tailieunhanh - Synthesis of acyclovir as an antiherpes-virus drug

The obtained acyclovir meets the standards in the British Pharmacopoeia 2007 (BP2007). Its activity as inhibitor of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was evaluated according to the plaque reduction assay method and compared with the standard compound. The synthesized acyclovir showed a similar activity as the control. | Journal of Chemistry, Vol. 47 (4), P. 523 - 528, 2009 SYNTHESIS OF ACYCLOVIR AS AN ANTIHERPES-VIRUS DRUG Received 4 February 2009 1 Tran Quang Hung , Nguyen Thi Thuong2, Tran Van Sung1 1 Laboratory of Organic Synthesis, Institute of Chemistry, VAST 2 Laboratory of Herpes viruses, Faculty of Virus, National Institute of Hygiene and Epidemiology Abstract A one-pot process for high-yield regioselective synthesis of 9-[(2-hydroxyethoxy) methyl]guanine (acyclovir), an antiherpetic agent, was achieved from guanine via the steps of reacting of N2,N9 -diprotected guanine with 1-acetyl-2-acetylmethoxy-ethyleneglycol in presence of phosphoric acid or polyphosphoric acid. Total yield of product was 59%. The obtained acyclovir meets the standards in the British Pharmacopoeia 2007 (BP2007). Its activity as inhibitor of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was evaluated according to the plaque reduction assay method and compared with the standard compound. The synthesized acyclovir showed a similar activity as the control. Keywords: Acyclovir, Herpes simplex virus, Nucleoside, One- pot synthesis. I - Introduction Virus was a cause of many dangerous diseases and variety of epidemic diseases in large area. It is important that antibiotics have no or almost no effect on viruses. Although the production of herpes vaccine is desired by many countries but it still stays on a testing level. The prevention of herpes infection is a special problem because the disease often recurred in present of antibody. Therefore, development of anti-virus drugs is important, necessary and still be a leading interest. 1: Acyclovir Acyclovir, {9-[(2-hydroxyethoxy)methyl] guanine} (ACV 1), was first reported by Schaeffer and co-workers [1] and is a nucleoside analogue. It acts selectively on herpes-infected cells. It has specific inhibition effects on replication of herpes virus simplex type 1 and type 2 (HSV1 and HSV2) and Varicella zoster virus that cause almost no intoxication