Functionalization at C-5 and at the C-6 methyl group of 4-methoxy-6-methyl-2-pyrone

A new entry to C-5 substituted 4-hydroxy-6-methyl-2-pyrones has been achieved. The best conditions to prepare the monobromo and the dibromo derivatives at C-3 and the C-6 methyl group of the title pyrone have been defined. The synthetic applicability of the phosphonium salts at CH₃-C-6 of both 4-methoxy-6-methyl-2-pyrone, 5 , and dehydroacetic acid, 2 , has also been evaluated.     

Synthesis of imidazo[4,5-c]pyridines with a trifluoromethyl group at C-4 and/or C-6

Thermal condensation of histamine with trifluoroacetaldehyde gives 4-(trifluoromethyl)spinacamine and subsequent dehydrogenation with selenium dioxide leads to 4-(trifluoromethyl)-1H-imidazo[4,5-c]pyridine (42%). Fluorination with sulfur tetrafluoride of L-spinacine, obtained from the condensation of L-histidine with formaldehyde, affords 6-(trifluoromethyl)spinacamine, which can be converted to 6-(trifluoromethyl)-1H-imidazo[4,5-c]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4-(trifluoro-methyl)-L-spinacine gives 4,6-bis(trifluoromethyl)-1H-imidazo[4,5-c]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sulfur tetrafluoride.     

Chemistry of pyrones related to dehydroacetic acid. Functionalization at C-5 and at the methyl group at C-6. An attempted synthesis of a thromboxane B2 analogue

New derivatives of dehydroacetic acid and triacetic acid lactone functionalized at both C-5 and at the methyl group at C-6 have been synthesized as intermediates for the preparation of thromboxane B₂ analogues. 6-Mercaptomethyl-4-methoxy-2-pyrone and some derived thioethers have been also prepared. New thioether derivatives of O-alkyloximes of dehydroacetic acid have been synthesized and tested for herbicidal activity.     

Proline derived spirobarbiturates as highly effective beta-turn mimetics incorporating polar and functionalizable constraint elements

A practical and efficient synthesis of spirobarbiturates of type III is reported when NH acidity of the imide function of the hydrophilic linker element allowed the introduction of different substituents. Structural characterization, which was based on both X-ray crystallography and spectroscopic investigations, indicated type II beta-turn formation. Introduction of the molecular scaffold into solid phase peptide synthesis gave rise to spirocyclic neuropeptide analogs.     

Cyclization of some labdane alcohols with a hydroxy group at C-13 by a superacid

On the superacid cyclization of the labdane alcohols manool, isomanool, and sclareol the tetracyclic hydrocarbon (1S,2R,11S,12R,15R)-2,7,7,11,15-pentamethyltetracyclo[10.2.1.0^2,11.0^3,8]pentadec-3(8)-ene with a new carbon skeleton is formed.Institute of Chemistry, Moldavian SSR Academy of Sciences, Kishinev. Novosibirsk Institute of Organic Chemistry, Siberian Branch, USSR Academy of Sciences. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 198–203, March–April, 1988.     

Chiral Deuteration at C-6 of 1,6-Anhydrohexose Derivatives

Photobromination and the succeeding deuteration with tri-n-butyltindeuteride were performed on eight l,6-anhydro-2,3,4-tri-O-benzoylhexopyranoses to give C-6 chirally deuterated hexopyranoses. The stereochemistry of these two reactions are discussed in terms of steric effects of substituents at C-2, C-3 and C-4 of 1,6-anhydrohexopyranoses.     

Chemoselective functionalization of α-carbolines at the C-2, C-3, C-4, and C-6 positions using Suzuki-Miyaura reactions

The synthesis of 2-, 3-, 4-, and 6-substituted pyrido[2,3-b]indoles (α-carbolines) by palladium-catalyzed cross-coupling reactions from the corresponding halopyrido[2,3-b]indoles is described. A sequential and a one-pot chemoselective double Suzuki-Miyaura coupling route is presented for the synthesis of symmetrically and unsymmetrically disubstituted pyrido[2,3-b]indoles.     

Methoxymethyl (MOM) group nitrogen protection of pyrimidines bearing C-6 acyclic side-chains

Novel N-methoxymethylated (MOM) pyrimidine (4-13) and pyrimidine-2,4-diones (15-17) nucleoside mimetics in which an isobutyl side-chain is attached at the C-6 position of the pyrimidine moiety were synthesized. Synthetic methods via O-persilylated or N-anionic uracil derivatives have been evaluated for the synthesis of N-1- and/or N-3-MOM pyrimidine derivatives with C-6 acyclic side-chains. A synthetic approach using an activated N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed the predominant conformation of the compound to be one where the hydroxymethyl group in the C-6 side-chain is close to the N-1-MOM moiety, while the OMTr is in proximity to the CH(3)-5 group. Contrary to this no NOE enhancements between the N-1-MOM group and hydroxymethyl or fluoromethyl protons in 13 were observed, which suggested a nonrestricted rotation along the C-6 side-chain. Fluorinated N,N-1,3-diMOM pyrimidine 13 emerged as a model compound for development of tracer molecules for non-invasive imaging of gene expression using positron emission tomography (PET).