rosiglitazone is used to treat Type 2 diabetes because it improves insulin sensitivity. However, the specific molecular mechanism by which this compound acts has not yet been explained. METHODS: We used fetal rat primary brown adipocytes cultured for 24 h with or without 10 micro mol/l rosiglitazone and further stimulated for 5 min with 10 nmol/l insulin. Next we measured glucose uptake and GLUT4 translocation and submitted the cells to lysis, immunoprecipitation and immunoblotting in order to measure the insulin signalling cascade. RESULTS: Rosiglitazone noticeably activated basal glucose uptake in a manner dependent on p38-mitogen-activated protein kinase. Rosiglitazone also produced a 40% increase in insulin-stimulated glucose uptake as a result of increased GLUT4 translocation to the plasma membrane. This happened without changes in the expression of GLUT4 at the mRNA or protein level. This effect correlated with the potentiation by rosiglitazone of insulin-stimulated Tyr phosphorylation of insulin receptor substrate-1 and to a greater extent of insulin receptor substrate-2. It also correlated with the subsequent activation of phosphatidylinositol 3-kinase and Akt, without changes in protein kinase Czeta activity. Rosiglitazone treatment increased insulin receptor expression and insulin-stimulated Tyr phosphorylation of insulin receptor beta-chain, but decreased insulin-stimulated Ser phosphorylation. It also potentiated insulin-induced Tyr phosphorylation of insulin receptor beta-chain and protein tyrosine phosphatase 1B in co-immunoprecipitates and impaired insulin activation of protein tyrosine phosphatase 1B activity. CONCLUSIONS/INTERPRETATION: At the insulin receptor level, rosiglitazone-induced improvements of insulin sensitivity result from two convergent mechanisms: increased insulin receptor expression and insulin receptor activation.

Adipocytes↗
PubMed2002

Allele frequency and gene expression of a putative carboxylesterase-encoding gene in a pyrethroid resistant strain of the tick Boophilus microplus.

We utilized RNA Northern blot analysis and ribonuclease protection assays (RPA) to study the mRNA expression level of a putative carboxylesterase-encoding gene from several strains of Boophilus microplus (Canestrini). Both the Northern analysis and RPAs indicated that an esterase transcript was more abundant in the pyrethroid resistant strain, Coatzacoalcos (Cz), compared to a susceptible control strain and a resistant strain whose pyrethroid resistance is mediated through a target site insensitivity mechanism. A PCR-based assay was designed to identify the presence of a previously reported point mutation in this B. microplus esterase gene. The reported G-->A substitution at nucleotide 1120 creates an EcoR I site in the mutant allele which can be detected by EcoR I digestion of the amplification products. The PCR assays showed that the frequency of the mutant allele was highest in the Cz-resistant strain, which has been shown to have an esterase-mediated resistance mechanism. The PCR assay can be performed either on individual tick larvae or hemolymph from adults.

Alleles↗
PubMed2002

Identification of highly transformable wheat genotypes for mass production of fertile transgenic plants.

The efficiency of wheat biolistic transformation systems strongly depends on the bombardment parameters, the condition of the donor plant, and the plant genotype chosen for the transformation process. This paper analyzes the transformation efficiency of the 129 wheat sister lines generically called 'Bobwhite', originally obtained from the cross 'Aurora'//'Kalyan'/'Bluebird 3'/'Woodpecker'. A number of factors influencing the transformation were examined, such as the ability to produce embryogenic callus, regeneration in selection medium, and overall transformation performance. Of the 129 genotypes evaluated, eight demonstrated transformation efficiencies above 60% (60 independent transgenic events per 100 immature embryos bombarded). Among the eight genotypes identified, we studied agronomic characteristics such as earliness to identify the most adaptable line(s) for different lab conditions. 'Bobwhite' SH 98 26 was identified as a super-transformable wheat line.

Biolistics↗
PubMed2002

Isolation and identification of an esterase from a Mexican strain of Boophilus microplus (Acari: Ixodidae).

A strain of Mexican Boophilus microplus (Cz) collected near Coatzacoalcos, Veracruz, Mexico, exhibits a moderate, but significant, level of permethrin resistance. Unlike other highly permethrin resistant strains, the Cz strain does not have a mutation within the sodium channel gene that results in target-site insensitivity. However, the Cz strain possesses a substantial increase in general and permethrin esterase activity relative to highly permethrin resistant and control strains suggesting the involvement of a metabolic esterase(s) in the expression of permethrin resistance. We report the isolation of a 62.8 kDa protein from Cz strain larvae that we think is the esterase previously reported as Cz EST9. In addition, internal amino acid sequence data obtained from the 62.8 kDa protein suggest that it is the gene product of a previously reported B. microplus carboxylesterase cDNA. We propose that the 62.8 kDa protein (Cz EST9) has permethrin hydrolytic activity and as a result plays an important role in Cz strain resistance to permethrin.

Amino Acid Sequence↗
PubMed2001

A minimalist model protein with multiple folding funnels.

Kinetic and structural studies of wild-type proteins such as prions and amyloidogenic proteins provide suggestive evidence that proteins may adopt multiple long-lived states in addition to the native state. All of these states differ structurally because they lie far apart in configuration space, but their stability is not necessarily caused by cooperative (nucleation) effects. In this study, a minimalist model protein is designed to exhibit multiple long-lived states to explore the dynamics of the corresponding wild-type proteins. The minimalist protein is modeled as a 27-monomer sequence confined to a cubic lattice with three different monomer types. An order parameter-the winding index-is introduced to characterize the extent of folding. The winding index has several advantages over other commonly used order parameters like the number of native contacts. It can distinguish between enantiomers, its calculation requires less computational time than the number of native contacts, and reduced-dimensional landscapes can be developed when the native state structure is not known a priori. The results for the designed model protein prove by existence that the rugged energy landscape picture of protein folding can be generalized to include protein "misfolding" into long-lived states.

Amino Acid Sequence↗
PubMed2001

Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene expression in brown adipocytes.

Insulin acutely stimulated glucose uptake in rat primary brown adipocytes in a PI3-kinase-dependent but p70S6-kinase-independent manner. Since Akt represents an intermediate step between these kinases, this study investigated the contribution of Akt to insulin-induced glucose uptake by the use of a chemical compound, ML-9, as well as by transfection with a dominant-negative form of Akt (DeltaAkt). Pretreatment with ML-9 for 10 min completely inhibited insulin stimulation of (1) Akt kinase activity, (2) Akt phosphorylation on the regulatory residue Ser473 but not on Thr308, and (3) mobility shift in Akt1 and Akt2. However, ML-9 did not affect insulin-stimulated PI3-kinase nor PKCzeta activities. In consequence, ML-9 precluded insulin stimulation of glucose uptake and GLUT4 translocation to plasma membrane (determined by Western blot), without any effect on the basal glucose uptake. Moreover, DeltaAkt impaired insulin stimulation of glucose uptake and GFP-tagged GLUT4 translocation to plasma membrane in transiently transfected immortalised brown adipocytes and HeLa cells, respectively. Furthermore, ML-9 treatment for 6 h down-regulated insulin-induced GLUT4 mRNA accumulation, without affecting GLUT1 expression, in a similar fashion as LY294002. Indeed, co-transfection of brown adipocytes with DeltaAkt precluded the transactivation of GLUT4-CAT promoter by insulin in a similar fashion as a dominant-negative form of PI3-kinase. Our results indicate that activation of Akt may be an essential requirement for insulin regulation of glucose uptake and GLUT4 gene expression in brown adipocytes.

Adipocytes↗
PubMed2001

Exposure to low pH is not required for penetration of mosquito cells by Sindbis virus.

It is widely held that the penetration of cells by alphaviruses is dependent on exposure to the acid environment of an endosome. The alphavirus Sindbis virus replicates in both vertebrate and invertebrate cell cultures. We have found that exposure to an acid environment may not be required for infection of cells of the insect host. In this work, we investigated the effects of two agents (NH(4)Cl and chloroquine), which raise the pH of intracellular compartments (lysosomotropic weak bases) on the infection and replication of Sindbis virus in cells of the insect host Aedes albopictus. The results show that both of these agents increase the pH of endosomes, as indicated by protection against diphtheria toxin intoxication. NH(4)Cl blocked the production of infectious virus and blocked virus RNA synthesis when added prior to infection. Chloroquine, in contrast to its effect on vertebrate cells, had no inhibitory effect on infectious virus production in mosquito cells even when added prior to infection. Treatment with NH(4)Cl did not prevent the penetration of virus RNA into the cell cytoplasm or translation of the RNA to produce a precursor to virus nonstructural proteins. These data suggest that while these two drugs raise the pH of endosomes, they do not block insect cell penetration. These data support previous results published by our laboratory suggesting that exposure to an acid environment within the cell may not be an obligatory step in the process of infection of cells by alphaviruses.

Aedes↗
PubMed2001

Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state.

Tumor necrosis factor (TNF)-alpha causes insulin resistance on glucose uptake in fetal brown adipocytes. We explored the hypothesis that some effects of TNF-alpha could be mediated by the generation of ceramide, given that TNF-alpha treatment induced the production of ceramide in these primary cells. A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4. These effects were not produced in the presence of a biologically inactive ceramide analog, C2-dihydroceramide. Analysis of the phosphatidylinositol (PI) 3-kinase signaling pathway indicated that C2-ceramide precluded insulin stimulation of Akt kinase activity, but not of PI-3 kinase or protein kinase C-zeta activity. C2-ceramide completely abolished insulin-stimulated Akt/protein kinase B phosphorylation on regulatory residues Thr 308 and Ser 473, as did TNF-alpha, and inhibited insulin-induced mobility shift in Akt1 and Akt2 separated in PAGE. Moreover, C2-ceramide seemed to activate a protein phosphatase (PP) involved in dephosphorylating Akt because 1) PP2A activity was increased in C2-ceramide- and TNF-alpha-treated cells, 2) treatment with okadaic acid concomitantly with C2-ceramide completely restored Akt phosphorylation by insulin, and 3) transient transfection of a constitutively active form of Akt did not restore Akt activity. Our results indicate that ceramide produced by TNF-alpha induces insulin resistance in brown adipocytes by maintaining Akt in an inactive dephosphorylated state.

Adipocytes↗
PubMed2001

Acute stent thrombosis visualized by intravascular ultrasound.

Subacute stent thrombosis is currently a rare but feared complication in patients undergoing coronary intervention. Intravascular ultrasound is a useful technique to guide stent implantation. However, its value in patients suffering from acute stent thrombosis has not been described. Herein, we present the intravascular ultrasound findings of a patient experiencing ongoing stent thrombosis and impending vessel closure.

Adult↗
PubMed2000

Tandem radical decarboxylation-oxidation of amino acids: A mild and efficient method for the generation of N-acyliminium ions and their nucleophilic trapping

A convenient methodology for the synthesis of 2-substituted pyrrolidines from alpha-amino acids is described. A number of cyclic and acyclic alpha-amino acid derivatives have been prepared in order to test the scope and diastereoselectivity of this method. These substrates were treated with iodosylbenzene or (diacetoxyiodo)benzene (DIB) and iodine in order to generate the corresponding carboxyl radical, which evolves by loss of carbon dioxide to produce a carbon radical which in turn undergoes oxidation to an N-acyliminium ion. This postulated intermediate could be trapped inter- or intramolecularly by oxygen, nitrogen and carbon nucleophiles. In the case of carbon nucleophiles, a Lewis acid is required for the concomitant carbon-carbon bond formation. High yields and modest diastereoselectivities were obtained. The present methodology was applied to the synthesis of omega-amino aldehydes or hemiaminals 8-14, 2-aminopyrrolidine derivative 15, aminolactone derivative 16, and azasugar analogues 17 and 18. When carbon nucleophiles were used, alkaloid precursors such as 2-allyl- or 2-alkylpyrrolidines 19-23 and 25 were obtained.

Journal Article↗