The present invention provides a modified nucleic acid monomer compound having a specific backbone such as 2-ethylglycerol or methoxymethyl-1,3-propanediol backbone instead of a ribose or deoxyribose backbone of a nucleoside, and an oligonucleic acid analogue containing the monomer compound as at least one of building blocks. The oligonucleic acid analogue containing the nucleic acid monomer compound of the present invention allows provision of an oligonucleic acid analogue having excellent biological stability and/or target gene silencing activity.

The present invention relates to 2-Fluoro-b-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and/or adefovir resistant) and other mutant forms of these viruses, especially HBV.

The present invention relates to 2-Fluoro-b-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and/or adefovir resistant) and other mutant forms of these viruses, especially HBV.

The present invention relates to a substituted purine derivative of formula (1) wherein R.sup.1 is alkoxy or the like, R.sup.2 is alkyl or the like, Ring Q.sup.1 is aryl or the like, W.sup.1 is alkylene or the like, Ring Q.sup.2 is aromatic carbocyclyl or the like, n is 1-4, R.sup.3 is hydrogen atom or the like, X.sup.1 is single bond or the like, W.sup.2 is alkylene or the like, and R.sup.4 is hydrogen atom or the like, or a pharmaceutically acceptable salt thereof, which has a potent inhibitory effect against TLR7, and thereby is useful for treating autoimmune disease. ##STR00001##

The present invention relates to a substituted purine derivative of formula (1) wherein R.sup.1 is alkoxy or the like, R.sup.2 is alkyl or the like, Ring Q.sup.1 is aryl or the like, W.sup.1 is alkylene or the like, Ring Q.sup.2 is aromatic carbocyclyl or the like, n is 1-4, R.sup.3 is hydrogen atom or the like, X.sup.1 is single bond or the like, W.sup.2 is alkylene or the like, and R.sup.4 is hydrogen atom or the like, or a pharmaceutically acceptable salt thereof, which has a potent inhibitory effect against TLR7, and thereby is useful for treating autoimmune disease. ##STR00001##

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 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.

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (NO.sub.2), a halogen atom, a cyano group (CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##