The present invention provides compounds of formula (10), formula (12), formula (14) and formula (15) ##STR00001## wherein R, R.sup.1, R.sup.2, Cy.sup.1 and X are as described herein.

The present invention provides compounds of formula (10), formula (12), formula (14) and formula (15) ##STR00001## wherein R, R.sup.1, R.sup.2, Cy.sup.1 and X are as described herein.

Compounds having the formula I, II, or III:

##STR00001##

are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.

Compounds having the formula I, II, or III:

##STR00001##

are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.

The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

A method of increasing a density of carboxylic acids on a surface of a carbon nanoparticle is disclosed. The method includes contacting an oxygen-containing functional group on a surface of a carbon nanoparticle with a reducing agent to provide a hydroxyl group; reacting the hydroxyl group with a diazoacetate ester in the presence of a transition metal catalyst to provide an ester, the diazoacetate ester having the structure wherein R is a C1-8 hydrocarbyl, preferably tert-butyl, methyl, ethyl, isopropyl, allyl, benzyl, pentafluorophenyl, or N-succinimidyl; and cleaving the ester to provide a carboxylic acid group. Surface-functionalized carbon nanoparticles made by the method are also disclosed.

A method of increasing a density of carboxylic acids on a surface of a carbon nanoparticle is disclosed. The method includes contacting an oxygen-containing functional group on a surface of a carbon nanoparticle with a reducing agent to provide a hydroxyl group; reacting the hydroxyl group with a diazoacetate ester in the presence of a transition metal catalyst to provide an ester, the diazoacetate ester having the structure wherein R is a C1-8 hydrocarbyl, preferably tert-butyl, methyl, ethyl, isopropyl, allyl, benzyl, pentafluorophenyl, or N-succinimidyl; and cleaving the ester to provide a carboxylic acid group. Surface-functionalized carbon nanoparticles made by the method are also disclosed.

The invention provides xenonucleic acids and synthetic chimeric xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing crispr mediated genome editing efficiency. The invention also provides methods and compositions for inducing CRISPR/Cas-based gene editing/regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using single guide RNAs (sgRNAs) that have been chemically modified with xeno nucleic acids which enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a sgRNA that has been chemically modified with xeno nucleic acids to correct a mutation in a target gene associated with the genetic disease.

The invention provides xenonucleic acids and synthetic chimeric xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing crispr mediated genome editing efficiency. The invention also provides methods and compositions for inducing CRISPR/Cas-based gene editing/regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using single guide RNAs (sgRNAs) that have been chemically modified with xeno nucleic acids which enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a sgRNA that has been chemically modified with xeno nucleic acids to correct a mutation in a target gene associated with the genetic disease.