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Titolo:
Three routes for the synthesis of 6-benzyl-1-ethoxymethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde
Autore:
Petersen, L; Pedersen, EB; Nielsen, C;
Indirizzi:
Odense Univ, Univ So Denmark, Dept Chem, DK-5230 Odense M, Denmark Odense Univ Odense Denmark M nmark, Dept Chem, DK-5230 Odense M, Denmark Statens Serum Inst, Dept Virol, Retrovirus Lab, DK-2300 Copenhagen, Denmark Statens Serum Inst Copenhagen Denmark DK-2300 K-2300 Copenhagen, Denmark
Titolo Testata:
SYNTHESIS-STUTTGART
fascicolo: 4, , anno: 2001,
pagine: 559 - 564
SICI:
0039-7881(200104):4<559:TRFTSO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
INHIBITORS; ASSAY;
Keywords:
HIV-1; non-nucleoside reverse transcriptase inhibitors; MKC-442 analogs; uracil-5-carbaldehydes; 5-vinyluracils;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Pedersen, EB Odense Univ, Univ So Denmark, Dept Chem, Campusvej 55, DK-5230 Odense M, Denmark Odense Univ Campusvej 55 Odense Denmark M Odense M, Denmark
Citazione:
L. Petersen et al., "Three routes for the synthesis of 6-benzyl-1-ethoxymethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde", SYNTHESIS-S, (4), 2001, pp. 559-564

Abstract

6-Benzyl-1-ethoxymethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde (1) is an analog of MKC-442, a very potent inhibitor of HIV-1 reverse transcriptase. Compound 1 was synthesized by three different routes. 6-Benzyl-1-ethoxymethyl-5-vinyl-1H-pyrimidine-2,4-dione (7) was synthesized in five steps from 6-benzyl-1H-pyrimidine-2,4-dione (2) by iodination; N-1 alkylation, N-3 protection, Pd(0) catalyzed coupling with tetravinyltin and then N-3 deprotection. Compound 7 was then cleaved with ozone to give compound 1. In another route compound 2 was hydroxymethylated, oxidized and N-1 alkylated to give compound 1. Finally, compound 1 was synthesized from 6-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (10) by reduction with Raney Nickel followed by N-1 alkylation. An attempt was made to use compound 7 as a precursor for 6-benzyl-1-ethoxymethyl-5-oxiranyl-1H-pyrimidine-2,4-dione (11) by reacting 7 with MCPRA, but compound 11 was too reactive and was ring-opened by the m-chlorobenzoate present in the solution. Two intermediates were N-1 alkylated to give new MKC-442 analogs containing a hydroxymethyl group (13) or a cyano group (14) in the C-5 position. None of the compounds showed activity against the mutated HIV-1 virus (Tyr181Cys) but good activities were observed against wildtype HIV-1 for the intermediates 4and 7 containing iodine or a vinyl group in the C-5 position, respectively.

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Documento generato il 08/04/20 alle ore 11:39:51