CA2184681A1 - Process for preparing substituted n-ethylglycine derivatives - Google Patents
Process for preparing substituted n-ethylglycine derivativesInfo
- Publication number
- CA2184681A1 CA2184681A1 CA002184681A CA2184681A CA2184681A1 CA 2184681 A1 CA2184681 A1 CA 2184681A1 CA 002184681 A CA002184681 A CA 002184681A CA 2184681 A CA2184681 A CA 2184681A CA 2184681 A1 CA2184681 A1 CA 2184681A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- protecting group
- labile
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
- C07K14/003—Peptide-nucleic acids (PNAs)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Process for preparing substituted N-ethylglycine derivatives Processes are described for preparing substituted N-ethylglycine derivatives of the formula in which PG is an amino protecting group which is labile towards weak acids and is of the urethane type or the trityl type, X is NH or O, and B' is bases which are customary in nucleotide chemistry and whose exocyclic amino and/or hydroxyl groups are protected by suitable known protecting groups, and the salts thereof. The process comprises reacting a compound of the formula in which R is hydrogen or, if X = NH, an acid-labile protecting group, and R1 is a protecting group which is labile towards acids and stable towards amines, and X is defined as above, with a compound of the formula at 0 - 45°C in a suitable solvent, using a coupling reagent which is customary in peptide chemistry, to give a compound of the formula and subsequently converting this compound, by means of eliminating the acid-labile ester protecting group R1 and, for X = NH, by means of simultaneously eliminating the acid-labile protecting group R, under suitable acidic conditions, in a suitable solvent, where appropriate with the addition of cation-capturing agents, into a compound of the formula
Claims (4)
1. A process for preparing substituted N-ethylglycine derivatives of the formula I
(I) in which PG is a labile amino protecting group which is labile towards weak acids and which is of the urethane type or the trityl type, X is NH or O, and B' is bases which are customary in nucleotide chemistry and whose exocyclic amino and/or hydroxyl groups are protected by suitable known protecting groups, and the salts thereof, which comprises a) reacting a compound of the formula II
(II), in which R is hydrogen or, if X = NH, an acid-labile protecting group, and R1 is a protecting group which is labile towards acids and stable towards amines, and X is defined as above, with a compound of the formula III
(III) in which B' is defined as above, at 0 - 45°C in a suitable solvent using a coupling reagent which is customary in peptide chemistry to give a compound of the formula IV
(IV) in which R, X, B' and R1 are defined as above, b) subsequently converting the compound of the formula IV, by means of eliminating the acid-labile ester protecting group R1 and, for X = NH, by means of simultaneously eliminating the acid-labile protecting group R
under suitable acidic conditions, in a suitable solvent, where appropriate with the addition of cation-capturing agents, into a compound of the formula V, with compounds of the formula IV in which X = O being, where appropriate, additionally treated with bases in aqueous medium, (V) in which X and B' are defined as above, c) converting the compound of the formula V, using a suitable reagent in a suitable solvent and using an auxiliary base, into the compound of the formula I and subsequently, where appropriate, converting the latter into its salts.
(I) in which PG is a labile amino protecting group which is labile towards weak acids and which is of the urethane type or the trityl type, X is NH or O, and B' is bases which are customary in nucleotide chemistry and whose exocyclic amino and/or hydroxyl groups are protected by suitable known protecting groups, and the salts thereof, which comprises a) reacting a compound of the formula II
(II), in which R is hydrogen or, if X = NH, an acid-labile protecting group, and R1 is a protecting group which is labile towards acids and stable towards amines, and X is defined as above, with a compound of the formula III
(III) in which B' is defined as above, at 0 - 45°C in a suitable solvent using a coupling reagent which is customary in peptide chemistry to give a compound of the formula IV
(IV) in which R, X, B' and R1 are defined as above, b) subsequently converting the compound of the formula IV, by means of eliminating the acid-labile ester protecting group R1 and, for X = NH, by means of simultaneously eliminating the acid-labile protecting group R
under suitable acidic conditions, in a suitable solvent, where appropriate with the addition of cation-capturing agents, into a compound of the formula V, with compounds of the formula IV in which X = O being, where appropriate, additionally treated with bases in aqueous medium, (V) in which X and B' are defined as above, c) converting the compound of the formula V, using a suitable reagent in a suitable solvent and using an auxiliary base, into the compound of the formula I and subsequently, where appropriate, converting the latter into its salts.
2. The process for preparing substituted N-ethylglycine derivatives of the formula I as claimed in claim 1, wherein a) a compound of the formula II, in which R is hydrogen, or, if X = NH, Boc, Ddz or Trt and R1 is tert-butyl or (2-chlorophenyl)diphenylmethyl, und X is defined as above, is reacted with a compound of the formula III, in which B' is defined above, at room temperature, in DMF, acetonitrile, dichloromethane or mixtures of these solvents, using carbodiimides, phosphonium reagents, uronium reagents, acid halides or activated esters, to give a compound of the formula IV
in which R, X, B' and R1 are defined as above, b) the compound of the formula IV is subsequently converted, by means of eliminating the acid-labile ester protecting group R1 and, for X =
NH, by means of simultaneously eliminating the acid-labile protecting group R with trifluoroacetic acid in dichloromethane, ethyl acetate or dioxane, where appropriate with the addition of anisole, thiophenol or triethylsilane, into a compound of the formula V, in which X and B' are defined as above, and with the compounds of the formula IV in which X = O being additionally treated, where appropriate, with NaOH or triethylamine in aqueous medium, c) the compound of the formula V is converted, with t-Bumeoc fluoride, Adpoc azide, Bpoc azide, Ddz-(phenyl)carbonate, Trt-Cl, Mtt-Cl, Mmt-Cl, Dmt-Cl or Pixyl-Cl in DMF, NMP, acetonitrile, dichloromethane or mixtures of these solvents, using NEM, DIPEA, pyridine or triethylamine, into the compound of the formula I and subsequently, where appropriate, into its salts.
in which R, X, B' and R1 are defined as above, b) the compound of the formula IV is subsequently converted, by means of eliminating the acid-labile ester protecting group R1 and, for X =
NH, by means of simultaneously eliminating the acid-labile protecting group R with trifluoroacetic acid in dichloromethane, ethyl acetate or dioxane, where appropriate with the addition of anisole, thiophenol or triethylsilane, into a compound of the formula V, in which X and B' are defined as above, and with the compounds of the formula IV in which X = O being additionally treated, where appropriate, with NaOH or triethylamine in aqueous medium, c) the compound of the formula V is converted, with t-Bumeoc fluoride, Adpoc azide, Bpoc azide, Ddz-(phenyl)carbonate, Trt-Cl, Mtt-Cl, Mmt-Cl, Dmt-Cl or Pixyl-Cl in DMF, NMP, acetonitrile, dichloromethane or mixtures of these solvents, using NEM, DIPEA, pyridine or triethylamine, into the compound of the formula I and subsequently, where appropriate, into its salts.
3. The process for preparing substituted N-ethylglycine derivatives of the formula I as claimed in claim 2, wherein, in the compound of the formula II, R is hydrogen or, if X = NH, Boc, and R1 is tert-butyl.
4. An intermediate of the formula IV, (IV) in which X is NH or O, B' is bases which are customary in nucleotide chemistry and whose exocyclic amino and/or hydroxyl groups are protected by suitable known protecting groups, R is hydrogen or, if X = NH, an acid-labile protecting group, and R1 is a protecting group which is labile towards acids and stable towards amines.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19532553.2 | 1995-09-04 | ||
DE19532553A DE19532553A1 (en) | 1995-09-04 | 1995-09-04 | Process for the preparation of substituted N-ethyl-glycine derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2184681A1 true CA2184681A1 (en) | 1997-03-05 |
CA2184681C CA2184681C (en) | 2010-01-05 |
Family
ID=7771182
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002184681A Expired - Fee Related CA2184681C (en) | 1995-09-04 | 1996-09-03 | Process for preparing substituted n-ethylglycine derivatives |
Country Status (11)
Country | Link |
---|---|
US (1) | US5817811A (en) |
EP (1) | EP0761681B1 (en) |
JP (1) | JP3934708B2 (en) |
AT (1) | ATE214398T1 (en) |
AU (1) | AU708034B2 (en) |
CA (1) | CA2184681C (en) |
DE (2) | DE19532553A1 (en) |
DK (1) | DK0761681T3 (en) |
ES (1) | ES2173230T3 (en) |
NO (1) | NO313833B1 (en) |
PT (1) | PT761681E (en) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6710164B1 (en) | 1993-11-22 | 2004-03-23 | Peter E. Nielsen | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5855911A (en) * | 1995-08-29 | 1999-01-05 | Board Of Regents, The University Of Texas System | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
WO1997023497A1 (en) * | 1995-12-22 | 1997-07-03 | University Technologies International Inc. | Linker arm for solid support oligonucleotide synthesis and process for production thereof |
US6043353A (en) * | 1995-12-22 | 2000-03-28 | University Technologies International, Inc. | Reusable solid support for oligonucleotide synthesis, process for production thereof and process for use thereof |
ATE311402T1 (en) * | 1996-07-24 | 2005-12-15 | Buchardt Dorte | PEPTIDE NUCLEIC ACIDS WITH INCREASED BINDING AFFINITY, SEQUENCE SPECIFICITY AND SOLUBILITY |
US6977244B2 (en) | 1996-10-04 | 2005-12-20 | Board Of Regents, The University Of Texas Systems | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
DE19640974A1 (en) * | 1996-10-04 | 1998-04-16 | Bayer Ag | Building blocks for DNA / PNA cooligomers |
DE59810914D1 (en) * | 1997-05-14 | 2004-04-08 | Morphochem Ag | METHOD FOR PRODUCING POLYMERS HAVING NUCLEO BASES AS SIDE GROUPS |
US7285288B1 (en) | 1997-10-03 | 2007-10-23 | Board Of Regents, The University Of Texas System | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
US7704962B1 (en) | 1997-10-03 | 2010-04-27 | Board Of Regents, The University Of Texas System | Small oligonucleotides with anti-tumor activity |
US7135564B1 (en) * | 1998-07-02 | 2006-11-14 | University Technologies International Inc. | Reusable solid support for oligonucleotide synthesis |
JP2002520008A (en) * | 1998-07-09 | 2002-07-09 | バイオセプト インコーポレイテッド | Use of an improved universal library of peptide nucleic acids to optimize DNA sequence hybridization |
MXPA01010232A (en) * | 1999-04-13 | 2002-03-27 | Basf Ag | Integrin receptor ligands. |
JP4408628B2 (en) * | 2001-03-09 | 2010-02-03 | ボストン プローブス,インコーポレイテッド | Methods, kits, and compositions suitable for combinatorial oligomers and libraries for their preparation |
US6541626B2 (en) * | 2001-04-17 | 2003-04-01 | Isis Pharmaceuticals, Inc. | Process for selective N-acylation of purine nucleosides |
KR20030084444A (en) * | 2002-04-26 | 2003-11-01 | 주식회사 파나진 | A Novel Monomer For Synthesis of PNA Oligomer And A Process For Producing The Same |
EP1585824A4 (en) | 2002-11-21 | 2008-01-02 | Epict Technologies | Preparation and use of single-stranded transcription substrates for synthesis of transcription products corresponding to target sequences |
KR101354692B1 (en) * | 2010-11-26 | 2014-02-06 | 서울대학교산학협력단 | Oligomer and the synthesis of the oligomer |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4408534A1 (en) * | 1994-03-14 | 1995-09-28 | Hoechst Ag | Substituted N-ethyl-glycine derivatives for the production of PNA and PNA / DNA hybrids |
DE4408528A1 (en) * | 1994-03-14 | 1995-09-28 | Hoechst Ag | Peptide oligonucleotide derivatives, their preparation and use |
DE4421536A1 (en) * | 1994-06-20 | 1995-12-21 | Hoechst Ag | Phenyl-substituted alkenylcarboxylic acid guanidines bearing perfluoroalkyl groups, processes for their preparation, their use as medicaments or diagnostic agents, and medicaments containing them |
WO1996040709A1 (en) * | 1995-06-07 | 1996-12-19 | Perseptive Biosystems, Inc. | Pna-dna chimeras and pna synthons for their preparation |
-
1995
- 1995-09-04 DE DE19532553A patent/DE19532553A1/en not_active Withdrawn
-
1996
- 1996-08-22 DE DE59608867T patent/DE59608867D1/en not_active Expired - Lifetime
- 1996-08-22 ES ES96113530T patent/ES2173230T3/en not_active Expired - Lifetime
- 1996-08-22 AT AT96113530T patent/ATE214398T1/en active
- 1996-08-22 PT PT96113530T patent/PT761681E/en unknown
- 1996-08-22 DK DK96113530T patent/DK0761681T3/en active
- 1996-08-22 EP EP96113530A patent/EP0761681B1/en not_active Expired - Lifetime
- 1996-09-02 AU AU64408/96A patent/AU708034B2/en not_active Ceased
- 1996-09-03 CA CA002184681A patent/CA2184681C/en not_active Expired - Fee Related
- 1996-09-03 US US08/707,149 patent/US5817811A/en not_active Expired - Lifetime
- 1996-09-03 NO NO19963677A patent/NO313833B1/en not_active IP Right Cessation
- 1996-09-03 JP JP23269296A patent/JP3934708B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
NO963677D0 (en) | 1996-09-03 |
DK0761681T3 (en) | 2002-07-08 |
AU708034B2 (en) | 1999-07-29 |
EP0761681A2 (en) | 1997-03-12 |
US5817811A (en) | 1998-10-06 |
ATE214398T1 (en) | 2002-03-15 |
AU6440896A (en) | 1997-03-06 |
EP0761681A3 (en) | 1997-07-09 |
CA2184681C (en) | 2010-01-05 |
NO963677L (en) | 1997-03-05 |
JPH09124572A (en) | 1997-05-13 |
NO313833B1 (en) | 2002-12-09 |
DE19532553A1 (en) | 1997-03-06 |
JP3934708B2 (en) | 2007-06-20 |
DE59608867D1 (en) | 2002-04-18 |
EP0761681B1 (en) | 2002-03-13 |
ES2173230T3 (en) | 2002-10-16 |
PT761681E (en) | 2002-08-30 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20150903 |