The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Compounds which can be used as prodrugs, in particular nucleoside diphosphate and triphosphate prodrugs, and a method for producing these compounds. The aim is to provide improved di- and/or triphosphate prodrugs, in particular nucleotide or nucleotide analog prodrugs. This is achieved in one aspect by providing bioreversibly and asymmetrically masked di- and triphosphate compounds, in particular nucleoside diphosphate and nucleoside triphosphate compounds or the analogs thereof. The masking only occurs at the terminal phosphate, i.e. at the β- or γ-phosphate, whereas the masking of the internal phosphate is omitted.

The present invention is directed to Compounds of Formula (I) and salts thereof, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are defined above herein. The present invention is also directed to uses of the compounds of Formula (I) to add phosphoramidate groups onto organic alcohols.

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This disclosure relates to the use of uridine diphosphate (UDP) derivatives, salts and/or prodrugs thereof for the treatment of inflammatory conditions (e.g., psoriasis) and glaucoma, to prodrugs of UDP derivatives, compositions comprising therapeutically effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs for treating various disorders including, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma, and inflammatory conditions, e.g., psoriasis and rheumatoid arthritis.

Benzothiazole phosphonate analogs and methods of using the same to inhibit the activity of Amyloid Binding Alcohol Dehydrogenase and in the amelioration or treatment of Alzheimer's disease are provided.

Provided are methods for treating Orthomyxoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula I:

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wherein R.sup.2 is halogen. The compounds, compositions, and methods provided are particularly useful for the treatment of Human Influenza virus infections.

Disclosed herein are compositions and methods for generating ribo-nucleic neutral (RNN) or deoxyribo-nucleic-neutral (DNN) polynucleotides with reduced anionic charge, for improved intracellular delivery. Also disclosed herein are methods of using RNN and DNN compositions.

Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

Provided is an oligonucleic acid analog which contains, as at least one structural unit thereof, a modified nucleic acid monomer compound which is a ring-open nucleoside having a cleaved carbon-carbon bond between the 2′ and 3′ positions and a substituent hydroxymethyl group at the 4′ position. When used as siRNA, the oligonucleic acid analog exhibits superior biological stability and target gene expression inhibiting activity. The oligonucleic acid analog can be used in antisense methods, ribozyme methods, and decoy methods, etc., can be used as a nucleic acid aptamer, and can also be used as a nucleic acid probe or molecular beacon, etc., or in genetic diagnostics, etc.

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

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