The invention relates to a solvent-free green ammoximation process based on membrane distribution with a procedure as: adding TS-1 catalyst and ketone into a reactor in advance; setting the stirring speed and reaction temperature; after reaching the set temperature, adding a certain amount of ammonia and hydrogen peroxide into a reaction solution, wherein the hydrogen peroxide is fed in a way of using membrane as a distributor, the ammonia is fed in a continuous or semi-continuous manner; oxime is produced upon the reaction. The advantages of the invention include the mild reaction conditions, high reacting efficiency, simple operation and environmentally-friendly process. And there is no need to add any solvent during the reaction process. During the ammoximation reaction, both the conversion rate of the ketone and the selectivity of the oxime can be over 98.0%.

The present invention provides an improved process for the preparation of exametazime, which is used as ligand in preparation of technetium-99m complex. ##STR00001##

The present invention provides an improved process for the preparation of exametazime, which is used as ligand in preparation of technetium-99m complex. ##STR00001##

There is disclosed a process for the co-production of long chain -amino acid and long chain dibasic acid, comprising: (1) reacting long chain ketoacid derivative with hydroxylamine or subjecting ketoacid derivative to an ammoximation to yield oxime derivative; (2) subjecting oxime derivative to Beckmann rearrangement to yield a mixture of mixed amide derivatives; (3) hydrolyzing the mixed amide derivatives to produce long chain -amino acid and long chain dibasic acid.

There is disclosed a process for the co-production of long chain -amino acid and long chain dibasic acid, comprising: (1) reacting long chain ketoacid derivative with hydroxylamine or subjecting ketoacid derivative to an ammoximation to yield oxime derivative; (2) subjecting oxime derivative to Beckmann rearrangement to yield a mixture of mixed amide derivatives; (3) hydrolyzing the mixed amide derivatives to produce long chain -amino acid and long chain dibasic acid.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure ##STR00001##
wherein: R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure ##STR00001##
wherein: R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is OH or OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.