A new approach to the synthesis of Anti-Reverse Cap Analog (ARCA) 2mGpppG

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Resumo

A new approach to the synthesis of Anti-Reverse Cap Analog (ARCA) of the classical structure – dimethylated guanosine dinucleotide 2mGpppG is proposed. The classical approach to obtaining consists in condensation of activated 5′-diphosphate of 7,3′-O-dimethylguanosine with 5′-guanosine monophosphate. We suggest to use a commercially available 3′-O-methylguanosine for the synthesis of 5′-monophosphate of dimethylated guanosine only, and to use an activated 5′-guanosine diphosphate in the condensation. The conditions of 3′-O-methylguanosine phosphorylation were determined to avoid the formation of a side product 3′-O-methyl-5′-deoxy-5′-chloroguanosine-3′-phosphate. ARCA was synthesized with a high yield (89% at the condensation stage). Our approach to the synthesis is easily scaled and can be used for a preparative synthesis of ARCA (several grams).

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Sobre autores

A. Kayushin

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Autor responsável pela correspondência
Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

K. Antonov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

E. Dorofeeva

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

M. Berzina

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

A. Arnautova

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

I. Prohorenko

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

A. Miroshnikov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

I. Konstantinova

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: kayushin.alexej@yandex.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997

Bibliografia

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2. Fig. 1. Condensation sites during the production of ARCA (I): (a) – classic version [5] (red line); (b) – proposed by us (green line).

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3. Fig. 2. Synthesis scheme for ARCA (I).

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4. Fig. 3. Structure of by-product (VII) in the synthesis of 7,3′-O-dimethylguanosine 5′-monophosphate (V).

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