The first and second cinchona rearrangement. Two fundamental transformations of alkaloid chemistry

Stereochemistry, products, and driving forces of the "first and second Cinchona rearrangement" have been investigated and a unified theory is presented. The first cage expansion affords [3.2.2]azabicyclic alpha-amino ether and is formulated via a configurationally stable bridgehead iminium ion and quasiequatorial nucleophilic attack. The second cage expansion affords beta-functionalized [3.2.2]azabicycles. In this case a nonclassical nitrogen-bridged cation is postulated to account for retention of configuration and potential reversibility of the cage expansion. The second rearrangement is favored for the so-called cinch bases (6'-R = H) in trifluoroethanol. Stereoelectronic factors, electron demand at C9, ground state conformation, and solvent type are crucial in all cases. A two-step protocol for preparing 9-epi-configured Cinchona alkaloids from 9-nat precursors is described.     

Dual role for phenylalanine 178 during catalysis by aristolochene synthase

A mutant of aristolochene synthase, in which Phe 178 was replaced by Val, produced significant amounts of alpha-and beta-farnesene as well as alpha and beta-selinene and selina-4,11-diene, suggesting that Phe 178 is involved in the stabilisation of transition states preceding germacrene A and following eudesmane cation.     

Three-body recombination at large scattering lengths in an ultracold atomic gas

We study three-body recombination in an optically trapped ultracold gas of cesium atoms with precise magnetic control of the s-wave scattering length a. At large positive values of a, we measure the dependence of the rate coefficient on a and confirm the theoretically predicted scaling proportional to a(4). Evidence of recombination heating indicates the formation of very weakly bound molecules in the last bound energy level.     

High-pressure selectivity studies--a simple route to a homochiral wistarin precursor

The cycloaddition of spirobutenolide 3 to the homochiral cyclopentadiene 1 at 6.5 kbar leads exclusively to cycloadduct 5. Subsequent Diels-Alder or Michael additions again favour the cyclohexenone double bond; this perfect chemo- regio- and face selectivity was employed for a short and efficient approach to the wistarin framework.     

Evidence for environmentally coupled hydrogen tunneling during dihydrofolate reductase catalysis

Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga maritima has been studied by stopped flow spectroscopy. The reduction of dihydrofolate by NADPH showed a biphasic temperature dependence of the deuterium kinetic isotope effect. At temperatures above 25 degrees C the KIE was temperature independent, while the reaction rates were strongly temperature dependent. Below 25 degrees C the KIE becomes dependent on temperature, and the ratio of the preexponential factors is inverse, suggesting a greater role for active dynamics that modulate the tunneling distance.     

Direct versus conjugate addition to a terphenyl substituted alkynyl difluoro silane

Alkynyl difluoro silanes can react with nucleophiles either directly at the silane unit by displacing the fluorine atoms (direct addition) or, in contrast, the nucleophile can attack the β -carbon of the adjacent alkynyl group (conjugate addition). By using this type of conjugate addition a number of fascinating unsaturated silicon and germanium compounds have been prepared in the past using alkyl substituted phenyl groups as substituents. Therefore we wanted to investigate which regioselectivity isobserved in the case of such an alkynyl difluoro silane shielded by a terphenyl substituent (Mes₂C₆H₃-, Mes =2,4,6-trimethylphenyl). Surprisingly, the reaction with phenyl lithium leads exclusively to direct displacement rather than conjugate addition, which we could prove by X-ray crystallography of 5. Moreover, the synthesis, spectroscopic data and crystal structures of important intermediates to the starting alkynyl difluoro terphenyl silane 2 are presented.     

Cone Dependence—A Basic Combinatorial Concept

We call A ? $ \mathbb{E} $ ⁿ cone independent of B ? $ \mathbb{E} $ ⁿ , the euclidean n-space, if no a = (a ₁,..., a _n ) ∈ A equals a linear combination of B \ {a} with non-negative coefficients. If A is cone independent of A we call A a cone independent set. We begin the analysis of this concept for the sets P(n) = {A ? {0, 1} ⁿ ? $ \mathbb{E} $ ⁿ : A is cone independent} and their maximal cardinalities c(n) ? max{|A| : A ∈ P(n)}. We show that lim _{n → ∞} $ \frac{{c\left( n \right)}}{{2^n }} $ > $\frac{1}{2}$ , but can't decide whether the limit equals 1. Furthermore, for integers 1 < k < ? ≤ n we prove first results about c _n (k, ?) ? max{|A| : A ∈ P _n (k, ?)}, where P _n (k, ?) = {A : A ? V ⁿ _k and V ⁿ _? is cone independent of A} and V ⁿ _k equals the set of binary sequences of length n and Hamming weight k. Finding c _n (k, ?) is in general a very hard problem with relations to finding Turan numbers.