Pancreaticogastrostomy versus Pancreaticojejunostomy and the Proposal of a New Postoperative Pancreatic Fistula Risk Score.

Despite the substantial decrease in mortality rates following a pancreaticoduodenectomy to less than 5%, morbidity rates remain significant, reaching even 73%. Postoperative pancreatic fistula is one of the most frequent major complications and is significantly associated with other complications, including patient death. Currently, there is no consensus regarding the ideal type of pancreatic anastomosis, as the question of the choice between a pancreaticogastrostomy and pancreaticojejunostomy is still open. Furthermore, worldwide implementation of an ideal pancreatic fistula risk prediction score is missing. Our study found several significant predictive factors for the postoperative occurrence of fistulas, such as the soft consistency of the pancreas, non-dilated Wirsung duct, important intraoperative blood loss, other perioperative complications, preoperative patient hypoalbuminemia, and patient weight loss. Our study also revealed that for patients who exhibit fistula risk factors, pancreaticogastrostomy demonstrates a significantly lower pancreatic fistula rate than pancreaticojejunostomy. The occurrence of pancreatic fistulas has been significantly associated with the development of other postoperative major complications, and patient death. As the current pancreatic fistula risk scores proposed by various authors have not been consensually validated, we propose a simple, easy-to-use, and sensitive score for the risk prediction of postoperative pancreatic fistula occurrence based on important predictors from statistical analyses that have also been found to be significant by most of the reported studies. The new pancreatic fistula risk score proposed by us could be extremely useful for improved therapeutic management of cephalic pancreaticoduodenectomy patients.

Dynamics of Forest Fragmentation and Connectivity Using Particle and Fractal Analysis.

The ever decreasing area of forests has lead to environmental and economical challenges and has brought with it a renewed interest in developing methodologies that quantify the extent of deforestation and reforestation. In this study we analyzed the deforested areas of the Apuseni Mountains, which has been under economic pressure in recent years and resulted in widespread deforestation as a means of income. Deforested surface dynamics modeling was based on images contained in the Global Forest Database, provided by the Department of Geographical Sciences at Maryland University between 2000 and 2014. The results of the image particle analysis and modelling were based on Total Area (ha), Count of patches and Average Size whereas deforested area distribution was based on the Local Connected Fractal Dimension, Fractal Fragmentation Index and Tug-of-War Lacunarity as indicators of forest fragmentation or heterogeneity. The major findings of the study indicated a reduction of the tree cover area by 3.8%, an increase in fragmentation of 17.7% and an increase in heterogeneity by 29%, while fractal connectivity decreased only by 0.1%. The fractal and particle analysis showed a clustering of forest loss areas with an average increase from 1.1 to 3.0 ha per loss site per year. In conclusion, the fractal and particle analysis provide a relevant methodological framework to further our understanding of the spatial effects of economic pressure on forestry.

Concise total synthesis of glucosepane.

Glucosepane is a structurally complex protein posttranslational modification that is believed to exist in all living organisms. Research in humans suggests that glucosepane plays a critical role in the pathophysiology of both diabetes and human aging, yet comprehensive biological investigations of this metabolite have been hindered by a scarcity of chemically homogeneous material available for study. Here we report the total synthesis of glucosepane, enabled by the development of a one-pot method for preparation of the nonaromatic 4H-imidazole tautomer in the core. Our synthesis is concise (eight steps starting from commercial materials), convergent, high-yielding (12% overall), and enantioselective. We expect that these results will prove useful in the art and practice of heterocyclic chemistry and beneficial for the study of glucosepane and its role in human health and disease.

Synthetic Approaches and Total Syntheses of Vinigrol, a Unique Diterpenoid.

This review summarizes all published total and formal syntheses as well as synthetic approaches towards vinigrol. The content is divided into sections, which are focused on each research groups contributions and how far each approach was advanced towards vinigrol. Graphical summaries of all the published vinigrol structural perspectives, starting materials used for each routes and a discussion of preferred or privileged reactions employed is also presented.

Evolution of an oxidative dearomatization enabled total synthesis of vinigrol.

The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group's importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations.

Synthesis of demissidine by a ring fragmentation 1,3-dipolar cycloaddition approach.

A synthesis of the steroidal alkaloid demissidine from epiandrosterone is reported. A ring fragmentation reaction that efficiently ruptured the D-ring of a diazo ester derivative of epiandrosterone to provide an aldehyde tethered ynoate product was key to this sequence. Incorporation of the indolizidine framework was achieved by an azomethine ylide 1,3-dipolar cycloaddition.

Preparation of tethered aldehyde ynoates and ynones by ring fragmentation of cyclic gamma-oxy-beta-hydroxy-alpha-diazo carbonyls.

Cyclic gamma-oxy-beta-hydroxy-alpha-diazo carbonyls undergo Lewis acid induced ring fragmentation to provide either ynoates or ynones tethered to an aldehyde, ketone, or ester. The fragmentation precursors are convenient to prepare by adding lithiated alpha-diazo carbonyls to alpha-oxy ketones. The fragmentation appears general and provides a variety of functional group-rich products in good to excellent yield.

An efficient synthetic approach to polycyclic 2,5-dihydropyrroles from alpha-silyloxy ketones.

A three-step sequence to prepare polycyclic 2,5-dihydropyrroles from alpha-silyloxy ketones is presented. A Lewis acid-mediated ring fragmentation of cyclic gamma-silyloxy-beta-hydroxy-alpha-diazo esters provided tethered aldehyde ynoate intermediates which, when treated with amino acid silyl esters, underwent intramolecular azomethine ylide 1,3-dipolar cycloadditions. The 2,5-dihydropyrrole products were formed in good to excellent yield as single diastereomers.

Rapid assembly of vinigrol's unique carbocyclic skeleton.

Detailed in this account are our efforts toward the total synthesis of vinigrol. A highly expedient and convergent synthetic approach made possible by the use of a strategic oxidative dearomatization reaction coupled with a series of ensuing substrate controlled transformations is discussed.

Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy-alpha-diazoesters.

Cyclic gamma-silyloxy-beta-hydroxy-alpha-diazoesters undergo efficient rupture of the Cbeta-Cgamma bond when treated with tin tetrachloride to provide tethered aldehyde ynoate products in high yield.

Radical addition approach to asymmetric amine synthesis: design, implementation, and comparison of chiral N-acylhydrazones.

Intermolecular radical addition to C=N bonds with acyclic stereocontrol offers excellent potential as a mild, nonbasic carbon-carbon bond construction approach to chiral amines. Here, complete details of the first radical additions to chiral N-acylhydrazones as an approach to asymmetric amine synthesis are disclosed. Novel N-acylhydrazones were designed as chiral C=N radical acceptors with Lewis acid activation, restriction of conformational mobility, and commercial availability of precursors. Amination of 4-alkyl-2-oxazolidinones with O-(mesitylenesulfonyl)hydroxylamine or O-(p-nitrobenzoyl)hydroxylamine afforded N-aminooxazolidinones which were condensed with aldehydes to afford N-acylhydrazones 3-8. Three synthetic methods were developed, implementing these N-acylhydrazones in Lewis acid-promoted intermolecular radical additions to C=N bonds. First, additions of various secondary and tertiary alkyl iodides to propionaldehyde and benzaldehyde hydrazones (3 and 7) under tin hydride radical chain conditions in the presence of ZnCl2 gave N-acylhydrazine adducts with diastereomeric ratios ranging from 93:7 to 99:1. Radical additions to a series of N-acylhydrazones with different substituents on the oxazolidinone revealed that benzyl and diphenylmethyl were more effective stereocontrol elements than those with the aromatic ring directly attached to the oxazolidinone. Second, a tin-free method, exploiting dual functions of triethylborane for both initiation and chain propagation, enabled improved yields in addition of secondary alkyl iodides. Third, under photolytic conditions with hexamethylditin, primary radical addition could be achieved with ethyl iodide in the presence of diethyl ether as cosolvent; the 1-ethoxyethyl adduct was observed as a minor product. Chloromethyl addition was achieved under both the tin-free and photolytic conditions; in this case, the adduct bears alkyl chloride functionality with potential for further elaboration.