174092-75-2Relevant academic research and scientific papers
PROCESS FOR PRODUCING TRICYCLIC KETONE
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Page/Page column 6; 13; 22, (2008/06/13)
In order to efficiently supply CPT, which is a starting compound of irinotecan hydrochloride and a variety of camptothecin derivatives, by a practical total synthesis, the invention provides a means of efficiently preparing a tricyclic ketone that corresp
METHOD OF SYNTHESIZING CAMPTOTHECIN-RELATING COMPOUNDS
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Page 31, (2010/02/05)
The present invention is to prepare efficiently 2'-amino-5'-hydroxypropiophenone corresponding to the AB-ring part of camptothecin (CPT) skeleton and a tricyclic ketone corresponding to the CDE-ring part in order to provide efficiently CPT by the total synthesis, which is a starting material for irinotecan hydrochloride and various kinds of camptothecin derivatives, and to provide stably CPT and its derivatives.
Solution-phase preparation of a 560-compound library of individual pure mappicine analogues by fluorous mixture synthesis
Zhang, Wei,Luo, Zhiyong,Chen, Christine Hiu-Tung,Curran, Dennis P.
, p. 10443 - 10450 (2007/10/03)
Solution-phase mixture synthesis has efficiency advantages and favorable reaction kinetics. Applications of this technique, however, have been discouraged by the difficulty in obtaining individual, pure final products by using conventional separation and
Intermediates in the synthesis of camptothecin and related compounds and synthesis thereof
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, (2008/06/13)
The present invention provides a short, convergent total synthesis of irinotecan and derivative compounds which comprises of a novel 4+1 radical annulation wherein the precursor is reacted with an aryl isonitrile having the formula wherein X is Br or I, and R4is an alkyl group, an allyl group, a propargyl group or a benzyl group, and R16is H, a C1-C6alkoxy group, a group wherein p is an integer between 4 and 12, or a C1-C12acyclic dialkylamino group. The present invention also provides novel chemical intermediates for such 4+1 radical annulations.
A general synthetic approach to the (20s)-camptothecin family of antitumor agents by a regiocontrolled cascade radical cyclization of aryl isonitriles
Josien, Hubert,Ko, Sung-Bo,Bom, David,Curran, Dennis P.
, p. 67 - 83 (2007/10/03)
A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with prop-argyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta-and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is a direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.
Kaskaden-Radikalreaktionen von Isocyaniden: eine zweite Generation der Synthese von (20S)-Camtothecin, Topotecan, Irinotecan und G1-147211C
Curran, Dennis P.,Ko, Sung-Bo,Josien, Hubert
, p. 2948 - 2950 (2007/10/03)
Keywords: Camptothecin; Isocyanide; Kaskadenreaktionen; Radikale
