Synthesis and GABA(A) receptor activity of 2,19-sulfamoyl analogues of allopregnanolone.

The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the beta-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3alpha-substituted analogues such as the 3alpha-fluoro derivative. GABA(A) receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [(3)H]flunitrazepam and [(3)H]muscimol. The 3alpha-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [(3)H]flunitrazepam. For the binding of [(3)H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC(50). The 3alpha-fluoro derivative was inactive in both assays.

Endoscopic endonasal approach to pituitary adenomas / Abordagem endonasal endoscópica em adenomas de hipófise

Microscopic transsphenoidal surgery is beyond any doubt a widely accepted and highly effective therapy for pituitary adenomas. Currently several centers have converted to an endoscopic transsphenoidal approach; suggesting that this technique provides more complete tumor resection, better visualization and reduce complications. However, there have been few series to document the results of this procedure. This report presents the technical details and compares it to the results of the microscopic method based on the experience of the group and a literature review. The endoscopic transnasal/ transsphenoidal technique is a safe and effective method for removal of pituitary adenomas. The results found in the literature suggest that the endoscope provides more complete tumor removal, and reduces complications. We believe that the advantages of the endoscopic technique will allow this procedure to become the future gold standard surgical therapy for pituitary adenomas.

A cirurgia trans-esfenoidal por meio de microscópio é sem dúvida um procedimento amplamente aceito e altamente efetivo no tratamento cirúrgico dos adenomas pituitários. Hoje em dia muitos centros tem modificado a via trans-esfenoidal endo- nasal, utilizando-se do endoscópio. Esta técnica tem demonstrado um maior índice de ressecção tumoral, uma visão melhor do leito cirúrgico, principalmente nos cantos e na margem junto ao seio cavernoso, e traz um menor índice de complicações. Os resultados da literatura têm demonstrado ser um procedimento seguro, e acreditamos que, devido às suas vantagens, se tornará uma conduta cirúrgica padrão ouro para os adenomas pituitários.

Synthesis of 6,19-sulfamidate bridged pregnanes.

Conformationally restrained substituted pregnane-20-one derivatives were obtained by an intramolecular nitrene addition onto a C-5/C-6 double bond involving a tethered C-19 sulfamoyl moiety. The resulting aziridine underwent regioselective nucleophilic ring opening at C-5 at room temperature with cyanide, fluoride, and acetate. In the isolated case of acetate, a reversal of regioselectivity was observed at higher temperatures, a result attributed to a rearrangement process involving aziridine ring opening at the C-5 position and subsequent migration of the acetyl moiety to C-6.

Intramolecular PhI=O mediated copper-catalyzed aziridination of unsaturated sulfamates: a new direct access to polysubstituted amines from simple homoallylic alcohols.

[reaction: see text] Olefinic sulfamates derived from primary and secondary alcohols undergo intramolecular copper-catalyzed aziridination in the presence of iodosylbenzene to afford novel bicyclic fused aziridines. The latter were opened by various nucleophiles to give the corresponding substituted cyclic sulfamates, which in turn reacted, after nitrogen activation, with a second nucleophile at the carbon atom bearing the oxygen atom. Concomitant removal of the sulfonyloxy moiety thus gave access to polysubstituted amines.