15547-39-4Relevant academic research and scientific papers
Chiral DNA gyrase inhibitors. 3. Probing the chiral preference of the active site of DNA gyrase. Synthesis of 10-fluoro-6-methyl-6,7-dihydro-9- piperazinyl-2H-benzo[a]quinolizin-20-one-3-carboxylic acid analogues
Fecik, Robert A.,Devasthale, Pratik,Pillai, Segaran,Keschavarz-Shokri, Ali,Shen, Linus,Mitscher, Lester A.
, p. 1229 - 1236 (2007/10/03)
In pursuit of an apparent literature anomaly, S- and R-6-methyl-6,7- dihydro-2H-benzo[a]-quinolizin-2-one-3-carboxylic acids (12 and 22) were synthesized by an unambiguous route from optically active norephedrines, and their antibacterial potencies were measured. Against Gram-negative microorganisms and DNA gyrase a preference for S-absolute configuration was found whereas R-absolute stereochemistry was more active against Gram-positives. These results are in partial conflict with an earlier report. In an attempt to enhance potency, racemic 10-fluoro-9-piperazinyl (35) and related analogues were synthesized by a novel route. The latter analogues were surprisingly unimproved in potency. The implications of these findings are briefly discussed.
Diastereo- and enantioselective synthesis of vicinal amino alcohols by oxa Michael addition of N-formylnorephedrine to nitro alkenes
Enders, Dieter,Haertwig, Andreas,Raabe, Gerhard,Runsink, Jan
, p. 1771 - 1792 (2007/10/03)
The first intermolecular asymmetric oxa Michael additions with removable chirality information within the hydroxide source are reported. As enantiopure oxygen nucleophile functioning as chiral hydroxide equivalent N-formylnorephedrine (7) was used and conjugate additions to aliphatic (E)-nitro alkenes 2a-j were carned out in good yields (35-87%) and excellent diastereomeric excesses (de = 94-≥98%). After reduction of the nitro group and protection of the amino function (11a-h, 73-87%, both steps), the cleavage of the auxiliary occurred without epimerisation (69-99%) using Na/NH3. The Boc-protected 2-amino alcohols 12a-h could be obtained in good overall yields (30-58 %, four steps) and excellent diastereomeric and enantiomeric excesses (de, ee = 94-≥98%). Transition states explaining the overall stereochemical outcome are presented based on the absolute configuration determined by X-ray structure analysis on 8b.
Scope and Limitations of the TiCl4-Mediated Additions of Isocyanides to Aldehydes and Ketones with Formation of α-Hydroxycarboxylic Acid Amides
Seebach, Dieter,Adam, Geo,Gees, Thomas,Schiess, Martin,Weigand, Wolfgang
, p. 507 - 518 (2007/10/02)
The adducts obtained from TiCl4 and achiral (8-12) or chiral, nonracemic (13-22) isocyanides are combined with aldehydes (aromatic or aliphatic) and ketones (acetone, cyclohexanone, acetophenone) to give, after aqueous workup, α-hydroxyamides (27-55) .The transformation is compatible with a variety of functional groups (aromatic and heterocyclic rings, amino, ether, ester, and amido groups, halides, and phosphonate substituents).The yields range from 14 to over 95percent (with the lower values in the case of more highly functionalised isocyanides).No diastereoselectivity is observed with chiral isocyanides.If the R groups of the isocyanide (R-NC) form a rather stable cation (t-alkyl or benzylic), cyanohydrins may result from the reaction, rather than the N-substituted α-hydroxyamides (see Scheme 2).
