The palladium catalysed coupling of aryldiazonium salts with β-γ-unsaturated lactones under basic conditions has been investigated. Both (3H)-furanone and α-angelicalactone were evaluated as substrates in the Heck Matsuda reaction but both failed to afford the desired arylated butenolides. Under basic conditions, β-γ-unsaturated lactones generate highly nucleophilic enolates that preferentially undergo azo coupling reactions with arenediazonium salts to afford aryldiazene butenolides. The electronic and steric effect of the substituents on the aryldiazonium salt in the azo coupling reaction is described. Aryldiazene-lactone derivatives were obtained in good yields from a highly facile and straightforward procedure. An aminoisomaleimide was formed from (3H)-furanone and cyclised to the corresponding pyridazinones in modest yield.

Nitric oxide (•NO) is a substance that acts as a second-messenger and is associated with a number of important physiological functions such as regulation of the vascular tonus, immune modulation and neurotransmission. As a physiological mediator, alteration of its concentration level may cause pathophysiological disfunctions such as hypertension, septic shock and impotence. Possible therapeutic approaches are being developed to control NO levels in vivo. We review herein the main physical and chemical properties of •NO, its biological functions and available chemical interventions to reduce and increment its physiological concentration levels. Recent developments in the field are also highlighted.

An overview of the developments that occurred in the field of organic chemistry in Brazil in the last 25 years is presented. These developments are briefly compared to those observed worldwide, including some modern trends. The main source of information was the annual meeting of the Brazilian Chemical Society (RASBQ) covering the period 1979-2001 and the biennial Brazilian Meeting on Organic Synthesis (BMOS). All the contributions presented at these two meetings were classified according to six main indicatives, to permit a discussion about the past, present and future activities of Organic Chemistry in Brazil.

A primeira síntese total da substância antitumoral de origem marinha metacromina-A (1) foi alcançada através de uma abordagem sintética convergente e aplicável a preparação de análogos para estudos biológicos. A síntese envolveu doze etapas na sua sequência mais longa e dezesseis no total, apresentando como destaques (1) a eficácia na síntese da quinona intermediária 11; (2) a preparação eficiente dos fragmentos chaves 5 e 6; (3) uma reação de acetoxilação do tipo Thiele-Winter altamente regiosseletiva e (4) uma reação de acoplamento do tipo Horner-Wadsworth-Emmons empregando o fragmento 6 como fosfonato não estabilizado capaz de atuar como um agente produtivo no acoplamento. Uma síntese formal e enantiosseletiva da metacromina-A também é descrita a partir da síntese assimétrica do fragmento 5, utilizando as metodologias desenvolvidas por Simpkins (desprotonação assimétrica com bases nitrogenadas quirais) e d’Angelo (alquilações desracemizantes). Este último processo forneceu o fragmento 5 com um excesso enantiomérico de ~85%, determinado por espectroscopia de RMN ¹H.

The first total synthesis of the antineoplastic marine natural product metachromin-A (1) was accomplished through a convergent synthetic approach amenable to the preparation of analogues for biological studies. The synthesis involved twelve steps in its longest sequence and sixteen steps overall. The total synthesis of the racemic metachromin-A features: (1) an efficient synthesis of the quinone intermediate 11; (2) efficient protocols for the preparation of the key fragments 5 and 6; (3) a highly regioselective Thiele-Winter acetoxylation step; and (4) a stereoselective Horner-Wadsworth-Emmons coupling reaction employing fragment 6 as a non-stabilized phosphonate as an effective partner. The metachromin-A synthesis was made formally enantioselective by the asymmetric synthesis of fragment 5 employing the methodologies developed by Simpkins (asymmetric deprotonation with a chiral nitrogenated base) and d’Angelo (enantioselective deracemization). This latter protocol furnished fragment 5 with an enantiomeric excess of ~85%, as determined by ¹H-NMR spectroscopy.