Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids

A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6- substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed

Synthesis of new DPP-4 inhibitors based on a novel tricyclic scaffold

A novel molecular scaffold has been synthesized and its synthesis and incorporation into new analogues of biologically active molecules will be discussed. A comparison of the inhibitory activity of these compounds to the known type-2 diabetes compound (sitagliptin) against dipeptidyl peptidase-4 (DPP-4) will be shown

Replica exchange molecular dynamic simulations for the conformational analyses of synthetic peptides

Different combinations of forcefield and implicit solvation models were compared against their ability to predict the native conformation of a selection of helical peptides, \u3b2-hairpins and intrinsically disordered peptides (IDP), using Replica Exchange Molecular Dynamics (REMD) simulations.[1] A unique combination of force field and implicit solvent model able to accurately predict the experimental structure of all the considered systems was not found. However, we observed that that the force fields of the ff99SB series coupled with GB-Neck2 reasonably discriminated helices from IDPs. Conversely, a decent prediction of \u3b2-hairpin conformations was achieved by combining the ff96 forcefield with either GC-OBC(II) or GB-Neck2 solvent models. Consequently, in order to achieve a true prediction of an unknown peptide, a set of two different simulations are suggested: the first using any of the ff99SB/ildn/ildn-\u3c6 force fields coupled to GB-Neck2, the second using the ff96 force field coupled to GB-Neck2 or GB-OBC(II). Using this knowhow, we applied REMD simulations to predict the conformation of different bioactive or potentially bioactive peptides containing non-natural amino acids. In particular, we will discuss examples concerning helical peptides,[2] cyclopeptides,[3] \u3b2-hairpins,[4] and \u3b3-turns.[5

Tubercular epididymitis and orchitis: US patterns

For several decades tuberculosis has been adequately under control in this country, but there has been recent concern that this disease might be coming back to the forefront, due to the influx of immigrants from developing countries where tuberculosis is still rampant. In the years to come we are expecting an increase in cases of genitourinary lesions of tubercular origin, a disease which had practically disappeared in the Western world. The aim of this pictorial essay is to provide an outline of the typical US images of tubercular epididymitis and orchitis

[Integrated imaging of the breast. Use of a hypermedia program and multimedia archives for teaching purposes]

This paper deals with the results obtained with a computerized senology system developed at the Institute of Radiology of "La Sapienza" University in Rome. The system combines a hypermedia program with a multimedia didactic archive integrated with the radiologic information system. These programs have been developed on Macintosh computers: the hypermedia one on a Macintosh IIfx with 160-Mb hard disk and 8-Mb RAM and a Supercard software, the multimedia archive on Macintosh IIvx, IIvi and Quadra 650 units, connected with an Ethernet network to a server Quadra 950 (RAM: 20 Megabytes; optical disk: 1 Giga) and using the 4th Dimension as software. The basics of breast anatomy, radiologic semiology and breast diseases are illustrated with the hypermedia program: such a system has many advantages to teach the basics requiring just a process of learning by heart. The multimedia archive allows to classify a large number of difficult and uncommon clinical cases, according to the ACR code. Thus, it is useful also to teachers to study particular subjects, including anatomical variants and uncommon conditions. In conclusion, we believe these systems to be valuable tools in the formation and update of the physicians devoted to the study of breast diseases

An integrated approach to senology education: combination of a hypermedia program with a multimedia archive

The aim of this work was to demonstrate the computerized system on senology, which combines a hypermedia application to a multimedia didactical archive, integrated with a radiological information system. These applications have been developed on Macintosh computers using the softwares Supercard and 4th Dimension. The hypermedia application deals with basic principles of anatomy as well as the radiologic semeiology and pathology through different imaging techniques in order to illustrate basic principles. Thus, students can modify their learning pathways and the timing as they wish. Limitations are related to time consumption in preparing the programs and technical difficulties in expanding them. Multimedia archive allows to classify a large number of difficult and uncommon clinical cases, creating an easily updatable teaching file in digital format which considerably improves access to stored image data, also reducing loss of films and film degradation. From initial experiences we conclude that these systems are valid devices in information and up to date for physicians dedicated to the study of breast pathology