1.
Arvela, Riina K., et al.
(författare)
Highly regioselective internal heck arylation of hydroxyalkyl vinyl ethers by aryl halides in water
2007
Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 72:17, s. 6390-6396
Tidskriftsartikel (refereegranskat) abstract
Highly regioselective and fast Pd(0)-catalyzed internal α-arylation of ethylene glycol vinyl ether with aryl halides was shown to be possible in water without the need for any halide scavengers or ionic liquid additives. This presents, to our knowledge, the first case of water being utilized in the selective arylation of electron-rich olefins. Resulting α-products were hydrolyzed and isolated as corresponding acetophenones in good to excellent yields when using aryl bromides and with good to moderate yields in the case of aryl iodides. Microwave irradiation was shown to be beneficial in activation of aryl chlorides toward the internal Heck arylation. The scope of the protocol was further increased to include different hydroxyalkyl vinyl ethers, these all giving selectively only branched α-products. Finally, the active role of the hydroxy group in directing the regioselectivity toward internal arylation of electron-rich olefins, even in nonpolar toluene, was revealed.
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4.
Ekegren, Jenny K, et al.
(författare)
Microwave-accelerated synthesis of P1'-extended HIV-1 protease inhibitors encompassing a tertiary alcohol in the transition-state mimicking scaffold
2006
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 49:5, s. 1828-1832
Tidskriftsartikel (refereegranskat) abstract
Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.
5.
Ekegren, Jenny, et al.
(författare)
Variations of the P2 Group in HIV-1 Protease Inhibitors Containing a Tertiary Alcohol in the Transition-State Mimicking Scaffold
2006
Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 4:16, s. 3040-3043
Tidskriftsartikel (refereegranskat) abstract
The development of synthetic protocol leading to HIV-1 protease inhibitors with a tertiary alcohol based transition-state mimicking unit and different P2 side chains was investigated. (2S)-2-benztloxirane-2-carboxylic acid ((S)-5) was used as a key intermediate in the synthesis of the new HIV-1 protease inhibitors. (S)-5 was coupled with different amines using EDC, NMM, and HOBT, resulting in the corresponding amides at low to moderate yields. The observation supports the hypothesis that intramolecular hydrogen bonding to the tertiary alcohol in the transition-state mimic is present in these molecules. Purification by reverse-phase LC-MS resulted in moderate to good yields of most target compounds. The HIV-1 protease inhibition data suggest that the size and polarity of the P2 substituent are crucial to allow proper accommodation in the S2 sub-site.
6.
Enquist, Per-Anders, et al.
(författare)
ESI-MS Detection of Proposed Reaction Intermediates in the Air-Promoted and Ligand-Modulated Oxidative Heck Reaction
2006
Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 71:23, s. 8779-8786
Tidskriftsartikel (refereegranskat) abstract
Electrospray ionization mass spectrometry (ESI-MS) and subsequent MS/MS analyses were used to directly detect palladium-containing cationic reaction intermediates in a ligand controlled palladium(II)-catalyzed oxidative Heck arylation. All potential intermediates were observed as dmphen-ligated palladium(II) species, suggesting that the dmphen bidentate ligand is attached to the metal center during the entire catalytic cycle. The study supports previous mechanistic propositions and provides new information regarding the composition of aryl-containing Pd(II) complexes in an ongoing oxidative Heck reaction. In addition, sodium acetate was found to be a useful base alternative to previously used tertiary amines.
7.
Georgsson, Jennie, et al.
(författare)
Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT2 receptor
2007
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:7, s. 1711-1715
Tidskriftsartikel (refereegranskat) abstract
Four tripeptides corresponding to the C-terminal region of angiotensin II were synthesized. One of these peptides (Ac-His-Pro-Ile) showed moderate binding affinity for the AT2 receptor. Two aromatic histidine-related scaffolds were synthesized and introduced in the tripeptides to give eight new peptidomimetic structures. Three of the new peptide-derived druglike molecules exhibited selective, nanomolar affinity for the AT2 receptor. These ligands may become lead compounds in the future development of novel classes of selective AT2 receptor agonists.
8.
Gising, Johan, et al.
(författare)
A straightforward microwave method for rapid synthesis of N-1, C-6 functionalized 3,5-dichloro-2(1H)-pyrazinones
2009
Ingår i: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 7:13, s. 2809-2815
Tidskriftsartikel (refereegranskat) abstract
A rapid and versatile one-pot, 2 * 10 min microwave protocol for the prepn. of N-1 and C-6 decorated 3,5-dichloro-2(1H)-pyrazinones, e.g., I, from the corresponding primary amines and aldehyde was developed. Comparable reaction sequences using classical conditions require about 1-2 days of heating. The alpha -aminonitrile was first generated in a Strecker reaction and thereafter cyclized under microwave heating. The microwave approach developed offers the possibility of efficiently generating and utilizing functionalized 3-amino-5-chloro-2(1H)-pyrazinone-N-1-carboxylic acids as beta -strand inducing core structures in a medicinal chem. context. To illustrate the usefulness of the method, the synthesis of two novel 2(1H)-pyrazinone-contg. Hepatitis C virus NS3 protease inhibitors, e.g., II, is reported.
9.
Lagerlund, Olof, et al.
(författare)
Aminocarbonylations of Alkenyl Phosphates, Chlorides, Bromides and Triflates with Mo(CO)6 as a Solid CO source
2009
Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 65:36, s. 7646-7652
Tidskriftsartikel (refereegranskat) abstract
Palladium-catalyzed aminocarbonylations of alkenyl chlorides, bromides, and triflates were investigated using Mo(CO)6 as a solid carbon monoxide source. The reactions afforded moderate to good yields producing a wide variety of acrylamides after 20 minutes of microwave irradiation. In addition, the aminocarbonylation reaction was, for the first time, expanded to include alkenyl phosphates as starting materials.
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