Disclosed herein are methods for preparing [(2S,3R)N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide (compound G): and precursors thereof. ##STR00001##

The object of the present invention is to provide an industrial and economical process for preparing (E2)-cis-6,7-epoxy-2-nonenal of the following formula (3): ##STR00001## The present invention provides a process for preparing (E2)-cis-6,7-epoxy-2-nonenal (3), comprising at least steps of: subjecting (Z3,Z6)-3,6-nonadien-1-ol of the following formula (1) to oxidation: ##STR00002##
to form (E2,Z6)-2,6-nonadienal of the following formula (2); and ##STR00003## epoxidizing the resulting (E2,Z6)-2,6-nonadienal to form the aforesaid (E2)-cis-6,7-epoxy-2-nonenal (3).

The disclosure relates to an entecavir intermediate, a synthetic method therefor, and the synthetic method for entecavir by using the intermediate. According to the disclosure, the synthetic methods for entecavir and the intermediate thereof have the advantages of being controllable in chirality, high in yield and product purity, wide in source of raw materials, cheap and available in reagents, simple in reactions, convenient to operate, environmentally friendly, and suitable for industrial amplification production.

The disclosure relates to an entecavir intermediate, a synthetic method therefor, and the synthetic method for entecavir by using the intermediate. According to the disclosure, the synthetic methods for entecavir and the intermediate thereof have the advantages of being controllable in chirality, high in yield and product purity, wide in source of raw materials, cheap and available in reagents, simple in reactions, convenient to operate, environmentally friendly, and suitable for industrial amplification production.

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X):

##STR00001##

and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X):

##STR00001##

and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.

The proteasome inhibitors of this invention include peptide-based compounds with a short linear sequence of amino acids. An oxo or thio group is attached to the N-terminal amino acid. A protein-reactive electrophilic group such as an epoxyketone, an aziridinylketone, or a beta-lactone is attached to the C-terminal amino acid. Upon contact with a proteasome complex in a target cell, the electrophilic group reacts with a functional group in or near a binding pocket or active site of the proteasome, forming a covalent bond and thereby inactivating the proteasome. These and other proteasome inhibitors can be screened for binding affinity and an ability to selectively eliminate senescent cells or cancer cells. Compounds that selectively remove senescent cells can be developed for the treatment of conditions such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis.

The proteasome inhibitors of this invention include peptide-based compounds with a short linear sequence of amino acids. An oxo or thio group is attached to the N-terminal amino acid. A protein-reactive electrophilic group such as an epoxyketone, an aziridinylketone, or a beta-lactone is attached to the C-terminal amino acid. Upon contact with a proteasome complex in a target cell, the electrophilic group reacts with a functional group in or near a binding pocket or active site of the proteasome, forming a covalent bond and thereby inactivating the proteasome. These and other proteasome inhibitors can be screened for binding affinity and an ability to selectively eliminate senescent cells or cancer cells. Compounds that selectively remove senescent cells can be developed for the treatment of conditions such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis.

The present invention relates to tiglien-3-one compounds and their use in methods of treating or preventing protozoal infections, bacterial infections, parasitic infections and cell proliferative disorders. The tiglien-3-one compounds are also used in methods of controlling pests in humans, animals, plants and the environment

The present invention relates to tiglien-3-one compounds and their use in methods of treating or preventing protozoal infections, bacterial infections, parasitic infections and cell proliferative disorders. The tiglien-3-one compounds are also used in methods of controlling pests in humans, animals, plants and the environment