Asymmetric 1,3-Dipolar Cycloaddition Reactions

Stereochemical Control in Organic-Synthesis Using Silicon-Containing Compounds

2′-deoxy-2′-alkylnucleotides useful for stabilizing enzymatic nucleic acid molecules and antisense molecules.

2'-deoxy-2'alkylnucleotide containing nucleic acid

Insofar as one of the fundamental objectives of organic synthesis is the construction of complex molecules from simpler ones, the importance of synthetic efficiency becomes immediately apparent and has been well-recognized.1 The increase in molecular complexity2 that necessarily accompanies the course of a synthesis provides a guide (and a measure) of synthetic efficiency. As a goal, one would like to optimally match the change in molecular complexity at each step with reactions of comparable synthetic complexity. Thus, the creation of many bonds, rings, and stereocenters in a single transformation is a necessary (though not sufficient) condition for high synthetic efficiency. The ultimate, perfect match would constitute single-step syntheses. More realistically, especially in view of the desire for general synthetic methods, the combination of mulScott E. Denmark was born in New York in 1953. He obtained an S.B. degree from MIT in 1975 and carried out research with Daniel Kemp and Richard Holm. His graduate studies at the ETH-Zurich with Albert Eschenmoser culminated with the D. Sc. Tech. degree in 1980. That same year he joined the faculty of the University of Illinois at UrbanasChampaign and was promoted to full professor in 1987. In 1991 he was named the Reynold C. Fuson Professor of Chemistry. His research interests are primarily in the invention of new synthetic reactions, structure and reactivity of organoelement reagents, and the origin of stereocontrol in fundamental carbon−carbon bond forming reactions.

Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes.

Complete Basis Set and Gaussian-n methods were combined with CPCM continuum solvation methods to calculate pKa values for six carboxylic acids. An experimental value of −264.61 kcal/mol for the free energy of solvation of H+, ΔGs(H+), was combined with a value for Ggas(H+) of −6.28 kcal/mol to calculate pKa values with Cycle 1. The Complete Basis Set gas-phase methods used to calculate gas-phase free energies are very accurate, with mean unsigned errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM solvation calculations used to calculate condensed-phase free energies are slightly less accurate than the gas-phase models, and the best method has a mean unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. The use of Cycle 1 and the Complete Basis Set models combined with the CPCM solvation methods yielded pKa values accurate to less than half a pKa unit.

Accurate pKa Calculations for Carboxylic Acids Using Complete Basis Set and Gaussian-n Models Combined with CPCM Continuum Solvation Methods

A new seven-parameter Karplus-type relation between vicinal proton−fluorine coupling constants and the corresponding H−C−C−F torsion angles has been developed. The optimum values of the seven parameters were determined using a data set consisting of 57 3JHF values and the corresponding ΦHF torsion angles (ranging from cis, gauche, and trans regions) based upon ab initio structures as well as on the conformational analysis of temperature-dependent 3JHH of monofluorinated nucleosides 1−11, which were also complemented with the data from conformationally fixed compounds 12−22. The best fit generalized Karplus-type equation shows the difference between input and back-calculated 3JHF below 2.9 Hz with the overall rms deviation of 1.38 Hz, amounting to a total of 4% error for transoid coupling of ≈40−46 Hz, which compares very well with about 5% error encountered earlier in the experimental and the back-calculated 3JHH of 8−9 Hz in the latest Karplus−Altona equation (ref 14). This is the first use of a new Karp...

http://www.boc.uu.se/boc14www/publications/old/280.pdf

A New Generalized Karplus-Type Equation Relating Vicinal Proton-Fluorine Coupling Constants to H−C−C−F Torsion Angles

The distinct conformational preferences observed for the pentofuranosyl moieties in various 3'-substituted 2',3'-dideoxythymidine derivatives are closely related to the strength of the 3'-gauche effect, which is directly dictated by the electronegativity of the 3'-substituent. The efficiency of the 3'-gauche effect can now be quantitatively calculated with the help of simple linear calibration curves that correlate the gauche effect enthalpy AH^^") and the group electronegativity (x) of the 3'-substituent.

http://www.boc.uu.se/boc14www/publications/231.pdf

How Does the Electronegativity of the Substituent Dictate the Strength of the Gauche Effect

The anomeric and the gauche effects are two competing stereoelectronic forces that drive the North (N) (C2‘-exo-C3‘-endo) ⇄ South (S) (C2‘-endo-C3‘-exo) pseudorotational equilibrium in nucleosides. The quantitation of the energetics of pD dependent N ⇄ S pseudorotational equilibria of the pentofuranose moiety in 2‘-deoxyribonucleosides 1−6, 1‘-imidazolyl-2‘-deoxy-β-d-ribofuranose 7, and ribonucleosides 8−13 shows that the strength of the anomeric effect of the constituent heterocyclic moiety at C1‘ is dependent upon the unique aromatic nature of the nucleobase, which is tuned by the pD of the medium. The force that drives the protonation ⇄ deprotonation equilibrium of the heterocyclic nucleobases in nucleosides is transmitted through the anomeric effect to drive the two-state N ⇄ S pseudorotational equilibrium of the constituent furanose:  (i) The enhanced strength (ΔΔH°(P-N)) of the anomeric effect in the protonated (P) nucleoside compared to the neutral (N) form is experimentally evidenced by the increa...

Quantitation of the pD Dependent Thermodynamics of the N ⇄ S Pseudorotational Equilibrium of the Pentofuranose Moiety in Nucleosides Gives a Direct Measurement of the Strength of the Tunable Anomeric Effect and the pKa of the Nucleobase†

http://www.boc.uu.se/boc14www/publications/old/199.pdf

New stereocontrolled synthesis of isomeric C-branched-β-D nucleosides by intramolecular free-radical cyclization-opening reactions based on temporary silicon connection

http://www.boc.uu.se/boc14www/publications/199.pdf

Structural analysis of 2′,3′-dideoxyinosine, 2′,3′-dideoxyadenosine, 2′,3′-dideoxyguanosine and 2′,3′-dideoxycytidine by 500-MHz 1H-NMR spectroscopy and ab-initio molecul orbital calculations

J. Plavec

Papers

A New Generalized Karplus-Type Equation Relating Vicinal Proton-Fluorine Coupling Constants to H−C−C−F Torsion Angles

How Does the Electronegativity of the Substituent Dictate the Strength of the Gauche Effect

Quantitation of the pD Dependent Thermodynamics of the N ⇄ S Pseudorotational Equilibrium of the Pentofuranose Moiety in Nucleosides Gives a Direct Measurement of the Strength of the Tunable Anomeric Effect and the pKa of the Nucleobase†

New stereocontrolled synthesis of isomeric C-branched-β-D nucleosides by intramolecular free-radical cyclization-opening reactions based on temporary silicon connection

Structural analysis of 2′,3′-dideoxyinosine, 2′,3′-dideoxyadenosine, 2′,3′-dideoxyguanosine and 2′,3′-dideoxycytidine by 500-MHz 1H-NMR spectroscopy and ab-initio molecul orbital calculations