1. Expanding horizons of shikimic acid
Recent progresses in production and its endless frontiers in application and market trends
Garima Rawat & Priyanka Tripathi & R. K. Saxena. Appl Microbiol Biotechnol (2013) 97:4277–4287
Shikimic acid also has a plethora of interesting industrial application. As discussed previously, in pharmaceuticals shikimic acid acts as starting material for the synthesis of drug Oseltamivir phosphate (Tamiflu) (Knop et al. 2001; Nie et al. 2009;Pollack 2005; Raghavendra et al. 2009;Knopetal. 2001). Current industrial synthesis of Oseltamivir phosphate (Fig. 5) has been developed by the chemists at Gilead Sciences, Inc. and F. Hoffman-La Roche. Among all the reported syntheticmethods, La Roche’smethod seems to have been the best one for industrial large-scale preparation of Tamiflu, but there are some drawbacks associated with this method like the long synthetic route and the relatively low total yield. In this context, a short and practical synthesis of Oseltamivir Phosphate (Tamiflu) from (−)-Shikimic acid has been reported (Nie et al. 2009) which constitute overall eight steps and high yield (47 %) (Fig. 5). Other merits include inexpensive reagents, mildness of the reaction conditions, and ease of manipulation of every step. Shikimic acid is also considered as a useful additive in hair growth products due to the interaction in the biochemistry of serotonin and melatonin which is recently reported to be involved in treatment of alopecia (Guglielmini 2010; Sakaguchi et al. 2004).
2. Effects of oseltamivir phosphate (Tamiﬂu®) in human sera on results of microneutralization and hemagglutinin-inhibition tests for H5N2 avian inﬂuenza virus
Yoshinao Yamazaki , M. Doy , S. Yamato. Y. Kawada, T. Ogata. Arch Virol (2008) 153:945–949
During this outbreak, many MNT-positive individuals were prescribed oseltamivir phosphate (OP; Tamiﬂu®). OP is an orally active prodrug of oseltamivir carboxylate (OC), which is particularly effective against the inﬂuenza virus neuraminidase; it is designed to target conserved residues at the neuraminidase enzyme active site of inﬂuenza A and B viruses. Koopmans et al. suggested that the prophylactic use of oseltamivir was associated with the development of anti-inﬂuenza A virus antibodies. This may be regarded as a false-positive result caused by the presence of unknown agents. Clariﬁcation of the MNT-positive results in Ibaraki as true positives or false positives is required.
3. High and continuous exposure of laninamivir, an anti-inﬂuenza drug, may work suppressively to generate low-susceptibility mutants in animals
huku Kubo • Akane Tokumitsu • Takanori Tomozawa • Masayo Kakuta • Makoto Yamashita. J Infect Chemother (2012) 18:69–74
Mice anesthetized with 2.5% isoﬂurane were infected intranasally on day 0 with 30 plaque-forming units/mouse of A/PR/8/34. For the laninamivir octanoate group, the anesthetized mice were intranasally administered 50 ll laninamivir octanoate at 80 lg/kg once at 9 h post infection (hpi) after one cycle replication of the infected viruses, then saline was orally administered according to the oseltamivir phosphate administration schedule. For the oseltamivir phosphate group, 200 ll oseltamivir phosphate at 1 mg/kg beginning at 9 hpi was continued twice daily for a total of ten times. For the control group, saline was both intranasally and orally administered at 9 hpi, then orally administered according to the oseltamivir phosphate administration schedule.
4. Simple and Sensitive Spectrofluorimetric Methodmfor the Determination of Oseltamivir Phosphate in Capsules Through Derivatization with Fluorescamine
Zeynep Aydoğmuş. J Fluoresc (2009) 19:673–679
Oseltamivir phosphate (OSP) (3R,4R,5S)-4-acetylamino-5-amino-3(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid ethyl ester, phosphate (Fig. 1) is an antiviral drug used in the treatment and prophylaxis of both influenza virus A and influenza virus B. Oseltamivir phosphate (OSP) is an ethyl ester pro-drug that is rapidly and extensively metabolized by esterases in the gastrointestinal tract and liver to its active form, oseltamivir carboxylate (OSC). There are some analytical methods in the literature for the analysis of Oseltamivir phosphate (OSP) or its active metabolite, OSC in the biological fluids and pharmaceutical preparations. Three high performance liquid chromatography (HPLC) methods with fluorescence in plasma and with UV detection in human serum and in biological materials have been reported for the analysis of OSC. An enzymatic assay based on neuraminidase inhibition has also reported for analysis of OSC . A liquid chromatography/mass spectrometry (LC/MS) with solid phase extraction and LC-tandem MS methods for determination of OSP and OSC in human and animal plasma, urine and saliva have been reported. Three high performance liquid chromatography (HPLC) and colorimetric methods have been reported for determination of OSP in pharmaceutical preparations. These methods offered the required sensitivity for the analysis oseltamivir in pharmaceutical dosage forms and biological fluids; however their sophisticated instrumentation and high-analysis cost limited their use for analysis of oseltamivir (OSP).