Ajinomoto Co., Ltd.

Naoko Hirose

Kunisuke Izawa

Tomoyuki Onishi

Takashi Nakano

Masakazu Nakazawa

Satoshi Katayama

Takayuki Suzuki

Satoshi Takamatsu

Daisuke Takahashi

Taisuke Ichimaru

Kunihiro Hirai

Yasuyuki Otake

Ken Yamashita

Tokumi Maruyama

Yuichi Suzuki

Yutaka Honda

Takayoshi Torii

Daigaku Hideura

Oligonucleotides may be produced by a process, including (1) condensing a nucleoside, nucleotide or oligonucleotide (b), and a nucleoside, nucleotide or oligonucleotide (a), or a substituted nucleotide or oligonucleotide (&#x3b1;) in a non-polar solvent to give a reaction solution containing a phosphite triester product (c); (3) oxidizing or sulfurizing the phosphite triester product (c) to give a reaction solution containing an oligonucleotide (d) wherein the 5'-hydroxy group is protected; (4) deprotecting the oligonucleotide (d) to give a reaction solution containing an oligonucleotide (e) wherein the 5&#x2032;-hydroxy group is not protected; and (6) adding a polar solvent to the reaction solution containing the oligonucleotide (e) and purifying the oligonucleotide (e) by solid-liquid separation, wherein said nucleoside, nucleotide or oligonucleotide (a) or said substituted nucleotide or oligonucleotide (&#x3b1;) is a compound represented by formula (a-i): wherein Base, R, R, m, L, Y, and Z are defined herein.

Oligonucleotide production method, and nucleoside, nucleotide, or oligonucleotide

Precipitation promoters, which are an organic compound having one or more linear aliphatic hydrocarbon groups having not less than 10 carbon atoms, wherein the aliphatic hydrocarbon group has not less than 20 carbon atoms in total are useful for precipitating an organic compound protected by an organic group having one or more aliphatic hydrocarbon groups having not less than 10 carbon atoms from a solvent.

Precipitation promoter and precipitation method in which same is used

Herein are disclosed a process for increasing in purity, or purifying, an N-protected-&#x3b2;-aminoalcohol which process comprises (i) adding water to a polar organic solvent in which an N-protected-&#x3b2;-aminoalcohol such as a (2R,3S)- or (2S,3R)-3-tert-butoxycarbonylamino-1-halo-2-hydroxy-4-phenylbutane or the like, or (ii) crystallizing such an N-protected-&#x3b2;-aminoalcohol from a diol or a diol-based mixed solvent, and a process for producing the corresponding N-protected-&#x3b2;-aminoepoxide which process comprises treating, with a base, the thus purity-enhanced N-protected-&#x3b2;-aminoalcohol. Such N-protected-&#x3b2;-aminoalcohols and N-protected-&#x3b2;-aminoepoxides are both useful as synthetic intermediates for medicine compounds, such as, e.g., HIV protease inhibitor and the like.

Processes for preparation of N-protected-&#x3b2;-amino alcohols and N-protected-&#x3b2;-amino epoxides

A process for producing &#x3b1;-aminohalomethyl ketones or N-protected &#x3b1;-aminohalomethyl ketones from specified 3-oxazolidin-5-one derivatives via 5-halomethyl-5-hydroxy-3-oxazolidine derivatives. By this process, &#x3b1;-aminohalomethyl ketones and compounds relating to them can be obtained efficiently and economically in industrial scale.

Process for producing &#x3b1;-aminoketones

Method for producing epoxide crystal

The present invention provides a production method including adding water to a solution of (2R,3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane ((2R,3S)-epoxide compound) or (2S,3R)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane ((2S,3R)-epoxide compound) in a polar solvent to allow crystallization, whereby to produce crystals of the (2R,3S)-epoxide compound or the (2S,3R)-epoxide compound conveniently in a high yield by an industrial production method without requiring an extremely low temperature.

Production method of epoxide crystal

A process for producing &agr;-aminohalomethyl ketones or N-protected &agr;-aminohalomethyl ketones from specified 3-oxazolidin-5-one derivatives via 5-halomethyl-5-hydroxy-3-oxazolidine derivatives. By this process, &agr;-aminohalomethyl ketones and compounds relating to them can be obtained efficiently and economically in industrial scale.

Process for producing &agr;-aminoketones

An amino group of an &agr;-amino acid ester is protected as an imine, and it is then reacted with a halomethyllithium to obtain an N-protected-&agr;-aminohalomethylketone. Further, this N-protected-&agr;-aminohalomethylketone is treated with an acid to obtain an &agr;-aminohalomethylketone. This process is suited for industrial production, and can produce an &agr;-aminohalomethylketone and its related compounds economically and efficiently.

A process for producing &agr;-amino-dihalogenated methyl ketone derivatives by reacting an N-protected &agr;-amino acid ester with a dihalomethyl lithium is provided. This process is suitable for the production on an industrial scale and by this process, &agr;-amino-dihalogenated methyl ketone derivatives and &bgr;-amino-&agr;-hydroxycarboxylic acid derivatives can be obtained efficiently and economically advantageously.

Process for producing &agr;-aminoketone derivatives

Process for producing 2&prime;,3&prime;-diethyl substituted nucleoside derivatives

Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3&prime;-position of the saccharide moiety is deoxylated, can be substituted at the 2&prime;-position at an extremely high yield. Specifically, by subjecting a 3&prime;-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2&prime;-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield. Methods for producing nucleoside derivatives including 9-(2,3-dideoxy-2-fluoro-&bgr;-D-threo-pentofuranosyl)adenine (FddA) and their related compounds, in a simplified manner, at a high yield and at low costs, and especially Economical methods for substituting substrates, of which the 3&prime;-position of the saccharide moiety is deoxylated, at the 2&prime;-position to produce those nucleoside derivatives on an industrial scale are also provided.

Methods for producing nucleoside derivatives and intermediates therefor

Process for producing alpha-aminoketones

Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3'-position of the saccharide moiety is deoxylated, can be substituted at the 2'-position at an extremely high yield. Specifically, by subjecting a 3'-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2'-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield. Methods for producing nucleoside derivatives including 9-(2,3-dideoxy-2-fluoro-.beta.-D-threo-pentofuranosyl)adenine (FddA) and their related compounds, in a simplified manner, at a high yield and at low costs, and especially Economical methods for substituting substrates, of which the 3'-position of the saccharide moiety is deoxylated, at the 2'-position to produce those nucleoside derivatives on an industrial scale are also provided.

Growing community of inventors

Kawasaki, Japan

Naoko Hirose