Unlocking P(V): Reagents for chiral phosphorothioate synthesis

被引：197

作者：

Knouse, Kyle W. ^{[1
]}

deGruyter, Justine N. ^{[1
]}

Schmidt, Michael A. ^{[2
]}

Zheng, Bin ^{[2
]}

Vantourout, Julien C. ^{[1
]}

Kingston, Cian ^{[1
]}

Mercer, Stephen E. ^{[3
]}

Mcdonald, Ivar M. ^{[3
]}

Olson, Richard E. ^{[3
]}

Zhu, Ye ^{[2
]}

Hang, Chao ^{[2
]}

Zhu, Jason ^{[2
]}

Yuan, Changxia ^{[2
]}

Wang, Qinggang ^{[2
]}

Park, Peter ^{[4
]}

Eastgate, Martin D. ^{[2
]}

Baran, Phil S. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[2] Bristol Myers Squibb Co, Chem & Synthet Dev, One Squibb Dr, New Brunswick, NJ 08903 USA

[3] Bristol Myers Squibb Co, Dept Discovery Chem, Res & Dev, 5 Res Pkwy, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Co, Dept Discovery Chem, POB 5400, Princeton, NJ 08543 USA

来源：

SCIENCE | 2018年 / 361卷 / 6408期

关键词：

SOLID-PHASE SYNTHESIS; C-DI-GMP; STEREOCONTROLLED SYNTHESIS; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; GUANYL OLIGONUCLEOTIDE; THIOPHOSPHATE ANALOGS; DIGUANYLIC ACID; MONOMERS;

D O I：

10.1126/science.aau3369

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Phosphorothioate nucleotides have emerged as powerful pharmacological substitutes of their native phosphodiester analogs with important translational applications in antisense oligonucleotide (ASO) therapeutics and cyclic dinucleotide (CDN) synthesis. Stereocontrolled installation of this chiral motif has long been hampered by the systemic use of phosphorus(III) [P(III)]-based reagent systems as the sole practical means of oligonucleotide assembly. A fundamentally different approach is described herein: the invention of a P(V)-based reagent platform for programmable, traceless, diastereoselective phosphorus-sulfur incorporation. The power of this reagent system is demonstrated through the robust and stereocontrolled synthesis of various nucleotidic architectures, including ASOs and CDNs, via an efficient, inexpensive, and operationally simple protocol.

引用

页码：1234 / 1238

页数：5

共 40 条

[1] STEREOSELECTIVE SYNTHESIS OF CYCLIC DINUCLEOTIDE PHOSPHOROTHIOATES [J].

BATTISTINI, C ;

FUSTINONI, S ;

BRASCA, MG ;

BORGHI, D .

TETRAHEDRON, 1993, 49 (05) :1115-1132

[2] DEOXYNUCLEOSIDE PHOSPHORAMIDITES - A NEW CLASS OF KEY INTERMEDIATES FOR DEOXYPOLYNUCLEOTIDE SYNTHESIS [J].

BEAUCAGE, SL ;

CARUTHERS, MH .

TETRAHEDRON LETTERS, 1981, 22 (20) :1859-1862

[3] Electronic Structures of LNA Phosphorothioate Oligonucleotides [J].

Bohr, Henrik G. ;

Shim, Irene ;

Stein, Cy ;

Orum, Henrik ;

Hansen, Henrik F. ;

Koch, Troels .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2017, 8 :428-441

[4] STING is a direct innate immune sensor of cyclic di-GMP [J].

Burdette, Dara L. ;

Monroe, Kathryn M. ;

Sotelo-Troha, Katia ;

Iwig, Jeff S. ;

Eckert, Barbara ;

Hyodo, Mamoru ;

Hayakawa, Yoshihiro ;

Vance, Russell E. .

NATURE, 2011, 478 (7370) :515-U111

[5]

Caruthers M.H., 1987, Synthesis and Applications of DNA and RNA, P47

[6] (3′-5′)-Cyclic Dinucleotides: Synthetic Strategies and Biological Potential [J].

Clivio, Pascale ;

Coantic-Castex, Stephanie ;

Guillaume, Dominique .

CHEMICAL REVIEWS, 2013, 113 (10) :7354-7401

[7]

Cooke S.T., 1998, Antisense research and applications, V1st

[8]

Cross R., 2018, CHEM ENG NEWS, V96, P24

[9] Gene therapy comes of age [J].

Dunbar, Cynthia E. ;

High, Katherine A. ;

Joung, J. Keith ;

Kohn, Donald B. ;

Ozawa, Keiya ;

Sadelain, Michel .

SCIENCE, 2018, 359 (6372) :175-+

[10] Catalytic carbene transfer allows the direct customization of cyclic purine dinucleotides [J].

Fei, Na ;

Haeussinger, Daniel ;

Bluemli, Seraina ;

Laventie, Benoit-Joseph ;

Bizzini, Lorenzo D. ;

Zimmermann, Kaspar ;

Jenal, Urs ;

Gillingham, Dennis .

CHEMICAL COMMUNICATIONS, 2014, 50 (62) :8499-8502

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