951698-14-9Relevant academic research and scientific papers
Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines
Zhang, Wu-Yan,Hogan, Philip C.,Chen, Chi-Li,Niu, John,Wang, Zhimin,Lafrance, Danny,Gilicky, Olga,Dunwoody, Nicholas,Ronn, Magnus
, p. 1784 - 1795 (2015/12/01)
A robust, cost-effective, and high yielding manufacturing process for enantiomerically enriched (S)-allylic amine 3, a key intermediate for fully synthetic tetracyclines have been developed. Two novel and scalable asymmetric vinylations resulting in high-to-excellent stereoselectivity have been developed for the key step. The final product is purified by an efficient crystallization of a l-tartaric salt. The process described has been used to manufacture ～350 kg of the tartaric salt of 3 with 99.0% ee in 8 steps (35% overall yield) from cheap and readily available dimethyl maleate.
SYNTHESIS OF ENONE INTERMEDIATE
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Page/Page column 68, (2008/12/08)
The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate.
A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics
Brubaker, Jason D.,Myers, Andrew G.
, p. 3523 - 3525 (2008/02/11)
A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics is reported. The route proceeds in nine steps (21% yield) from the commercial substance methyl 3-hydroxy-5-isoxazolecarboxylate. Key steps in the route involve enantioselective addition of divinylzinc to 3-benzyloxy-5-isoxazolecarboxaldehyde and an endo-selective intramolecular furan Diels-Alder cycloaddition reaction. The route described has provided more than 40 g of chromatographically pure 1 with 93% ee.
