Synthesis and cytotoxic evaluation of β-alkyl or β-aryl-δ-methyl-α-methylene-δ-lactones. Comparison with the corresponding γ-lactones

被引：26

作者：

Albrecht, Lukasz ^{[1
]}

Wojciechowski, Jakub ^{[2
]}

Albrecht, Anna ^{[1
]}

Wolf, Wojciech M. ^{[2
]}

Janecka, Anna ^{[3
]}

Studzian, Kazimierz ^{[3
]}

Krajewska, Urszula ^{[4
]}

Rozalski, Marek ^{[4
]}

Janecki, Tomasz ^{[1
]}

Krawczyk, Henryk ^{[1
]}

机构：

[1] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland

[2] Tech Univ Lodz, Inst Gen & Ecol Chem, PL-90924 Lodz, Poland

[3] Med Univ Lodz, Dept Biomol Chem, PL-92215 Lodz, Poland

[4] Med Univ Lodz, Dept Pharmaceut Biochem, PL-90151 Lodz, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 02期

关键词：

alpha-Methylene-gamma-lactones; alpha-Methylene-delta-lactones; Horner-Wadsworth-Emmons reaction; Diastereoselective synthesis; Cytotoxic activity; ENANTIOSELECTIVE SYNTHESIS; SESQUITERPENE LACTONES; BIOLOGICAL EVALUATION; CONVENIENT APPROACH; FACILE ROUTE; ANTIMALARIAL; ARTEMISININ; INHIBITORS; ACID;

D O I：

10.1016/j.ejmech.2009.11.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We present a simple and general strategy for the synthesis of beta,delta-disubstituted-alpha-methylene-delta-lactones starting from easily available tert-butyl 2-(diethoxyphosphoryl)alk-2-enoates. The elaborated synthetic protocol includes pyrrolidine-catalyzed Michael addition of acetone, diastereoselective reduction of the carbonyl group, lactonization and finally the Horner-Wadsworth-Emmons reaction with formaldehyde. All alpha-methylene-delta-lactones were evaluated in vitro against mouse leukemia cell line L-1210 and two human leukemia cell lines HL-60 and NALM-6. Comparison of cytotoxic activity with corresponding alpha-methylene-gamma-lactones is also discussed. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：710 / 718

页数：9

共 56 条

[1] Synthesis and cytotoxic activity of γ-aryl substituted α-alkylidene-γ-lactones and α-alkylidene-γ-lactams [J].

Albrecht, Anna ;

Koszuk, Jacek F. ;

Modranka, Jakub ;

Rozalski, Marek ;

Krajewska, Urszula ;

Janecka, Anna ;

Studzian, Kazimierz ;

Janecki, Tomasz .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (09) :4872-4882

[2] Enantioselective Organocatalytic Approach to α-Methylene-δ-lactones and δ-Lactams [J].

Albrecht, Lukasz ;

Richter, Bo ;

Krawczyk, Henryk ;

Jorgensen, Karl Anker .

JOURNAL OF ORGANIC CHEMISTRY, 2008, 73 (21) :8337-8343

[3] Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates [J].

Avery, MA ;

Alvim-Gaston, M ;

Vroman, JA ;

Wu, B ;

Ager, A ;

Peters, W ;

Robinson, BL ;

Charman, W .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (19) :4321-4335

[4] Design, synthesis, and biological evaluation of hybrid molecules containing α-methylene-γ-butyrolactones and polypyrrole minor groove binders [J].

Baraldi, PG ;

Nunez, MD ;

Tabrizi, MA ;

De Clercq, E ;

Balzarini, J ;

Bermejo, J ;

Estévez, F ;

Romagnoli, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (11) :2877-2886

[5] CONFORMATION OF 6-MEMBERED RINGS [J].

BOEYENS, JCA .

JOURNAL OF CRYSTAL AND MOLECULAR STRUCTURE, 1978, 8 (06) :317-320

[6]

*BRUK AXS, 2003, BRUK SADABS BRUK NON

[7]

*BRUK AXS, 2006, BRUK APEX2 VERS 2 1

[8]

*BRUK AXS, 2006, BRUK SAINT PLUS VERS

[9] ISOLATION AND STRUCTURAL ELUCIDATION OF PENTALENOLACTONE-E [J].

CANE, DE ;

ROSSI, T .

TETRAHEDRON LETTERS, 1979, (32) :2973-2974

[10]

CARMICHAEL J, 1987, CANCER RES, V47, P936

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