6812-26-6Relevant articles and documents
Synthesis of 6-Hydroxysphingosine and α-Hydroxy Ceramide Using a Cross-Metathesis Strategy
Wisse, Patrick,De Geus, Mark A. R.,Cross, Gen,Van Den Nieuwendijk, Adrianus M. C. H.,Van Rooden, Eva J.,Van Den Berg, Richard J. B. H. N.,Aerts, Johannes M. F. G.,Van Der Marel, Gijsbert A.,Codée, Jeroen D. C.,Overkleeft, Herman S.
, p. 7258 - 7265 (2015/07/27)
(Chemical Equation Presented) In this paper, a new synthetic route toward 6-hydroxysphingosine and α-hydroxy ceramide is described. The synthesis employs a cross-metathesis to unite a sphingosine head allylic alcohol with a long-chain fatty acid alkene that also bears an allylic alcohol group. To allow for a productive CM coupling, the sphingosine head allylic alcohol was protected with a cyclic carbonate moiety and a reactive CM catalyst system, consisting of Grubbs II catalyst and CuI, was employed.
βUnsaturated acyl cyanides as new bis-electrophiles for enantioselective organocatalyzed formal [3+3]spiroannulation
Goudedranche, Sebastien,Bugaut, Xavier,Constantieux, Thierry,Bonne, Damien,Rodriguez, Jean
supporting information, p. 410 - 415 (2014/04/03)
α,β-Unsaturated acyl cyanides are key bis-electrophile substrates for successful domino enantioselective organocatalyzed Michael-intramolecular acylation domino sequences. This new reactivity has been applied to the synthesis of enantioenriched azaspiro[4
Mechanism-Based inactivation of human cytochrome p450 3A4 by two piperazine-Containing compounds
Bolles, Amanda K.,Fujiwara, Rina,Briggs, Erran D.,Nomeir, Amin A.,Furge, Laura Lowe
, p. 1471 - 1475 (2014/12/11)
Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of more than half of pharmaceutic drugs, and inactivation of CYP3A4 can lead to adverse drug-drug interactions. The substituted imidazole compounds 5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl) methyl]-1-piperazinyl]pyrimidine (SCH 66712) and 1-[(2-ethyl-4-methyl-1H-imidazol-5-yl)methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine (EMTPP) have been previously identified as mechanism-based inactivators (MBI) of CYP2D6. The present study shows that both SCH 66712 and EMTPP are also MBIs of CYP3A4. Inhibition of CYP3A4 by SCH 66712 and EMTPP was determined to be con-centration, time, and NADPH dependent. In addition, inactivation of CYP3A4 by SCH 66712 was shown to be unaffected by the presence of electrophile scavengers. SCH 66712 displays type I binding to CYP3A4 with a spectral binding constant (Ks) of 42.9 ± 2.9 μM. The partition ratios for SCH 66712 and EMTPP were 11 and 94, respectively. Whole protein mass spectrum analysis revealed 1:1 binding stoichiometry of SCH 66712 and EMTPP to CYP3A4 and a mass increase consistent with adduction by the inactivators without addition of oxygen. Heme adduction was not apparent. Multiple monooxygenation products with each inactivator were observed; no other products were apparent. These are the first MBIs to be shown to be potent inactivators of both CYP2D6 and CYP3A4.
A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations
Tasic, Gordana,Randjelovic, Jelena,Vusurovic, Nikola,Maslak, Veselin,Husinec, Suren,Savic, Vladimir
, p. 2243 - 2246 (2013/05/21)
Intramolecular Pd-catalysed cyclisation reactions for the preparation of bicyclic compounds have been studied as a model system towards the synthesis of corialstonine and corialstonidine. Significant differences in reactivity have been observed for the cyclic allyl alcohols possessing O-protected and free OH functionalities. Cyclisation via the intramolecular Heck reaction, for both derivatives, proved to be highly regioselective and while the O-protected compound favoured the exo mode of cyclisation, the unprotected alcohol preferred the endo cyclisation pathway. Brief computational studies were carried out in order to obtain further insight into these processes.
Synthesis of eight 1-deoxynojirimycin isomers from a single chiral cyanohydrin
Van Den Nieuwendijk, Adrianus M.C.H.,Van Den Berg, Richard J.B H.N.,Ruben, Mark,Witte, Martin D.,Brussee, Johannes,Boot, Rolf G.,Van Der Marel, Gijsbert A.,Aerts, Johannes M.F.G.,Overkleeft, Herman S.
scheme or table, p. 3437 - 3446 (2012/08/27)
Eight configurational 1-deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1-deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.
Enantioselective total synthesis of the unnatural and the natural stereoisomers of vittatalactone
Schmidt, Yvonne,Lehr, Konrad,Breuninger, Ulrich,Brand, Gabriel,Reiss, Tomislav,Breit, Bernhard
scheme or table, p. 4424 - 4433 (2010/10/01)
(Figure presented) The striped cucumber beetle, Acalymma vittatum, is a cause of major damage to cucurbit crops in North America. To develop an environmentally benign plant protection strategy, recent research has focused on identifying sex pheromones of
Chiral linear polymers bonded alternatively with salen and 1,4-dialkoxybenzene: Synthesis and application for Ti-catalyzed asymmetric TMSCN addition to aldehydes
Sakthivel, Sekarpandi,Punniyamurthy, Tharmalingam
experimental part, p. 2834 - 2840 (2011/03/19)
The synthesis of chiral linear polymers 1a-b having salen and 1,4-dioctyloxybenzene as alternate segments has been accomplished. The GPC analysis showed the molecular weights corresponding to ca. 15 (Mw = 10,999, Mn = 9165 and PDI = 1.20) repeating units for 1a and ca. 8 (Mw = 8547, Mn = 7883 and PDI = 1.08) repeating units for 1b. Polymers 1a-b have been studied with Ti(OiPr)4 as a recyclable catalyst for the asymmetric addition of TMSCN to aldehydes while the selectivity of the polymer catalyst is identical to that of the monomer. The reactions are efficient affording the cyanohydrins with up to 88% ee. The selectivity of the polymer based catalyst 9a is found to be the same to that of the monomer 10a. The reaction provides the advantages of simplified product isolation and easy recovery and recyclability of polymer catalyst 9a without any loss of activity or selectivity.
A unified strategy for the stereospecific construction of propionates and acetate-propionates relying on a directed allylic substitution
Reiss, Tomislav,Breit, Bernhard
supporting information; experimental part, p. 6345 - 6348 (2010/01/16)
A strategy for the stereospecific construction of propionates and acetate-propionates using a directed allylic substitution was reported. The enantiomerically pure allylic o-DPPB esters having an additional oxygen functionality in the homoallylic position served as the building blocks for iterative propionate insertion. It was observed that asymmetric sharpless epoxidation of allylic alcohol followed by an epoxide ring opening with a hydride nucleophile produced the acetate-propionate structures. The process allowed the stereoselective construction of 1,5-skipped oligomethyl chains of isoprenoid or polyketide origin. Crotonaldehyde was used and treated with HCN in the presence of the oxynitrilase from bitter almonds to furnish the (R)-cyanohydrin with high levels of enantioselectivity. The nitrile function was transformed into the ethyl ester using a Pinner reaction protocol.
PmHNL catalyzed synthesis of (R)-cyanohydrins derived from aliphatic aldehydes
Nanda, Samik,Kato, Yasuo,Asano, Yasuhisa
, p. 735 - 741 (2007/10/03)
Hydroxynitrile lyase from the Japanese apricot (Prunus mume) catalyzes the formation of several aliphatic cyanohydrins in an asymmetric fashion. By employing a biphasic reaction system, aliphatic aldehydes with various structural features can be converted to the corresponding (R)-cyanohydrins with good overall yield and enantiomeric excess.
Synthesis of E-vinylogous (R)-amino acid derivatives via metal-catalyzed allylic substitutions on enzyme-derived substrates
Deardorff, Donald R.,Taniguchi, Cullen M.,Nelson, Anna C.,Pace, Andrew P.,Kim, Alexander J.,Pace, Aaron K.,Jones, Regan A.,Tafti, Sanaz A.,Nguyen, Charles,O'Connor, Caitlin,Tang, Judy,Chen, Judy
, p. 1655 - 1661 (2007/10/03)
Oxynitrilase-derived allylic (R)-cyanohydrin carbonates 3 and allylic (R)-α-hydroxy ester carbonates 6 were examined as substrates for a palladium(0)-catalyzed allylic azidation reaction. The enantioselectivities and cis/trans diastereoselectivities of the concomitant 1,3-chirality transposition step were studied. The cyano carbonates 3a-c were found to be unimpressive substrates producing γ-azido-α,β-unsaturated nitriles 4a-c with cis/trans ratios that approached unity and gave enantiomeric excesses that ranged from 57% to 85%. In contrast, ester carbonates 6a and b were excellent substrates for the reaction exclusively affording trans substitution products 7a and b in identical enantiomeric excesses of 95% ee.
