Hydroboration-Oxidation of (±)-(1α,3α,3aß,6aß)-1,2,3,3a,4,6a-Hexahydro-1,3-pentalenedimethanol and Its O-Protected Derivatives: Synthesis of New Compounds Useful for Obtaining (iso)Carbacyclin Analogues and X-ray Analysis of the Products.

Hydroboration-oxidation of 2α,4α-dimethanol-1ß,5ß-bicyclo[3.3.0]oct-6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60% yield, together with the monobenzoate diol 4a (37%), resulting from the reduction of the closer benzoate by the intermediate alkylborane. The corresponding alkene and dialdehyde gave only the triols 8 and 9 in ~1:1 ratio. By increasing the reaction time and the temperature, the isomerization of alkylboranes favours the un-symmetrical triol 9. The PDC oxidation of the alcohols gave cleanly the corresponding ketones 5 and 6 and the deprotection of the benzoate groups gave the symmetrical ketone 14, and the cyclic hemiketal 15, all in high yields. The ethylene ketals of the symmetrical ketones 11 and 13 were also obtained. The compounds 5, 6, 11, 13, 14 could be used for synthesis of new (iso)carbacyclin analogues. The structure of the compounds was established by NMR spectroscopy and confirmed by X-ray crystallography.

New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of base to the ring and a L configuration of the nucleoside analogues. The compounds were tested for anticancer activity.

The Veneto Region's Barrett's Oesophagus Registry: aims, methods, preliminary results.

BACKGROUND: The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. AIMS: The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. METHODS: An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. RESULTS: In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female=3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients (p<0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e., progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. CONCLUSION: A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.