Amalgamation of Synthetic Biology and Chemistry for High-Throughput Nonconventional Synthesis of the Antimalarial Drug Artemisinin
| Autor: | Ganesh Devidas Mahale, Subhash Singh, Brajesh Sharma, Neeraj Kumar, Ashok Kumar, Yogesh Patel, Christopher J. Paddon, Dharmendra Singh, Lavkesh Dayashankar Shri Trimurti Apt Kushwaha, Derek McPhee, Ghanshyam Maurya, Joel R. Cherry, Satinder Singh |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
biology 010405 organic chemistry Stereochemistry Chemistry media_common.quotation_subject Organic Chemistry Amorphadiene Artemisia annua 010402 general chemistry biology.organism_classification 01 natural sciences Combinatorial chemistry Yeast 0104 chemical sciences Synthetic biology parasitic diseases Chemical conversion medicine Artemisinic acid Physical and Theoretical Chemistry Artemisinin medicine.drug media_common |
| Zdroj: | Organic Process Research & Development. 21:551-558 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.6b00414 |
| Popis: | The development of a cost-effective process for the production of artemisinin, the precursor of all artemisinin-derived drugs, the first-line treatment for malaria, has been a long-pursued endeavor. The breakthrough achievement of coaxing genetically engineered yeast to express Artemisia annua genes for the commercial production of artemisinic acid, an advanced intermediate in the synthesis of artemisinin, has yet to fully realize an affordable malaria treatment for the poor because of the lack of a cost-effective chemical conversion into artemisinin. We describe herein a commercially feasible and pragmatic synthesis of artemisinin from amorpha-4,11-diene, an early-stage intermediate produced in 2-fold higher molar yield than engineered yeast cells can process into artemisinic acid. The key to this novel approach is an exceedingly effective functionalization of the isopropenyl group of amorphadiene via endo-epoxyamorphadiene to give dihydroartemisinic acid, which upon esterification followed by oxidation ... |
| Databáze: | OpenAIRE |
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