US 10,377,788 B2Granted

Method for producing glycoside compounds

AssigneeBonac Corporation

InventorsEriko Aoki, Takashi Kinoshita, Akihiro Itoh, Tadaaki Ohgi

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Abstract

The invention provides a production method of a glycoside compound or a salt thereof, which includes subjecting a thioether compound and an alcohol compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid, and then distillation in the presence of at least one kind of additive selected from a sulfur-containing antioxidant and a maleimide group-containing compound to give a thioether compound and a step of subjecting a glycoside compound and a thioether compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid to give a glycoside compound. By this method, a phosphoramidite preferable for the production (synthesis) of a nucleic acid can be produced more efficiently at a high purity.

Claims20

Dependent claims

A method of producing a glycoside compound represented by the formula (I):

wherein R1 is a hydroxyl-protecting group;
R2a and R2b are the same or different and each is a hydrogen atom or a substituent;
R2c is a hydrogen atom, an electron-withdrawing group or a substituent optionally substituted by an electron-withdrawing group;
R2a and R2b optionally form a ring together with a nitrogen atom bonded thereto;
B is an atomic group having a nucleic acid base skeleton;
L1 is an alkylene group;
D1 is an electron-withdrawing group;
and m is a positive integer, or a salt thereof, comprising
a step of subjecting
a thioether compound represented by the formula (103):
wherein m is as defined above;
and R and R′ are the same or different and each is an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, a cycloalkyl group, a cycloalkenyl group, a cycloalkylalkyl group, a cycloalkenylalkyl group or an alkoxyalkyl group, and
an alcohol compound represented by the formula (105):
wherein each symbol is as defined above,
to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid, and then to distillation in the presence of at least one maleimide group-containing compound to give a thioether compound represented by the formula (104):
wherein each symbol is as defined above (Step 0);
and
a step of subjecting a glycoside compound represented by the formula (Ia):
wherein B is as defined above;
and X is a group represented by the following formula:
wherein n is 0 or 1;
and R1a-R1d are the same or different and each is a hydrogen atom, an alkyl group or an alkoxy group, and a thioether compound represented by the formula (104)
to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid to give a glycoside compound represented by the formula (Ib):
wherein each symbol is as defined above (Step 1).

21 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/563,841Filed 1 Apr 2016
Priority: JP 2015-0761702 Apr 2015
Published: US 2018/0079768 A122 Mar 2018
Granted: 13 Aug 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07H 13/00
Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or
C07H 1/00
Processes for the preparation of sugar derivatives
C07H 1/02
Processes for the preparation of sugar derivatives: phosphorylation
C07H 19/06
Heterocyclic radicals containing only nitrogen atoms as ring hetero atom: pyrimidine radicals