166983-58-0Relevant articles and documents
Automated process research. An example of accelerated optimization of the Friedel-Crafts acylation reaction, a key step for the synthesis of anti-HIV (+)-calanolide A
Zhang, Jintao,Kirchhoff, Eric W.,Zembower, David E.,Jimenez, Nancy,Sen, Prabir,Xu, Ze-Qi,Flavin, Michael T.
, p. 577 - 580 (2000)
An automated process research approach to reaction optimization was developed. Chemical process research can be greatly accelerated by coupling automated synthesis equipment with statistical design of experiments (DoE). With the use of an automated process approach, multiple experiments can be performed in parallel on an automated platform, and multiple parameters that may influence process performance can be examined within one set of experiments generated from statistical design. We have successfully applied an automated process research approach to optimize the Friedel-Crafts acylation reaction that was used in our total synthesis of (+)-calanolide A, a potential anti-HIV agent currently in clinical trials. The in situ yield for a coumarin product was successfully optimized, increasing from 70% to 97% by HPLC analysis.
Method for treating and preventing mycobacterium infections
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, (2008/06/13)
Calanolides and analogues thereof that demonstrate potent mycobacterium activity are provided. Also provided is a method of using calanolides and analogues thereof for treating or preventing mycobacterium infections. The calanolides and analogues thereof provided are obtained via syntheses employing chromene 4 and chromanone 7 as key intermediates.
Method for the preparation of (+/-)-calanolide A and intermediates thereof
-
, (2008/06/13)
A method of preparing (+/-)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (+/-)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (+/-)-calanolide A. A method for resolving (+/-)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing a viral infections using (+/-)-calanolide or (-)-calanolide is provided.
