D-ring substituted rhazinilam analogues:: Semisynthesis and evaluation of antitubulin activity

被引：31

作者：

Dupont, C ^{[1
]}

Guénard, D ^{[1
]}

Tchertanov, L ^{[1
]}

Thoret, S ^{[1
]}

Guéritte, F ^{[1
]}

机构：

[1] CNRS, Inst Chim Subst Nat, F-91198 Gif Sur Yvette, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 12期

关键词：

natural products; rhazinilam; tubulin; cytotoxicity; structure-activity relationships;

D O I：

10.1016/S0968-0896(99)00241-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel (-)- and (+)-rhazinilam derivatives substituted on the D-ring (compounds 3, 4, 5 and 6) have been prepared from (+)-vincadifformine 7 and (-)-tabersonine and evaluated against the disassembly of microtubules into tubulin. Along with this study, a reproducible 'one pot' semisynthesis of (-)-rhazinilam 1 from (+)-1,2-didehydroaspidospermidine 2 was performed allowing the easy preparation of these new compounds. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2961 / 2969

页数：9

共 23 条

[1]

ABRAHAM D J, 1972, Tetrahedron Letters, V10, P909

[2] SYNTHESIS OF TRICYCLIC PHENYLPYRROLE LACTAMS, NEW MODELS OF ANTITUBULIN AGENTS [J].

ALAZARD, JP ;

MILLETPAILLUSSON, C ;

BOYE, O ;

GUENARD, D ;

CHIARONI, A ;

RICHE, C ;

THAL, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (12) :725-728

[3]

Alazard JP, 1996, B SOC CHIM FR, V133, P251

[4] APPROACHES TO THE SYNTHESIS OF ASPIDOSPERMA ALKALOIDS .2. THE SYNTHESIS OF 18,19-DIDEHYDROTABERSONINE [J].

BLOWERS, JW ;

SAXTON, JE ;

SWANSON, AG .

TETRAHEDRON, 1986, 42 (21) :6071-6095

[5] TOXICITY DETERMINED INVITRO BY MORPHOLOGICAL ALTERATIONS AND NEUTRAL RED ABSORPTION [J].

BORENFREUND, E ;

PUERNER, JA .

TOXICOLOGY LETTERS, 1985, 24 (2-3) :119-124

[6] SELECTIVE BORANE REDUCTION OF TRIFLUOROACETAMIDE SUBSTITUENT IN PRESENCE OF A CARBAMATE [J].

CURRAN, WV ;

ANGIER, RB .

JOURNAL OF ORGANIC CHEMISTRY, 1966, 31 (11) :3867-&

[7] Hemisynthesis of rhazinilam analogues: Structure-activity relationships on tubulin-microtubule system [J].

David, B ;

Sevenet, T ;

Thoison, O ;

Awang, K ;

Pais, M ;

Wright, M ;

Guenard, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (17) :2155-2158

[8] RHAZINILAM MIMICS THE CELLULAR EFFECTS OF TAXOL BY DIFFERENT MECHANISMS OF ACTION [J].

DAVID, B ;

SEVENET, T ;

MORGAT, M ;

GUENARD, D ;

MOISAND, A ;

TOLLON, Y ;

THOISON, O ;

WRIGHT, M .

CELL MOTILITY AND THE CYTOSKELETON, 1994, 28 (04) :317-326

[9]

DAVID B, 1990, THESIS U R DESCARTES

[10]

DESILVA KT, 1972, TETRAHEDRON LETT, V10, P913

← 1 2 3 →