1.Cyclohexenylboration of Aldehydes and Ketones with the Borabicyclo[3.3.2]decanes (BBDs).
González E1, Muñoz-Hernández L1, Alicea E1, Singaram B2, Kabalka GW3, Soderquist JA1. Org Lett. 2015 Sep 4;17(17):4368-71. doi: 10.1021/acs.orglett.5b02194. Epub 2015 Aug 18.
Asymmetric hydroboration of 1,3-cyclohexadiene with 4R produces the allylborane 5RR as essentially a single diastereomer (i.e., no observable 5RS), and its addition to representative aldehydes provides 9RS (52-75%) with excellent selectivity (94-99% ee). By contrast, a similar sequence with the 10-Ph-BBD reagent, 14R, results in a ca. 45:55 mixture of 15RR and 15RS. However, their addition to methyl ketones provides the corresponding 3°-homoallylic alcohols (18RS) with excellent selectivity (80-99% ee) but in low yields (15-52%) because 15RS is unreactive toward either allylboration or isomerization to 15RR. Thus, with 2 equiv of 15, the yield of 18 (R = Ph) is increased from 52% to 85%. Boranes 5SS and 15SS provide enantiomeric alcohols.
2.Theoretical Electronic Circular Dichroism Study of 1,3-Diene Derivatives for the Elucidation of ECD Spectra of 1,3-Cyclohexadiene and Its Derivatives.
Nakayama N1, Goto H2. Chirality. 2015 Aug;27(8):476-8. doi: 10.1002/chir.22465. Epub 2015 May 18.
The origin of P- or M-chirality of methyl substituted 1,3-cyclohexadienes are elucidated by time-dependent density functional theory (TD-DFT) calculation of 1,3-cyclohexadiene derivatives and acyclic 1,3-dienes. The sign-inversion of the rotatory strength of the lowest excited state between 1,3-cyclohexadiene and (5R)-axial-methyl-1,3-cyclohexadiene is caused by the conformation around the (C=)C-C(-Me) dihedral angle. The correlation between the sign of the rotatory strength and conformation has been found not only in methyl substituted derivatives but also fluoro substituted compounds.
3.Discovery and biological evaluation of novel 1,4-benzoquinone and related resorcinol derivatives that inhibit 5-lipoxygenase.
Filosa R1, Peduto A, Aparoy P, Schaible AM, Luderer S, Krauth V, Petronzi C, Massa A, de Rosa M, Reddanna P, Werz O. Eur J Med Chem. 2013 Sep;67:269-79. doi: 10.1016/j.ejmech.2013.06.039. Epub 2013 Jun 27.
5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases. Here, we present the discovery and biological evaluation of novel series of 1,4-benzoquinones and respective resorcinol derivatives that efficiently inhibit human 5-LO, with little effects on other human lipoxygenases. SAR analysis revealed that the potency of the compounds strongly depends on structural features of the lipophilic residues, where bulky naphthyl or dibenzofuran moieties favor 5-LO inhibition. Among the 1,4-benzoquinones, compound Ig 5-[(2-naphthyl)methyl]-2-hydroxy-2,5-cyclohexadiene-1,4-dione potently blocked 5-LO activity in cell-free assays with IC50 = 0.78 μM, and suppressed 5-LO product synthesis in polymorphonuclear leukocytes with IC50 = 2.3 μM. Molecular docking studies suggest a concrete binding site for Ig in 5-LO where select π-π interactions along with hydrogen bond interactions accomplish binding to the active site of the enzyme.
4.Reactive and unreactive pathways in a photochemical ring opening reaction from 2D femtosecond stimulated Raman.
Valley DT1, Hoffman DP, Mathies RA. Phys Chem Chem Phys. 2015 Apr 14;17(14):9231-40. doi: 10.1039/c4cp05323k. Epub 2015 Mar 11.
Two-dimensional femtosecond stimulated Raman spectroscopy (2D-FSRS) is used to probe the structural evolution of a modified cyclohexadiene as it undergoes a photoinduced ring opening reaction. Analysis of the excited state stimulated Raman vibrational data reveals oscillations of the center frequencies and amplitudes of 21 high frequency modes. These oscillations in vibrational properties are due to anharmonic couplings between the high frequency finger print modes and the impulsively driven low frequency molecular distortions in the excited state. The largest anharmonic couplings, with intrinsic oscillation magnitudes of up to 40 cm(-1), are observed between the 467 cm(-1) C-C bend and the 1333 cm(-1) C-C stretch with the 191 cm(-1) methyl wag, all of which are centered on the reactive cyclohexadiene moiety. Conversely, motions located on the periphery - the 993 cm(-1) phenyl bend, the 1389 cm(-1) methyl bend and 1580 cm(-1) phenyl C-C stretch - are coupled with the 104 cm(-1) asymmetric bend.