A practical entry to β-aryl-β-alkyl amino alcohols: application to the synthesis of a potent BACE1 inhibitor

被引：13

作者：

Delgado, Oscar ^{[1
]}

Monteagudo, Antonio ^{[2
]}

Van Gool, Michiel ^{[1
]}

Trabanco, Andres A. ^{[1
]}

Fustero, Santos ^{[2
,3
]}

机构：

[1] Janssen Res & Dev, Neurosci Med Chem Dept, E-45007 Toledo, Spain

[2] Ctr Invest Principe Felipe, Lab Mol Organ, E-46012 Valencia, Spain

[3] Univ Valencia, Dept Quim Organ, E-46100 Burjassot, Spain

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2012年 / 10卷 / 33期

关键词：

ASYMMETRIC-SYNTHESIS; SECRETASE; KETIMINES; ENZYMES; DISEASE; DESIGN; ACIDS;

D O I：

10.1039/c2ob25845e

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The 1,2-addition of alkyl Grignard reagents to readily available N-tert-butanesulfinyl ketimines, bearing an alpha-silyloxy substituent, proceeds in high yields and excellent diastereocontrol. The utility of the present method was demonstrated by the synthesis, in enantiomerically pure form, of one recently disclosed beta-secretase (BACE1) inhibitor.

引用

页码：6758 / 6766

页数：9

共 28 条

[21] Alzheimer's disease: Genes, proteins, and therapy [J].

Selkoe, DJ .

PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :741-766

[22] Asymmetric synthesis of protected 1,2-amino alcohols using tert-butanesulfinyl aldimines and ketimines [J].

Tang, TP ;

Volkman, SK ;

Ellman, JA .

JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (26) :8772-8778

[23]

Trabanco-Suarez A. A., 2011, WO Pat, Patent No. [154 431, 154431]

[24] Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors [J].

Tresadern, Gary ;

Delgado, Francisca ;

Delgado, Oscar ;

Gijsen, Harrie ;

Macdonald, Gregor J. ;

Moechars, Dieder ;

Rombouts, Frederik ;

Alexander, Richard ;

Spurlino, John ;

Van Gool, Michiel ;

Antonio Vega, Juan ;

Trabanco, Andres A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (24) :7255-7260

[25] β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE [J].

Vassar, R ;

Bennett, BD ;

Babu-Khan, S ;

Kahn, S ;

Mendiaz, EA ;

Denis, P ;

Teplow, DB ;

Ross, S ;

Amarante, P ;

Loeloff, R ;

Luo, Y ;

Fisher, S ;

Fuller, L ;

Edenson, S ;

Lile, J ;

Jarosinski, MA ;

Biere, AL ;

Curran, E ;

Burgess, T ;

Louis, JC ;

Collins, F ;

Treanor, J ;

Rogers, G ;

Citron, M .

SCIENCE, 1999, 286 (5440) :735-741

[26] Aβ-generating enzymes:: Recent advances in β- and γ-secretase research [J].

Vassar, R ;

Citron, M .

NEURON, 2000, 27 (03) :419-422

[27] Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity [J].

Wolfe, MS ;

Xia, WM ;

Ostaszewski, BL ;

Diehl, TS ;

Kimberly, WT ;

Selkoe, DJ .

NATURE, 1999, 398 (6727) :513-517

[28] Design, synthesis, and evaluation of novel ethambutol analogues [J].

Yendapally, Raghunandan ;

Lee, Richard E. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (05) :1607-1611

← 1 2 3 →