Bioaktywne N-acyloamidofosforanowe pochodne nukleozydów

• Autorzy: Kulik K.

Warianty tytułu

EN

Bioactive N-acylphosphoramidate nucleoside derivatives

• Języki publikacji: PL

Abstrakty

EN

Natural nucleotide antibiotics such as Agrocin 84, Dinoguellin, Microcin C and Phosmidosine have a N-acylphosphoramidate linkage at the 5’-hydroxyl of the adenosine derivatives (Fig. 1, 2) [1–3]. They exhibit interesting antifungal, antiemetics and anticancer properties. To synthesize these products, the construction of the N-acylphosphoramidate linkages seems to be a key step. Many groups have described the preparation of such a type of analogues but none of those methods was general. Grandas has for the first time reported the synthesis, of N-acylphosphoramidate peptide-oligonucleotide hybrids via condensation of N-phosphitylated carboxyamides with alcohols in the presence of 1H-tetrazole [9]. Based on this strategy Sekine synthesized aminoacyl adenylate (aa-AMP) analogues which could be useful in the studies on the recognition mechanism of the aminoacylation of tRNA and other biochemical reactions [10]. Since aa-AMPs are extremely unstable under aqueous conditions more stable analogues were required. Aminoacyl-adenylate analogues having an N-acylphosphoramidate linkage (aa-AMPN) could behave as potent, selective asparagine synthetase (AS) inhibitors because of its structural similarity to β-aspartyl-AMP (β AspAMP) which is natural product of AS [17]. Among natural N-acylphosphormiadates, Phosmidosine which connects a nucleoside analogue, 8-oxoadenosine, with an L-proline residue is unique because of its significant antitumor activities and property of stopping cell growth at the G1 phase in the cell cycle (Fig. 2) [2, 13]. The main difficulty during the synthesis of this compound is an extreme instability under weak basic conditions which excludes the use of labile protecting group of basic properties [14]. Stability studies have shown that under basic conditions phosphoryl group of Phosmidosine underwent rapid N–N migration (Scheme 9) [16]. Many modifications have been introduced to improve Phosmidosine properties [16]. Analogues such as demethylated species (Phosmidosine B) have proven to be stable under both basic and acid conditions and are also potential candidates for antitumor drugs [14].

Słowa kluczowe

PL

ugrupowanie N-acyloamidofosforanowe; analogi aminoacyloadenylanów; analogi nukleozydów; Fosmidozyna

EN

N-acylphosphoramidate function; aminoacyl adenylate analogues; nucleoside analogues; Phosmidosine

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Wiadomości Chemiczne
• Rocznik: 2013
• Tom: [Z] 67, 9-10
• Strony: 877--897
• Opis fizyczny: Bibliogr. 19 poz., schem.

Twórcy

autor

Kulik K.

• Centrum Badań Molekularnych i Makromolekularnych w Łodzi Polska Akademia Nauk ul. Sienkiewicza 112, 90-262 Łódź, Poland

Bibliografia

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