The Conservation of Orbital Symmetry

Die Erhaltung der Orbitalsymmetrie

Ever since the world-shaping discovery of penicillin, nature's molecular diversity has been extensively screened for new medications and lead compounds in drug discovery. The search for agents intended to combat infectious diseases has been of particular interest and has enjoyed a high degree of success. Indeed, the history of antibiotics is marked with impressive discoveries and drug-development stories, the overwhelming majority of which have their origin in natural products. Chemistry, and in particular chemical synthesis, has played a major role in bringing naturally occurring antibiotics and their derivatives to the clinic, and no doubt these disciplines will continue to be key enabling technologies. In this review article, we highlight a number of recent discoveries and advances in the chemistry, biology, and medicine of naturally occurring antibiotics, with particular emphasis on total synthesis, analogue design, and biological evaluation of molecules with novel mechanisms of action.

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Recent advances in the chemistry and biology of naturally occurring antibiotics.

Monosubstituted cyclopentadienyl half-sandwich transition metal complexes

Cationic oxazaborolidine 2 affords Diels−Alder adducts of ethyl acrylate and 2-substituted cyclopentadienes, derived from the corresponding mixture of regioisomers, as single isomers in excellent yields and enantioselectivities. Furthermore, Diels−Alder adducts of 1-substituted cyclopentadienes are obtained through a one-pot procedure whereby ethyl acrylate is initially employed to consume all 2-substituted cyclopentadiene. Subsequently, various 2,5-disubstituted benzoquinones are added to react with remaining 1-substituted cyclopentadiene. Remarkably, reaction occurs selectively at the double bond coordinated anti to catalyst 2 to provide adducts containing adjacent all-carbon quaternary stereocenters in high yields and excellent enantioselectivities.

Regioselective and Asymmetric Diels−Alder Reaction of 1- and 2-Substituted Cyclopentadienes Catalyzed by a Brønsted Acid Activated Chiral Oxazaborolidine

Some general characteristic properties of substituted cyclopentadienes

1.

On the basis of the behavior of methylcyclopentadiene it was confirmed that a characteristic feature of substituted cyclopentadienes is the occurrence of thermodynamic equilibrium between isomers differing in the positions of the intracycle double bonds.




2.

The equilibrium transformations of substituted cyclopentadienes have a stagewise character, i.e. the proton migrates from the methylene group (the 5-position) and goes predominatly to the adjacent C atom.




3.

The course of the alkylation of metal derivatives of cyclopentadiene was elucidated for the first time: it was proved that the primary reaction product is the 5-isomer, which in the process of the establishment: of equilibrium is converted into the 1-isomer, and then into an equilibrium mixture of 1- and 2-substituted cyclopentadienes.




4.

Samples of all three possible methylcyclopentadienes, each almost homogeneous in isomeric composition, were prepared. They were characterized by their individual adducts with maleic anhydride and by some derivatives of these. The mixture of adducts obtained from the equilibrium mixture of cyclopentadienes was separated via their esters.




5.

The rate of diene condensation with an active dienophile is very much greater than the rates of the isomeric transformations of methylcyclopentadienes.

Substituted cyclopent adienes and related compounds

1.

For the case of vic-trimethylcyclopentadienes it was confirmed that for substituted cyclopentadienes thermodynamic equilibrium exists between the isomers with respect to the intracycle double bonds and that the mutual transformations of the isomers have a stepwise character. In the equilibrium state vic-trimethylcyclopentadiene consists of almost homogeneous 1,2,3-isomer (about 95%) and contains only a small amount of 1,2,5- and 1,4,5-trimethylcyclopentadienes.




2.

A mixture of 1,2,5- and 1,4,5-trimethylcyclopentadienes was prepared, and the establishment of equilibrium concentrations of trimethylcyclopentadienes at 85–100° was observed for this sample.




3.

Each of the three isomeric vic-trimethylcyclopentadienes was characterized by pure crystalline derivatives.

Substituted cyclopentadienes and related compounds Communication 11. 1,2,3-trimethylcyclopentadiene

Some anomalies in the intensities of the bands of the C=C and C=O bonds in the vibrational spectra of α, β-unsaturated ketones have been explained by a difference in the sequence of the frequencies of the in-phase (νs) and out-of-phase (νas) vibrations of the multiple bonds in their cis (νs νas) arrangements.

Some anomalies in the vibrational spectra of α, β-unsaturated ketones

1.

The degree of substitution of the double bond in the bicyclo-(2,2,1)-heptene ring can be unambiguously established from a consideration of the Raman and IR absorption spectra in the region of 1570–1660 cm−1 [ν(C=C)] and 3000–3150 cm−1 [ν(C-H)].




2.

The structure of the adducts of methyl-substituted cyclopentadienes in each of the cases investigated corresponds to the structure of the initial dienes (including samples of dienes far from the equilibrium state, i. e., the rate of interaction of substituted cyclopentadienes with an active dienophile (maleic anhydride) far exceeds the rate of the equilibrium transformations.

Substituted cyclopentadienes and related compounds Communication 14. Peculiarities of the vibrational spectra of adducts of substituted cyclopentadienes with maleic anhydride

E. V. Sobolev

Papers

Some general characteristic properties of substituted cyclopentadienes

Substituted cyclopent adienes and related compounds

Substituted cyclopentadienes and related compounds Communication 11. 1,2,3-trimethylcyclopentadiene

Some anomalies in the vibrational spectra of α, β-unsaturated ketones

Substituted cyclopentadienes and related compounds Communication 14. Peculiarities of the vibrational spectra of adducts of substituted cyclopentadienes with maleic anhydride