125573-72-0Relevant academic research and scientific papers
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.
GAS-PHASE REACTIONS OF ARYLSILANES WITH NITRATING CATIONS. NITRATION vs. NITRODESILYLATION
Attina, Marina,Cacace, Fulvio,Ricci, Andreina
, p. 217 - 224 (2007/10/02)
The mass spectrometric and radiolytic study of the reaction of (MeNO3)H(+) with phenyl- and tolyl-trimethylsilanes has allowed to demonstrate the first example of gas-phase aromatic nitro desilylation.The process accompanies predominant nitration of the substrate, the ratio of the two channels ranging from ca. 1:2 in the case of C6H5Si(CH3)3 to ca. 1:4 in the case of m-CH3C6H4Si(CH3)3, measured in CH4 at 37 deg C, 750 Torr.Nitro desilylation of trimethylsilanes gives nitrotoluenes in which the NO2 group is not exclusively bound to the ring position formerly occupied by the SiMe3 group.Such observation bears directly on an unsettled problem concerning the detailed course of aromatic substitution by gaseous (RNO3)H(+) ions, in that it favours the classical pathway, involving intermediacy of arenium ions, excluding the alternative, concerted mechanism.The gas-phase nitration of C6H5Si(CH3)3 is characterized by a kPhSiMe3/kPhH ratio of 6.5 +/- 0.5 and by a 25percent ipso, 28percent ortho, 23percent meta, 24percent para orientation.These data can be combined with the known ρ constant of the reaction to derive the SiMe3 substituent constants, i. e. ?m(+) = -0.17 and ?p(+) = -0.25.The mechanistic features of the gas-phase reactions of (MeNO3)H(+) with phenylsilanes are discussed, and compared with relevant data from condensed-phase studies.
