Title:
オリゴヌクレオチド合成用新規硫黄転移試薬
Document Type and Number:
Japanese Patent JP4393594
Kind Code:
B2
Abstract:
In our research, two commercially available compounds, 3-amino-1,2,4-dithiazole-5-thione (1) and xanthane hydride (2), and their derivatives 3-6 are found to be potential sulfur-transfer reagents. The efficiency and optimization of these new sulfur-transfer reagents were investigated by solid-phase syntheses of dinudeotide and oligonucleotide phosphorothioates. The results show that both compounds 1 and 2 are highly efficient sulfurizing reagents, and better than 99% sulfur transfer efficiency can be achieved at each step. In contrast to Beaucage reagent, these novel sulfur-transfer reagents are very stable in various solvents, and are available in bulk quantities at low cost. Due to these advantages, compounds 1 and 2 can be considered alternatives to Beaucage reagent, especially in large-scale preparation of oligonucleotide phosphorothioates. Furthermore, compounds 1 and 2 were modified to enhance their solubility in acetonitrile. Three types of structure, as described as Formulae I, II, and III, are considered as potential efficient sulfur-transfer reagents based on our results.
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Inventors:
Han, Young Shin
Tan, jimmy
Jean, Joada
Tan, Jin-Yang
Tan, jimmy
Jean, Joada
Tan, Jin-Yang
Application Number:
JP50080299A
Publication Date:
January 06, 2010
Filing Date:
May 26, 1998
Export Citation:
Assignee:
Avecia Biotechnology Incorporated
International Classes:
C07D285/125; C07D285/00; C07D285/135; C07D285/12; C07D285/16; C07H21/00
Domestic Patent References:
| JP7025864A |
Foreign References:
| US3753908 |
Other References:
XU, Q., et al., Use of 1,2,4-dithiazolidine-3,5-dione(DtsNH) and 3-ethoxy-1,2,4-dithiazoline-5-one(EDITH) for synthesis of phosphorothioate-containing oligodeoxyribonucleotides, Nucleic Acids Research, 1996年, 24(9), p. 1602-1607
XU, Q., et al., Efficient introduction of phosphorothioates into RNA oligonucleotides by 3-ethoxy-1,2,4-dithiazoline-5-one(EDITH), Nucleic Acids Research, 1996年, 24(18), p. 3643-3644
TITTELBACH, F., Synthesis and Dimroth Rearrangement of Disubstituted 5-imino-1,2,4-dithiazolidine-3-thiones, Journal fuer Praktische Chemie. Chemiker-Zeitung, 1991年, 333(1), p. 107-117
TITTELBACH, F., et al., Cycloaddition-Elimination Reactions of Phenyl Isocyanate with Oxo and Thiono Derivatives of Aliphatic Substituted 5-Imino-1,2,4-Dithiazolidines and 3-Thiono-1,2,4-Thiadiazolidines, Journal fuer Praktische Chemie. Chemiker-Zeitung, 1992年, 334(8), p. 685-690
XU, Q., et al., Efficient introduction of phosphorothioates into RNA oligonucleotides by 3-ethoxy-1,2,4-dithiazoline-5-one(EDITH), Nucleic Acids Research, 1996年, 24(18), p. 3643-3644
TITTELBACH, F., Synthesis and Dimroth Rearrangement of Disubstituted 5-imino-1,2,4-dithiazolidine-3-thiones, Journal fuer Praktische Chemie. Chemiker-Zeitung, 1991年, 333(1), p. 107-117
TITTELBACH, F., et al., Cycloaddition-Elimination Reactions of Phenyl Isocyanate with Oxo and Thiono Derivatives of Aliphatic Substituted 5-Imino-1,2,4-Dithiazolidines and 3-Thiono-1,2,4-Thiadiazolidines, Journal fuer Praktische Chemie. Chemiker-Zeitung, 1992年, 334(8), p. 685-690
Attorney, Agent or Firm:
Kazuo Shamoto
Tadashi Masui
Yasushi Kobayashi
Akio Chiba
Hiroyuki Tomita
Tadashi Masui
Yasushi Kobayashi
Akio Chiba
Hiroyuki Tomita