Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve radical coupling of 3'- and 5'-substituted or 5'- and 3'-subutituted nucleosidic synthons.

Backbone modified oligonucleotide analogs and preparation thereof through radical coupling

Good Partnership between Sulfur and Fluorine: Sulfur-Based Fluorination and Fluoroalkylation Reagents for Organic Synthesis

Levulinic acid (LA) can be produced cost effectively and in high yield from renewable feedstocks in a new industrial process. The technology is being demonstrated on a 1 ton/day scale at a facility in South Glens Falls, New York. Low cost LA can be used as a platform chemical for the production of a wide range of value-added products. This research has demonstrated that LA can be converted to methyltetrahydrofuran (MTHF), a solvent and fuel extender. MTHF is produced in >80% molar yield via a single stage catalytic hydrogenation process. A new preparation of δ-aminolevulinic acid (DALA), a broad spectrum herbicide, from LA has also been developed. Each step in this new process proceeds in high (>80%) yield and affords DALA (as the hydrochloride salt) in >90% purity, giving a process that could be commercially viable. LA is also being investigated as a starting material for the production of diphenolic acid (DPA), a direct replacement for bisphenol A.

Production of levulinic acid and use as a platform chemical for derived products

The development of new reactions that facilitate the creative and efficient synthesis of molecular structures with desirable properties continues to fascinate chemists. The test of a significant contribution is its acceptance over time by the scientific community. The B-alkyl Suzuki-Miyaura cross-coupling reaction appears to be one such reaction. Since its disclosure by Suzuki and Miyaura in 1986, this reaction has been an attractive solution to challenging synthetic problems.

The B-alkyl Suzuki-Miyaura cross-coupling reaction: Development, mechanistic study, and applications in natural product synthesis

The chemistry of lithium enolates is used to demonstrate that complex structures held together by noncovalent bonds (“supramolecules”) may dramatically influence the result of seemingly simple standard reactions of organic synthesis. Detailed structural data have been obtained by crystallographic investigations of numerous Li enolates and analogous derivatives. The most remarkable features of these structures are aggregation to give dimers, tetramers, and higher oligomers, complexation of the metal centers by solvent molecules and chelating ligands, and hydrogen-bond formation of weak acids such as secondary amines with the anionoid part of the enolates. The presence in nonpolar solvents of the same supramolecules has been established by NMR-spectroscopic, by osmometric, and by calorimetric measurements. The structures and the order of magnitude of the interactions have also been reproduced by ab-initio calculations. Most importantly, supramolecules may be product-forming species in synthetic reactions of Li enolates. A knowledge of the complex structures of Li enolates also improves our understanding of their reactivity. Thus, simple procedures have been developed to avoid complications caused by secondary amines, formed concomitantly with Li enolates by the common methods. Mixtures of achiral Li enolates and chiral Li amides can give rise to enantioselective reactions. Solubilization by LiX is observed, especially of multiply lithiated compounds. This effect is exploited for alkylations of N-methylglycine (sarcosine) CH2 groups in open-chain oligopeptides. Thus, the cyclic undecapeptide cyclosporine, a potent immunosuppressant, is converted into a THF-soluble hexalithio derivative (without epimerization of stereogenic centers) and alkylated by a variety of electrophiles in the presence of either excess lithiumdiisopropyl amide or of up to 30 equivalents of lithium chloride. Depending on the nature of the LiX additive, a new stereogenic center of (R) or (S) configuration is created in the peptide chain by this process. A structure-activity correlation in the series of cyclosporine derivatives thus available is discussed.

Structure and Reactivity of Lithium Enolates. From Pinacolone to Selective C‐Alkylations of Peptides. Difficulties and Opportunities Afforded by Complex Structures

Terminal difluoro olefin analogs of squalene are time-dependent inhibitors of squalene epoxidase

Acyclic stereoselection. Part 42. 1,4- and 1,5-Stereoselection by sequential aldol addition to a .alpha.,.beta.-unsaturated aldehydes followed by Claisen rearrangement. Application to total synthesis of the vitamin E side chain and the archaebacterial C40 diol

4',5'-Unsaturated-5'-fluoro adenosine nucleosides: potent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase

On etudie la stereochimie de l'addition d'enolates d'esters d'acide O-alkyllactique aux aldehydes

Acyclic stereoselection. 23. Lactaldehyde enolate equivalents

ACYCLIC STEREOSELECTION. 14. O-ALKYLLACTIC ACID ESTERS: REAGENTS FOR THE STEREOSELECTIVE CONSTRUCTION OF ERYTHRO- AND THREO-α-METHYL-α,β-DIHYDROXY CARBONYL COMPOUNDS

Jarvi Esa T

Papers

Terminal difluoro olefin analogs of squalene are time-dependent inhibitors of squalene epoxidase

Acyclic stereoselection. Part 42. 1,4- and 1,5-Stereoselection by sequential aldol addition to a .alpha.,.beta.-unsaturated aldehydes followed by Claisen rearrangement. Application to total synthesis of the vitamin E side chain and the archaebacterial C40 diol

4',5'-Unsaturated-5'-fluoro adenosine nucleosides: potent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase

Acyclic stereoselection. 23. Lactaldehyde enolate equivalents

ACYCLIC STEREOSELECTION. 14. O-ALKYLLACTIC ACID ESTERS: REAGENTS FOR THE STEREOSELECTIVE CONSTRUCTION OF ERYTHRO- AND THREO-α-METHYL-α,β-DIHYDROXY CARBONYL COMPOUNDS