No abstract

2,3-Dihydrobenzofurans can be diastereoselectively prepared by condensation of aromatic aldehydes with 2,3-dihydrobenzoxasilepines under the catalysis of Ag(I) complexes, and in the presence of a source of fluoride ion. The application of this strategy by using chiral catalysts leads to a new enantioselective total synthesis of natural cis-pterocarpans and their trans isomers. Through this method, the first enantioselective total synthesis of the antifungal agent (-)-pterocarpin was achieved. In addition, a new entry into the heteroaromatic system of 2,5-dihydrobenzoxepine is also presented.

The condensation of 2,3-dihydrobenzoxasilepins with aromatic aldehydes in the presence of boron trifluoride to form 2,3-dihydrobenzofurans shows a level of diastereoselection which is a function of the electronic nature of the aldehyde and the polarity of the solvent. The study of the mechanism of the reaction demonstrated that it proceeds through a ring-opened allylfluorosilane, which is stable enough to be isolated and characterized.

BackgroundDecitabine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) de novo or secondary, according to the classification of the WHO, who are not candidates for conventional induction chemotherapy. There is a general recommendation about the maximum refrigerated (2–8°C) storage time for decitabine of 3 hours, but studies designed to explore stability beyond this period have not been conducted to date.PurposeTo evaluate the physical and chemical stability of decitabine stored in polyethylene syringes over a 24 hour period using proton nuclear magnetic resonance (1H-NMR) spectroscopy.Material and methodsCommercial solutions of decitabine (Dacogen) 5 mg/mL (50 mg in 10 mL of sterile water for injection) were packaged in polyethylene syringes. The syringe was stored in a refrigerator at 4°C±2°C for 24 hours in a digitalised temperature controlled chamber. The following physical parameters were monitored: turbidity and colour. Chemical stability was assessed by means of 1H-NMR spectroscopy. The 1H-NMR spectrum of a reference molecule was acquired. Spectroscopic signals were interpreted and assigned to the chemical structure of decitabine, and then consecutive spectra were acquired every hour during the 24 hour period. Signals obtained in these experiments were compared with those of the reference compound. All spectra were acquired using a Bruker Avance DRX 300 MHz spectrometer equipped with a 5 mm single axis z gradient quattro nucleus probe (Bruker Biospin GmbH, Rheinstetten, Germany).ResultsPhysical parameters monitored remained unchanged over the 24 hour period. During 7 hours, the chemical structure of the molecule was maintained unaltered, as demonstrated by 1H-NMR spectra identical to those of the reference compound. However, several signals corresponding to byproducts appeared in the sample stored at 4°C after 7 hours, proving that decitabine had suffered a degradation pathway.ConclusionDecitabine preserved its physical and chemical properties when stored packaged in polyethylene syringes for up to 7 hours at 4°C±2°C. This study comes into conflict with the information data sheet provided with decitabine, which recommends a maximum time of refrigerated (2–8°C) storage of 3 hours.References and/or acknowledgementsUniversity of Almería.No conflict of interest

Other natural products U 0800Silver-Catalyzed Asymmetric Synthesis of 2,3-Dihydrobenzofurans: A New Chiral Synthesis of Pterocarpans. -Condensation of aromatic aldehydes containing an ortho-ester moiety (II) with benzooxasilepine derivatives (I) proceeds readily in the presence of silver catalyst to afford the 2,3-disubstituted 2,3-dihydrobenzofurans in absolute trans-selectivity. This method is developed to an asymmetric version and applied to the synthesis of enantiopure trans-pterocarpin (VI), which isomerizes to cis-pterocarpin (VII) in the presence of CSA. Interestingly, condensation of oxasilepin (Ib) with o-unsubstituted benzaldehydes (VIII) does not afford cyclized products but homoallylic alcohols (IX)/(X) without any diastereoselectivity. Attempts to cyclize these alcohols to 2,3-cis-benzofurans under Mitsunobu conditions are not successful. -(JIMENEZ-GONZALEZ, L.; GARCIA-MUNOZ, S.; ALVAREZ-CORRAL, M.; MUNOZ-DORADO, M.; RODRIGUEZ-GARCIA*, I.; Chem. Eur. J. 12 (2006) 34, 8762-8769; Dep. Quim. Org., Univ. Almeria, E-04120 Almeria, Spain; Eng.) -Mischke 11-205