Therapeutic Application and Preparation of Posaconazole
As of May 24th, the number of Covid-19 cases in India has reached 26.75 million – second only to the US. Meanwhile, India has reported nearly 9,000 cases of the "black fungus" threatening COVID-19 patients and survivors. The violent and sweeping black fungus complicates India’s fight against the pandemic.
Research Background
Black fungus, also known as mucormycosis, is a rare but dangerous infection. It is caused by mucormycetes and often affects the rhino-orbito-cerebral, pulmonary, and chest after inhalation. If worse, it may cause damage to the upper jaw and even blindness [1].
Liposomal amphotericin B, as a polyene drug, is the first choice when comes to mucormycosis anti-fungal agents. However, the significant side effects make new therapeutic methods urgent [1].
Posaconazole, a triazole anti-fungal drug, was approved by the FDA for prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections and oropharyngeal candidiasis (OPC), and the treatment of invasive fungal infections resistant to other antifungal drugs [2].
References
[1] Lin E, et al. Pulmonary mucormycosis: clinical features and outcomes. Infection. 2017, 45(4): 443-448.
[2] Clark NM, et al. Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections. Semin Respir Crit Care Med. 2015, 36(5): 767-785.
[3] A process for the manufacture of Posaconazole. WO 2019/077627 Al.
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Preparation and Synthesis[3]
The synthetic route of Posaconazole
Scheme A:
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