Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides

被引:70
作者
Xu, Dongmin [1 ]
Rivas-Bascon, Nazaret [1 ]
Padial, Natalia M. [1 ]
Knouse, Kyle W. [1 ]
Zheng, Bin [2 ]
Vantourout, Julien C. [1 ]
Schmidt, Michael A. [2 ]
Eastgate, Martin D. [2 ]
Baran, Phil S. [1 ]
机构
[1] Scripps Res, Dept Chem, La Jolla, CA 92037 USA
[2] Bristol Myers Squibb, Chem Dev, New Brunswick, NJ 08903 USA
关键词
EFFICIENT ASYMMETRIC-SYNTHESIS; STEREOSPECIFIC DEOXYGENATION; LIGANDS; OXIDES; STEREOCHEMISTRY; HYDROGENATION; CATALYSIS;
D O I
10.1021/jacs.9b13898
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Phosphorus Incorporation (PI, abbreviated Pi) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from translimonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Pi, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both. enantiomers are available, only one isomer is required.the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.
引用
收藏
页码:5785 / 5792
页数:8
相关论文
共 39 条
[1]   OLIGODEOXYNUCLEOSIDE METHYLPHOSPHONATES - SYNTHESIS AND ENZYMATIC DEGRADATION [J].
AGRAWAL, S ;
GOODCHILD, J .
TETRAHEDRON LETTERS, 1987, 28 (31) :3539-3542
[2]   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
[3]   Enantioselective synthesis of (-)-terpestacin and structural revision of siccanol using catalytic stereoselective fragment couplings and macrocyclizations [J].
Chan, J ;
Jamison, TF .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (34) :10682-10691
[4]   P-chiral, monodentate ferrocenyl phosphines, novel ligands for asymmetric catalysis [J].
Colby, EA ;
Jamison, TF .
JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (01) :156-166
[5]   A NEW AND HIGHLY ENANTIOSELECTIVE SYNTHETIC ROUTE TO P-CHIRAL PHOSPHINES AND DIPHOSPHINES [J].
COREY, EJ ;
CHEN, ZL ;
TANOURY, GJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (23) :11000-11001
[6]  
Engels J., 1982, ANGEW CHEM INT ED EN, V21, P2010
[7]   Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of β-Acetylamino Vinylsulfides: An Approach to Chiral β-Acetylamino Sulfides [J].
Gao, Wenchao ;
Lv, Hui ;
Zhang, Xumu .
ORGANIC LETTERS, 2017, 19 (11) :2877-2880
[8]   Interactions of hairpin oligo-2′-O-methylribonucleotides containing methylphosphonate linkages with HIV TAR RNA [J].
Hamma, T ;
Miller, PS .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2003, 13 (01) :19-30
[9]   Efficient Asymmetric Synthesis of P-Chiral Phosphine Oxides via Properly Designed and Activated Benzoxazaphosphinine-2-oxide Agents [J].
Han, Zhengxu S. ;
Goyal, Navneet ;
Herbage, Melissa A. ;
Sieber, Joshua D. ;
Qu, Bo ;
Xu, Yibo ;
Li, Zhibin ;
Reeves, Jonathan T. ;
Desrosiers, Jean-Nicolas ;
Ma, Shengli ;
Grinberg, Nelu ;
Lee, Heewon ;
Mangunuru, Hari P. R. ;
Zhang, Yongda ;
Krishnamurthy, Dhileep ;
Lu, Bruce Z. ;
Song, Jinhua J. ;
Wang, Guijun ;
Senanayake, Chris H. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (07) :2474-2477
[10]   CHIRAL SYNTHESIS OF Z-2-BUTYLIDENECYCLOHEXAN-1-OL AND Z-2-BUTYLIDENECYCLOHEXAN-1-YL PHENYLSULFIDE FROM OPTICALLY-ACTIVE PHOSPHINE OXIDES [J].
HARMAT, NJS ;
WARREN, S .
TETRAHEDRON LETTERS, 1990, 31 (19) :2743-2746