This invention is intended to discover a novel solvent that can be used as an alternative to toluene in the step of deprotection in the method of solid-phase nucleic acid synthesis. With the use of such novel solvent, various problems caused by the use of toluene are dissolved. This invention is also intended to provide a method of solid-phase nucleic acid synthesis in which protected nucleoside phosphoramidites in which a protective group is bonded to a hydroxyl group at the 5′position or the 3′ position of a nucleoside are sequentially bound on a solid phase carrier, where a reaction of removing the protecting group from the protected nucleoside phosphoramidite is carried out in a solution comprising an acid with a pKa of 0.2 to 0.8 and acetonitrile.

Provided is a drug containing a liver targeting specific ligand and a thyroid hormone receptor agonist in its structure, which is a new drug structure formed by linking the liver targeting specific ligand with the thyroid hormone receptor agonist through a branched chain, a linker and a linking chain. Thyroid hormone receptors (TRs) are divided into two subtypes, TR-α and TR-β, wherein, TR-β is mainly expressed in liver, and TR-α is mainly expressed in heart, nervous system, etc. In certain embodiments, it is envisaged that the provided drug has the action of liver targeting, can specifically bring the thyroid hormone receptor agonist into liver, without entering heart and other issues, and may thereby avoid side effects caused by the action of the thyroid hormone receptor agonist on other issues, and maintain its therapeutic efficacy in the treatment of lipid metabolism disorders and related complications.

The invention provides a method for the cleavage of Fmoc group characterized by using a solution comprising 3-(diethylamino)propylamine. In particular, it provides a method for the preparation of peptides in solid phase wherein Fmoc protected amino acids are used and the Fmoc group is cleaved by a solution comprising 3-(diethylamino)propylamine.

Provided a polymerizable compound represented by the following Formula A-1 or Formula A-2: In Formula A-1 or Formula A-2, R.sup.1 represents an electron-donating group; n represents an integer from 1 to 5; R.sup.2 represents a hydrogen atom, a halogen atom, or —OR.sup.O, wherein R.sup.O represents a hydrogen atom, an alkyl group, or a protecting group of a hydroxy group; R.sup.3 represents a hydrogen atom or a protecting group of a hydroxy group; and X represents a structure represented by any one of Formula B-1 to Formula B-5.

Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

Provided is an alkyldiphenylmethane protective agent, which can prevent solidification or insolubilization of a compound by protecting a functional group of the compound to achieve easy separation and purification after a reaction. An alkyldiphenylmethane compound represented by general formula (1): ##STR00001## wherein Y represents —OR.sup.19 (wherein R.sup.19 represents a hydrogen atom or an active ester-type protecting group), —NHR.sup.20 (wherein R.sup.20 represents a hydrogen atom, a C.sub.1-6 linear or branched alkyl group, or an aralkyl group), isocyanate group, an azide group, or a halogen atom, Z represents a C.sub.1-4 linear or branched alkyl group, an alkenyl group, or a cycloalkyl group, at least one of R.sup.1 to R.sup.10 represents a group represented by formula (2):
—O—R.sup.11—X-A  (2) and the others each independently represent a hydrogen atom, a halogen atom, a C.sub.1-4 alkyl group, or a C.sub.1-4 alkoxy group; R.sup.11 represents a C.sub.1-16 linear or branched alkylene group; X represents O or CONR.sup.21 (wherein R.sup.21 represents a hydrogen atom or a C.sub.1-4 alkyl group); and A represents, for example, a group represented by formula (3): ##STR00002## wherein R.sup.12, R.sup.13, and R.sup.14 may be the same or different and each independently represent a C.sub.1-6 linear or branched alkyl group or an optionally substituted aryl group; R.sup.15 represents a single bond or a C.sub.1-3 linear or branched alkylene group; and R.sup.16, R.sup.17, and R.sup.18 each independently represent a C.sub.1-3 linear or branched alkylene group.

Provided are a peptide borate ester compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, and pharmaceutical use thereof. The peptide borate ester compound or pharmaceutically acceptable salt thereof has a structure as shown in Formula (I), and is useful in the preparation of proteasome inhibitors to treat solid tumors and hematoma.

The invention relates to a new process for the purification of oligonucleotides which comprises the removal of an acid labile 5′hydroxy protecting group at the 5′-O-oligonucleotide terminus of the oligonucleotide by means of an on-column de-protection with an acid.

The invention relates to methods of synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine with increased purity and uniform particle size distribution. In particular, methods of the invention include crystallization and isolation procedures rendering synthetic reaction intermediates. The invention further includes compositions comprising the final compound in highly pure form, including lower number of impurities and lower levels of individual and total impurities.

The present invention provides a production method suitable for industrial production of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position.

The present invention is a method for producing N-[(4-methylphenyl)sulfonyl]-L-phenylalanine salt of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position, which comprises Step 2: a step of subjecting 2-(3-bromo-2-fluorobenzyl)-3-(methoxyimino)pyrrolidine having a protecting group at the 1-position to a reduction reaction; and Step 3: a step of subjecting the product obtained in Step 2 to optical resolution using salt formation with N-[(4-methylphenyl)sulfonyl]-L-phenylalanine.