A mild, stereoselective, and quick approach to accessing alkynyl and alkenyl C-glycosides via BF(3)·Et(2)O promoted coupling of organotrifluoroborates and glycosyl fluorides is reported. The application of this method was further demonstrated by the concise and efficient total synthesis of (+)-varitriol in only seven steps.

Our structure−activity relationship studies with N6-(2-(4-(1H-indol-5-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine derivatives led to development of a lead compound (−)-21a which exhibited very high affnity (Ki, D2 = 16.4 nM, D3 = 1.15 nM) and full agonist activity (EC50 (GTPγS); D2 = 3.23 and D3 = 1.41 nM) at both D2 and D3 receptors. A partial agonist molecule (−)-34 (EC50 (GTPγS); D2 = 21.6 (Emax = 27%) and D3 = 10.9 nM) was also identified. In a Parkinson’s disease (PD) animal model, (−)-21a was highly effcacious in reversing hypolocomotion in reserpinized rats with a long duration of action, indicating its potential as an anti-PD drug. Compound (−)-34 was also able to elevate locomotor activity in the above PD animal model significantly, implying its potential application in PD therapy. Furthermore, (−)-21a was shown to be neuroprotective in protecting neuronal PC12 from toxicity of 6-OHDA. This report, therefore, underpins the notion that a multifunctional drug like (−)-21a might have the potential not only to ameliorate motor dysfunction in PD patients but also to modify disease progression by protecting DA neurons from progressive degeneration.

An organocatalytic intramolecular Stetter-type hydroacylation reaction between an aldehyde and an activated alkyne has been developed. This study induces salicylaldehyde-derived alkyne derivatives to assemble into a series of chromone derivatives using a catalytic amount of thiazoliumbased carbene catalyst.Keywords: chromones; hydroacylation; N-heterocyclic carbenes; organocatalysis; Stetter reaction Over the past few decades, the development of N-heterocyclic carbenes (NHC) has made important headways due to their extensive applicability in several reactions.[1] Besides the role as excellent ligands in the metal-catalyzed reactions, [2a-c] their ability to efficiently catalyze a number of organic reactions, most notably benzoin condensation, [2d-j] Stetter reaction, [3] transesterification [3h] and homo-enolate addition, [4] has contributed significantly to organic transformations. In 1973, Stetter established the first conjugate addition of aldehydes to a,b-unsaturated ester adopting the cyanide ion as the initial catalyst, [5a] and subsequently using a thiazolium-based carbene catalyst.[5b,c] The recent intermolecular variants of the Stetter reaction set in motion an expanding usage of NHCs as organocatalysts for carbon-carbon bond formation.[6] By exploiting an intramolecular Stetter reaction, Trost [7a] constructed a tricyclic system in order to synthesize hirsutic acid. Pioneering studies carried out by Ciganek, [7b] Enders [7c] and Rovis [7d,e] resulted in the development of intramolecular cyclizations as an access to various chromones. In addition, Glorius [8a,b] and She [8c] embarked on intramolecular acyl anion additions to unactivated olefin to construct the chromone scaffolds.Chromones are useful heterocyclic motifs found commonly in pharmaceutical compounds and they often exhibit fascinating therapeutic effects.[9] Our interest in drug discovery [10] motivated us to devise new methodologies for the chromone synthesis. Recently, we reported an NHC-catalyzed intramolecular crosscoupling between the aldehyde and the nitrile function to afford 3-aminochromones in high yields [11] [Scheme 1, Eq. (1)]. A comparison of this chemistry to that of the Stetter reaction [Scheme 1, Eq. (2)] prompted us to investigate the possibility of a newly designed carbon-carbon bond forming reaction Scheme 1. NHC-catalyzed C À C bond formation strategy.

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The present study reports the design and synthesis of nine C 2 -symmetric 5,15-[bis(arayl)]-10α,20β-[bis(1,2:3,4-di-O-isopropylidene-α-D-galactopyranose-6-yl)]porphyrins (3-11) bearing electron donating or electron withdrawing substituents and a D 2 -symmetric 5α,10β,15α,20β-tetrakis(1,2:3,4di-O-isopropylidene-α-D-galactopyranose-6-yl)porphyrin ( 12). In the system we design, the C 6 of pyranose sugar is elegantly fused into the porphyrin core as meso carbon, which renders a new type of photodynanic inducers. The biological effects of these derivatives were assessed in HeLa and HCT116 human cancer cells. In particular, the tetra-glycofused structure 12 exhibited the highest cellular uptake and photocytotoxicity. Unlike the reported sugar-porphyrin conjugates, which normally localize in mitochondria or endoplasmic reticulum, the unique glycofused pophyrins in this study were dominantly localized in lysosomes. The measurement of the dual flurorescence of annexin V-FITC/PI by flow cytometry revealed that the cell death was caused by apoptosis. Further PARP cleavage study suggested that apoptosis induced by the treatment of compound 12 was via caspase-dependent apoptotic pathway in cancer cells.