Effects of methyl groups on the geometry and conformational equilibrium of 1,3-dioxanes

The geometries and energies of polymethyl-1,3-dioxanes were studied by molecular mechanics calculations. Buttressing effects of the Me groups are discussed. The chair/twist conformational equilibrium of 1,3-dioxanes having two syn-axial Me groups in the chair were calculated, and a twist form (the 1,4-twist) is found to be more stable than the chair only for 9 and 14, chair and 2,5-twist form are of comparable energies for 10 and 13, and the chair is considerably favored in 11 and 12. The chair/1,4-twist energy difference of 1 was calculated to be only 16.4 kJ mol^?1. Ring inversion of 1 goes through a transition state with C-C-C-O coplanar with a calculated activation enthalpy of 28.3 kJ mol^?1.     

Konformationen von 1,3-dioxanen nach der kraftfeldmethode. nichtbindende wechselwirkungen von sauerstoff

The treatment of oxygen lone pairs in force field calculations is discussed. The geometries of 1,3-dioxanes can be calculated well without explicit account of lone pairs. For the calculation of conformational energies in 5-alkyl-1,3-dioxanes electrostatic interactions between point charges taken from quantum mechanical calculations must be included. Addition of van der Waals interactions of lone pairs as weak potentials further improves the calculated conformational energies.     

Configuration-Odor Relationships in 5β-Ambrox

The four possible A/B cis-fused diastereoisomers of Ambrox® have been synthesized and their configurations and conformations established by X-ray and NMR analysis. Only 5β-ambrox (= 1,2,3a,4,5,5β,6,7,8,9,9a,9bα-dodecahydro-3aβ,6,6,9aβ-tetramethylnaphtho[2,1-b]furan; 5 ) has an odor quality comparable to Ambrox®. The 1,3-synperiplanar/diaxial conformation of the substituents at C(8) ( = C(3a)) and C(10) (= C(9a)) has thus been confirmed to be a compulsory structure element for the particular odor.     

Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules

Bid is a key member of the Bcl-2 family proteins involved in the control of the apoptotic cascade in cells, leading to cell death. Uncontrolled cell death is associated with several human pathologies, such as neurodegenerative diseases and ischemic injuries. Therefore, Bid represents a potential yet unexplored and challenging target for strategies aimed at the development of therapeutic agents. Here we show that a multidisciplinary NMR-based approach that we named SAR by ILOEs (structure activity relationships by interligand nuclear Overhauser effect) allowed us to rationally design a series of 4-phenylsulfanyl-phenylamine derivatives that are capable of occupying a deep hydrophobic crevice on the surface of Bid. These compounds represent the first antiapoptotic small molecules targeting a Bcl-2 protein as shown by their ability to inhibit tBid-induced SMAC release, caspase-3 activation, and cell death.     

Electroexcitation of nucleon resonances

In these lectures the status of electromagnetic excitation of nucleon resonances is reviewed and some of the open problems of the structure and spectroscopy of light-quark baryons are discussed. The basic formalism for describing electromagnetic processes is introduced but not derived.Lecture given at the 8th Summer School on Intermediate-Energy Physics: Hadron Dynamics at Low and Intermediate Energies, Prague, July 10–14, 1995.     

Beiträge zur Chemie des Sulfamids, 1. Mitt.: Zur Konstitution des Disilber-sulfamids

According to spectroscopic (IR, broadline proton NMR) and chemical (alkylation) investigations of disilver sulphamide the following molecular structure is assumed: $$\begin{gathered} O \hfill \\ || \hfill \\ H_2 N\_\_S\_\_NAg| \hfill \\ OAg \hfill \\ \end{gathered}$$ From the IR and NMR data deduction concerning the nature of the chemical bonds in this compound is possible. The instability of the still unknown mono-and trisilver sulphamide is discussed with regard to the structure of disilver sulphamide.     

Conformational analysis3̄CXXIV: The conformation of ring A in the 4,4-dimethyl-3-androstanone system. The crystal structure of 4,4-dimethylandrostan-3-on-17β-yl benzoate

Molecular mechanics calculations indicate that the deformed chair and twisted-boat conformations are similar in energy for a 4,4-dimethyl-3-keto steroid. Earlier dipole moment work on such compounds is discussed. The crystal structure of 4,4-dimethylandrostan-3-on-17β-yl benzoate has been determined. The crystals are orthorhombic, P2₁2₁2₁, a = 17.096 (2), b = 22.136 (e), c = 6.217 (1) A. The structure was solved by direct methods and refined by least squares to R ? 0.039, R_XXX = 0.038, based on 2168 observed reflections. Ring A is shown to exist in a chair form, deformed as indicated by the calculations.     

Neue Phellandren-Derivate aus dem Wurzelöl von Angelica archangelicaL

New Phellandrene Derivatives from the Root Oil of Angelica archangelica L . 2-Nitro-1,5-p-menthadiene ( 5 ), trans- and cis-6-nitro-1(7), 2-p-menthadiene ( 6 and 7 ), trans-1(7), 5-p-menthadien-2-yl acetate ( 9 ) and a formal phellandrene derivative, 7-isopropyl-5-methyl-5-bicyclo [2.2.2]octen-2-one ( 16 ), have been identified in the root oil of Angelica archangelica L . Starting from (?)-(R)-α-phellandrene ( 1 ) (R)- 5 , (4R, 6S)- 6 /(4R, 6R)- 7 , (2S, 4R)- 9 and (1R, 4R, 7R)- 16 as well as (2S, 4R)- 11 , (2R, 4R)- 12 and (2R, 4R)- 10 have been prepared.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.