5-fluorouracil derivatives .1. Acyclonucleosides through a tin(IV) chloride-mediated regiospecific ring opening of alkoxy-1,4-diheteroepanes

被引：24

作者：

Campos, J ^{[1
]}

Pineda, MJ ^{[1
]}

Gomez, JA ^{[1
]}

Entrena, A ^{[1
]}

Trujillo, MA ^{[1
]}

Gallo, MA ^{[1
]}

Espinosa, A ^{[1
]}

机构：

[1] FAC FARM, DEPT QUIM ORGAN, E-18071 GRANADA, SPAIN

来源：

TETRAHEDRON | 1996年 / 52卷 / 26期

关键词：

D O I：

10.1016/0040-4020(96)00439-5

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The reaction of 5-fluorouracil with the seven-membered acetals la-g in the presence of tin (IV) chloride, trimethylchlorosilane and hexamethuldisilazane at room temperature gives 1-{[3-(2-hydroxyethylhetero)-1-alkoxy]alkyl}-5-fluorouracils 2a-f and 1-{[2-(3-hydroxypropoxy)-1-isopropoxy]ethyl}-5-fluorouracil 2g in 31-86 % yields. The presence of an heteroatom on the 1-position of the cycloacetal and the use of tin (IV) chloride, capable of a 1, 4-chelation, seem to impose their influence in the regiospecific ring opening of 1a-g. The conformational analyses carried out on 26 and (1R.3R)-2e and (1R,3S)-2e clearly indicate that the N-1(sp(2))-C-1 -C-2 -C-3 moiety tends to fold in a gauche conformation. The antitumour activities of compounds 2b-g were assessed against HEp human cells showing that 2c is 4-fold more active than 5-FU. The drugs studied do not show am clear toxicity in comparison with the toxic effect of 5-FU. (C) 1996 Elsevier Science Ltd

引用

页码：8907 / 8924

页数：18

共 43 条

[1] SYNTHESIS AND INTERACTION WITH URIDINE PHOSPHORYLASE OF 5'-DEOXY-4',5-DIFLUOROURIDINE, A NEW PRODRUG OF 5-FLUOROURACIL [J].