Solanum-alkaloide—SCVI: Synthese von solafloridin und 25-iso-solafloridin

3β,16α-Diacetoxy-20-(5-methyl-2-pyridyl)-pregna-5,20-diene (2) available from 3β-acetoxy-pregna-5,16-dien-20-one (1) was transformed into solafloridine (11) and 25-iso-solafloridine (13).     

Test of the information theory of branching ratios by classical trajectory computations

Extensive classical trajectory calculations are reported for the system F + HD → HF + D or DF + H, over a wide variety of initial conditions. The results of these computations are used to assess the utility of the information theoretic approach to the prediction of the initial-state dependence of the branching ratio, Γ_HF/DF. Two distinct forms for the information theoretic branching ratio are considered, corresponding to two different choices of constraints upon the transition probability matrix. The constraints in question are the “model” constraint employed by Kaplan and Levine, and the “direct” constraint, a generalisation of that introduced by Levine and Kosloff. The two forms of information theory give satisfactory predictions under selected (differing) initial conditions. Neither form is clearly superior. In particular, both fail to predict the observed trend of Γ_HF/DF with initial rotational state J, for the case of thermally averaged initial translational energies. This failure is linked to an important “interbranch constraint” not incorporated in the theory, stemming from the different activation energies for formation of the two products.     

Tertiary contact formation in alpha-synuclein probed by electron transfer

To explore tertiary contact formation in alpha-synuclein, a natively unfolded protein implicated in Parkinson's disease, we have measured the rates of reaction between a powerful electron donor, the tryptophan (W) triplet excited state, and an acceptor, 3-nitro-tyrosine (Y(NO2)) in six different variants, probing loop sizes between 15 and 132 residues. Electron transfer rates decrease with loop size with the fastest contact time of 140 ns for the N-terminal pair and the slowest of 1.2 mus for the N- to C-terminal pair. Diffusion coefficients ranging from approximately 2 x 10-6 to approximately 10-5 cm2 s-1 were extracted from simultaneous fits of the W to Y(NO2) electron (triplet excited state) and energy transfer (singlet excited state) kinetics.     

Die mehrstellenformeln für den Laplaceoperator

Summary Difference methods for the numerical solution of linear partial differential equations may often be improved by using a weighted right hand side instead of the original right hand side of the differential equation. Difference formulas, for which that is possible, are called Mehrstellenformeln or Hermitian formulas. In this paper the Hermitian formulas for the approximation of Laplace's operator are characterized by a very simple condition. We prove, that in two-dimensional case for a Hermitian formula of ordern at leastn+3 discretization points are necessary. We give examples of such optimal formulas of arbitrary high-order.

     

Isobutane chemical ionization mass spectra of unsaturated alcohols

Analysis of the isobutane chemical ionization mass spectra of hexenols, cyclohexenols and various syn/anti pairs of bicyclic and tricyclic homoallylic alcohols shows that: (i) the spectra of the allylic alcohols are dominated by [M + H – H₂O]⁺ and [M + C₄H₉–H₂O]⁺ ions and contain traces of [M + H]⁺ ions; (ii) [M + H]⁺ ions are prominent in the spectra of acyclic and certain cyclic homoallylic alcohols; and (iii) [M + H]⁺ ions dominate the spectra of other acyclic unsaturated alcohols. The [M + H]⁺ ions may result from either: (a) protonation of the hydroxyl group, followed by a very rapid intramolecular proton transfer from the protonated hydroxyl group to the carbon–carbon double bond or internal solvation of the protonated hydroxyl group by the carbon–carbon double bond; and/or (b) direct protonation of the carbon–carbon double bond with significant internal solvation of the resulting carbocation by the hydroxyl group, which may lead to carbon–oxygen bond formation to give a protonated cyclic ether. The consequences of placing various geometric constraints on the possible intramolecular interactions between the hydroxyl group and the carbon–carbon double bond in unsaturated alcohols are explored.     

Stripping voltammetry of copper and lead using gold electrodes modified with self-assembled monolayers

One problem associated with using bare solid metal electrodes, such as gold and platinum, in stripping analysis to determine heavy metal ions such as lead and copper ions in dilute solutions is that underpotential deposition (UPD) gives multiple stripping peaks in the analysis of mixtures. These peaks are often overlapped and cannot be conveniently used for analytical purposes. Bifunctional alkylthiols, such as 3-mercaptopropionic acid, with an ionizable group on the other terminal end of the thiol can form self-assembled monolayers (SAMs) on the surface of the gold electrode. It is shown that such an SAM-modified gold electrode minimizes the UPD effects for the stripping analysis of lead and copper. The anodic peak potential shifts and the peak shape changes, indicating that the SAM changes the deposition and stripping steps of these heavy metal ions. Thus, the sensitivity levels for both single species and mixtures can be significantly improved for the conventional solid electrodes. The mechanism of the deposition reaction at the SAM-modified gold electrodes is discussed. Received: 29 May 1997 / Accepted: 24 June 1997     

Molecular orbital calculations of ring opening of the isoelectronic cyclopropylcarbinyl radical, cyclopropoxy radical, and cyclopropylaminium radical cation series of radical clocks

Detailed molecular orbital calculations were directed to the cyclopropylcarbinyl radical (1), the cyclopropoxy radical (2), and the cyclopropylaminium radical cation (3) as well as their ring-opened products. Since a considerable amount of data are published about cyclopropylcarbinyl radicals, calculations were made for this species and related ring-opened products as a reference for 2 and 3 and their reactions. Radicals 1-3 have practical utility as "radical clocks" that can be used to time other radical reactions. Radical 3 is of further interest in photoelectron-transfer processes where the back-electron-transfer process may be suppressed by rapid ring opening. Calculations have been carried out at the UHF/6-31G*, MP4//MP2/6-31G*, DFT B3LYP/6-31G*, and CCSD(T)/cc-pVTZ//QCISD/cc-pVDZ levels. Energies are corrected to 298 K, and the barriers between species are reported in terms of Arrhenius E(a) and log A values along with differences in enthalpies, free energies, and entropies. The CCSD(T)-calculated energy barrier for ring opening of 1 is E(a) = 9.70, DeltaG* = 8.49 kcal/mol, which compares favorably to the previously calculated value of E(a) = 9.53 kcal/mol by the G2 method, but is higher than an experimental value of 7.05 kcal/mol. Our CCSD(T)-calculated E(a) value is also higher by 1.8 kcal/mol than a previously reported CBS-RAD//B3LYP/6-31G* calculation. The cyclopropoxy radical has a very small barrier to ring opening (CCSD(T), E(a) = 0.64 kcal/mol) and should be a very sensitive time clock. Of the three series studied, the cyclopropylaminium radical cation is most complex. In agreement with experimental data, bisected cyclopropylaminium radical cation is not found, but instead a ring-opened species is found. A perpendicular cyclopropylaminium radical cation (4) was found as a transition-state structure. Rotation of the 2p orbital in 4 to the bisected array results in ring opening. The minimum onset energy of photoionization of cyclopropylamine was calculated to be 201.5 kcal/mol (CCSD(T)) compared to experimental values of between about 201 and 204 kcal/mol. Calculations were made on the closely related cyclopropylcarbinyl and bicyclobutonium cations. Stabilization of the bisected cyclopropylcarbinyl conformer relative to the perpendicular species is much greater for the cations (29.1 kcal/ mol, QCISD) compared to the radicals (3.10 kcal/mol, QCISD). A search was made for analogues to the bicyclobutonium cation in the radical series 1 and 2 and the radical cation series 3. No comparable species were found. A rationale was made for some conflicting calculations involving the cyclopropylcarbinyl and bicyclobutonium cations. The order of stability of the cyclopropyl-X radicals was calculated to be X = CH2 > X = O > X = NH2+, where the latter species has no barrier for ring opening. The relative rate of ring opening for cyclopropyl-X radicals X = CH2 to X = O was calculated to be 3.1 x 10(6) s(-1) at 298 K (QCISD).     

Investigation of a stereoselective co-mediated rearrangement reaction

A stereocontrolled approach to alpha-alkyl beta-alkynyl cyclohexanones is reported through a Lewis acid mediated rearrangement reaction of enol ethers bearing an Co-alkyne moiety. The reaction proceeds with high levels of stereoselectivity in the presence of Ti- and B-Lewis acids to provide a range of alpha,beta-disubstituted cyclohexanones in high yield although the products are prone to epimerization at the alpha-position in the presence of the B-promoter system. The potential for an enantioselective variant of this process is outlined, and a rationale for the observed stereochemical trends and detailed structural analyses of the ketone products are described.     

A planning strategy for diversity-oriented synthesis

In contrast to target-oriented synthesis (TOS) and medicinal or combinatorial chemistry, which aim to access precise or dense regions of chemistry space, diversity-oriented synthesis (DOS) populates chemical space broadly with small-molecules having diverse structures. The goals of DOS include the development of pathways leading to the efficient (three- to five-step) synthesis of collections of small molecules having skeletal and stereochemical diversity with defined coordinates in chemical space. Ideally, these pathways also yield compounds having the potential to attach appendages site- and stereoselectively to a variety of attachment sites during a post-screening, maturation stage. The diverse skeletons and stereochemistries ensure that the appendages can be positioned in multiple orientations about the surface of the molecules. TOS as well as medicinal and combinatorial chemistries have been advanced by the development of retrosynthetic analysis. Although the distinct goals of DOS do not permit the application of retrosynthetic concepts and thinking, these foundations are being built on, by using parallel logic, to develop a complementary procedure known as forward-synthetic analysis. This analysis facilitates synthetic planning, communication, and teaching in this evolving discipline.