Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis

被引:25
作者
Andresen, TL [1 ]
Skytte, DM [1 ]
Madsen, R [1 ]
机构
[1] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark
关键词
D O I
10.1039/b411021h
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A divergent strategy is described for synthesis of the novel phosphatidylinositols 1-3. The synthetic approach commences from benzyl-protected methyl 6-iodo-6-deoxy-alpha-D-glucopyranoside, which undergoes zinc-mediated reductive fragmentation followed by vinyl Grignard addition and ring-closing metathesis to afford the key conduritol B intermediate 7. This can trifurcate to form three different benzyl-protected myo-inositol headgroups 4-6, which after phosphorylation and attachment of the glycerolipid part give phosphatidylinositols 1-3. Preliminary biological testing against human colon adenocarcinoma cells reveals that analogues 1-3 are significant anti-tumour agents.
引用
收藏
页码:2951 / 2957
页数:7
相关论文
共 61 条
[51]   Zinc-mediated fragmentation of methyl 6-deoxy-6-iodo-hexopyranosides [J].
Skaanderup, PR ;
Hyldtoft, L ;
Madsen, R .
MONATSHEFTE FUR CHEMIE, 2002, 133 (04) :467-472
[52]  
Skaanderup PR, 2002, SYNTHESIS-STUTTGART, P1721
[53]   A simple and practical resolution of 1,2:4,5-di-O-isopropylidene-myo-inositol [J].
Sureshan, KM ;
Yamasaki, T ;
Hayashi, M ;
Watanabe, Y .
TETRAHEDRON-ASYMMETRY, 2003, 14 (13) :1771-1774
[54]   Novel synthesis of enantiomerically pure natural inositols and their diastereoisomers [J].
Takahashi, H ;
Kittaka, H ;
Ikegami, S .
JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (08) :2705-2716
[55]   IMPROVED PREPARATION OF 1,6-ANHYDRO-4-DEOXY-2-O-P-TOLUENESULFONYL-BETA-D-XYLO-HEXOPYRANOSE AND OF ITS D-[4-H-2]GLUCO-ANALOG FROM 1,6/3,4-DIANHYDRO-2-O-P-TOLUENESULFONYL-BETA-D-GALACTOPYRANOSE [J].
TRNKA, T ;
BUDESINSKY, M ;
CERNY, M .
CARBOHYDRATE RESEARCH, 1994, 259 (01) :131-134
[56]   The development of L2X2Ru=CHR olefin metathesis catalysts:: An organometallic success story [J].
Trnka, TM ;
Grubbs, RH .
ACCOUNTS OF CHEMICAL RESEARCH, 2001, 34 (01) :18-29
[57]   Dynamic kinetic asymmetric transformations of conduritol B tetracarboxylates:: An asymmetric synthesis of D-myo-inositol 1,4,5-trisphosphate [J].
Trost, BM ;
Patterson, DE ;
Hembre, EJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (46) :10834-10835
[58]  
Trost BM, 2001, CHEM-EUR J, V7, P3768, DOI 10.1002/1521-3765(20010903)7:17<3768::AID-CHEM3768>3.0.CO
[59]  
2-C
[60]   THE TOTAL SYNTHESIS OF MYOINOSITOL POLYPHOSPHATES [J].
VACCA, JP ;
DESOLMS, SJ ;
HUFF, JR ;
BILLINGTON, DC ;
BAKER, R ;
KULAGOWSKI, JJ ;
MAWER, IM .
TETRAHEDRON, 1989, 45 (17) :5679-5702