Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides

被引：19

作者：

LeeRuff, E ^{[1
]}

Ostrowski, M ^{[1
]}

Ladha, A ^{[1
]}

Stynes, DV ^{[1
]}

Vernik, I ^{[1
]}

Jiang, JL ^{[1
]}

Wan, WQ ^{[1
]}

Ding, SF ^{[1
]}

Joshi, S ^{[1
]}

机构：

[1] UNIV TORONTO,DEPT MICROBIOL,TORONTO,ON M5S 1A8,CANADA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 26期

关键词：

D O I：

10.1021/jm950822k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared based on the photo chemical ring expansion of a chiral cyclobutanone precursor, (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a B-substituted purine. Both alpha- and beta-anomers are produced in this transformation. Deprotection was effected by reaction of the photoadducts with saturated methanolic ammonia. Nine purine nucleosides were tested for their inhibitory effect of HIV IIIB virus on H9 cells. The 6-hexyloxy and adenine derivatives 4e,c, respectively, appeared to be most effective at inhibiting viral reproduction with 4e comparable in activity to ddI and AZT.

引用

收藏

页码：5276 / 5280

页数：5

相关论文

共 17 条

[1] AN EFFICIENT AND DIASTEREOSELECTIVE [2+2] CYCLOADDITION - CONVENIENT AND ENANTIOSELECTIVE ROUTE TO TRANS-2',3'-DIHYDROXYMETHYLCYCLOBUTANE NUCLEOSIDE ANALOGS [J].

AHMAD, S .

TETRAHEDRON LETTERS, 1991, 32 (48) :6997-7000

[2]

AHMAD S, 1991, Patent No. 458643

[3] NOVEL 6-ALKOXYPURINE 2',3'-DIDEOXYNUCLEOSIDES AS INHIBITORS OF THE CYTOPATHIC EFFECT OF THE HUMAN-IMMUNODEFICIENCY-VIRUS [J].

BURNS, CL ;

STCLAIR, MH ;

FRICK, LW ;

SPECTOR, T ;

AVERETT, DR ;

ENGLISH, ML ;

HOLMES, TJ ;

KRENITSKY, TA ;

KOSZALKA, GW .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (03) :378-384

[4] THE EFFICACY OF AZIDOTHYMIDINE (AZT) IN THE TREATMENT OF PATIENTS WITH AIDS AND AIDS-RELATED COMPLEX - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].

FISCHL, MA ;

RICHMAN, DD ;

GRIECO, MH ;

GOTTLIEB, MS ;

VOLBERDING, PA ;

LASKIN, OL ;

LEEDOM, JM ;

GROOPMAN, JE ;

MILDVAN, D ;

SCHOOLEY, RT ;

JACKSON, GG ;

DURACK, DT ;

KING, D .

NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (04) :185-191

[5] A NOVEL-APPROACH TOWARDS 2,3-DIDEOXYRIBOSIDE SYNTHESIS [J].

LEERUFF, E ;

JIANG, JL ;

WAN, WQ .

TETRAHEDRON LETTERS, 1993, 34 (02) :261-264

[6] Enantioselective preparation of 2',3'-dideoxynucleosides and their analogues from ring-expansion of cyclobutanones .2. Synthesis of 2',3'-dideoxyribosides and (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane [J].

LeeRuff, E ;

Xi, FD ;

Qie, JH .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (04) :1547-1550

[7] A NOVEL-APPROACH TOWARD THE SYNTHESIS OF CHIRAL 2,3-DIDEOXY NUCLEOSIDES AND THEIR CARBOCYCLIC ANALOGS [J].

LEERUFF, E ;

WAN, WQ ;

JIANG, JL .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (08) :2114-2118

[8] SELECTIVE-INHIBITION OF HUMAN CYTOMEGALO-VIRUS REPLICATION BY A NOVEL NUCLEOSIDE, OXETANOCIN-G [J].

NISHIYAMA, Y ;

YAMAMOTO, N ;

TAKAHASH, K ;

SHIMADA, N .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1988, 32 (07) :1053-1056

[9] LYMPHOCYTES FROM HIV-INFECTED INDIVIDUALS SHOW ABERRANT INOSITOL POLYPHOSPHATE METABOLISM WHICH REVERSES AFTER ZIDOVUDINE THERAPY [J].

NYE, KE ;

KNOX, KA ;

PINCHING, AJ .

AIDS, 1991, 5 (04) :413-417

[10] SYNTHESIS OF THE DIDEOXYNUCLEOSIDES DDC AND CNT FROM GLUTAMIC-ACID, RIBONOLACTONE, AND PYRIMIDINE-BASES [J].

OKABE, M ;

SUN, RC ;

TAM, SYK ;

TODARO, LJ ;

COFFEN, DL .

JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (20) :4780-4786