ABSTRACT
A highly diastereoselective microwave-assisted three component synthesis of azabicyclo[2.2.2]octan-5-ones by a silicotungstic acid-catalyzed aza-Diels-Alder cyclization is described. The one-pot process involves the formation of the in situ generated Schiff base and its immediate cyclization with cyclohex-2-enone. The short reaction times, good yields and excellent diastereoselectivity make this annulation a practical and environmentally attractive method for the synthesis of the target compounds. Preliminary assays were carried out to determine the activity of the products in AChE as well as in amyloid ß fibrillogenesis inhibition.
Subject(s)
Acids/chemistry , Alzheimer Disease/metabolism , Aza Compounds/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Catalysis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cyclization , Humans , Microwaves , Molecular Structure , StereoisomerismABSTRACT
The current ultrastructural description of Nosema whitei is in agreement with the genus definition of Paranosema [Sokolova, Y.Y., Dolgikh, V.V., Morzhina, E.V., Nassonova, E.S., Issi, I.V., Terry, R.S., Ironside, J.E., Smith, J.E., Vossbrinck, C.R., 2003. Establishment of the new genus Paranosema based on the ultrastructure and molecular phylogeny of the type species Paranosema grylli Gen. Nov., Comb. Nov (Sokolova, Selezniov, Dolgikh, Issi 1994), from the cricket Gryllus bimaculatus Deg. Journal of Invertebrate Pathology 84, 159-172]. In addition to exhibiting similar spore morphology and sporogony type, N. whitei, like P. grylli and Paranosema locustae, possesses a distinct meront-sporont transitional stage in the life cycle; develops in the host fat body, and produces secretory material arranged in "tubular structures" during sporogony. Ultrastructural analysis supports the similarity of N. whitei to P. grylli and to P. locustae as predicted on the basis SSrDNA sequence data (GenBank Accession Nos. AY305323, AY305325, and AY305324). Comparative studies of these three related species provide a good example of the consistency of morphological and sequence data, and support both the placement of N. whitei inside the genus Paranosema and the validity of the new combination Paranosema whitei (Weiser).
