METHODS AND SYSTEMS FOR CAMPTOTHECIN ANALOG SYNTHESIS

摘要

Methods and systems for making camptothecin analogs and intermediates are provided. Aspects include safer and lower cost methodologies for making camptothecin analogs and intermediates from synthetic materials. In another aspect, the methods and systems can achieve a yield of the camptothecin analogs greater than about 0.4%.

主权项

1. A method of making the compound of Formula II comprising:
forming AP4622-1 from propane-1,3-dithiol and 3-hydroxybenzaldehyde; adding a solution of TBSC1 to a solution of AP4622-1 and imidazole to form AP4622-2; adding n-BuLi to a solution of AP4622-2 to form a first mixture and adding TBSC1 to the mixture to form AP4622-3; adding a solution of AP4622-3 to a solution of NBS to form AP4622-4; adding tetrabutylammonium fluoride trihydrate to a solution of AP4622-4 to form AP4622-5; adding HNO3 to a solution of AP4622-5 to form AP4622-6; adding tin powder to a mixture of AP4622-6 to form AP4622; and combining AP4622, s-Trione, in the presence of TsOH to form AR67.