Stereoselective synthesis of photoreactive peptidomimetic γ-secretase inhibitors

被引：38

作者：

Chun, J ^{[1
]}

Yin, YI ^{[1
]}

Yang, GL ^{[1
]}

Tarassishin, L ^{[1
]}

Li, YM ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10021 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2004年 / 69卷 / 21期

关键词：

D O I：

10.1021/jo0486948

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The first asymmetric synthesis of novel, potent photoreactive gamma-secretase inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing gamma-secretase activity in the plasma membrane of intact cells.

引用

页码：7344 / 7347

页数：4

共 31 条

[1] TOTAL SYNTHESIS OF BREFELDIN-A [J].

BARTLETT, PA ;

GREEN, FR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1978, 100 (15) :4858-4865

[2] SYNTHESIS OF BETA-ACYLACRYLIC ESTERS AND ALPHA,BETA-BUTENOLIDES VIA BETA-KETO SULFOXIDE ALKYLATION [J].

BARTLETT, PA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1976, 98 (11) :3305-3312

[3] Regulated intramembrane proteolysis: A control mechanism conserved from bacteria to humans [J].

Brown, MS ;

Ye, J ;

Rawson, RB ;

Goldstein, JL .

CELL, 2000, 100 (04) :391-398

[4] New application of the Julia olefination for the synthesis of Tyr-Gly E-alkene and carba isostere pseudopeptides [J].

Charrier, C ;

Ettouati, L ;

Paris, J .

TETRAHEDRON LETTERS, 1999, 40 (31) :5705-5707

[5] A practical method for the preparation of alpha'-chloroketones of N-carbamate protected-alpha-aminoacids [J].

Chen, P ;

Cheng, PTW ;

Spergel, SH ;

Zahler, R ;

Wang, XB ;

Thottathil, J ;

Barrish, JC ;

Polniaszek, RP .

TETRAHEDRON LETTERS, 1997, 38 (18) :3175-3178

[6] Synthesis of new trans double-bond sphingolipid analogues:: Δ4,6,6 and Δ6 ceramides [J].

Chun, J ;

Li, GQ ;

Byun, HS ;

Bittman, R .

JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (08) :2600-2605

[7] METHYLSULFINYL CARBANION (CH3-SO-CH2-) . FORMATION AND APPLICATIONS TO ORGANIC SYNTHESIS [J].

COREY, EJ ;

CHAYKOVSKY, M .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1965, 87 (06) :1345-+

[8] BENZOPHENONE PHOTOPHORES IN BIOCHEMISTRY [J].

DORMAN, G ;

PRESTWICH, GD .

BIOCHEMISTRY, 1994, 33 (19) :5661-5673

[9] Biomedicine - A portrait of Alzheimer secretases - New features and familiar faces [J].

Esler, WP ;

Wolfe, MS .

SCIENCE, 2001, 293 (5534) :1449-1454

[10] A STEREOCONTROLLED SYNTHESIS OF HYDROXYETHYLENE DIPEPTIDE ISOSTERES USING NOVEL, CHIRAL AMINOALKYL EPOXIDES AND GAMMA-(AMINOALKYL) GAMMA-LACTONES [J].

EVANS, BE ;

RITTLE, KE ;

HOMNICK, CF ;

SPRINGER, JP ;

HIRSHFIELD, J ;

VEBER, DF .

JOURNAL OF ORGANIC CHEMISTRY, 1985, 50 (23) :4615-4625

← 1 2 3 4 →