64725-24-2Relevant articles and documents
Studies on Rubia akane (RA) derivatives. Part 8. Design, syntheses and antitumour activity of cyclic hexapeptide RA analogues possessing an alkyl substituent on the Tyr-3 aromatic ring
Hitotsuyanagi, Yukio,Lee, Suguru,Ito, Izumi,Kondo, Kazuyuki,Takeya, Koichi,Yamagishi, Takehiro,Nagate, Takatoshi,Itokawa, Hideji
, p. 213 - 217 (2007/10/03)
The effective conversion of RA-VII 1 into the naturally less-accessible RA-II 4 has been devised through boron tribromide bis-O-demethylation and successive selective partial O-methylation using diazo(trimethylsilyl)methane. The O-triflate 11 prepared from RA-II 4 was subjected to cross-coupling reaction with alkylstannanes to produce analogues 12, 13 and 15, while compounds 13 and 15 were later converted into analogues 14 and 16, respectively. Analogues 12-16 showed antitumour activity against P-388 leukaemia both in vitro and in vivo.
Total synthesis of cycloisodityrosine, RA-VII, deoxybouvardin, and N29-desmethyl-RA-VII: Identification of the pharmacophore and reversal of the subunit functional roles
Boger, Dale L.,Yohannes, Daniel,Zbou, Jiacheng,Patane, Michael A.
, p. 3420 - 3430 (2007/10/02)
Full details of a concise total synthesis of RA-VII (1) and deoxybouvardin (2) are described based on the implementation of an effective intramolecular Ullmann reaction as the key macrocyclization reaction in the preparation of the elusive 14-membered cycloisodityrosine subunit (33) of the bicyclic hexapeptides. Subsequent coupling of 34 to tetrapeptide 17 and macrocyclization with C2-N3 amide bond formation provided 1 and 2. In efforts that address the key structural and conformational features of the agents that contribute to their antitumor activity, N29-desmethyl-RA-VII was prepared and its chemical, conformational, and preliminary biological properties are detailed. The comparable conformational features of N29-desmethyl-RA-VII and RA-VII including a characteristic cis C30-N29 amide bond suggest that the tetrapeptide housed within the 18-membered ring induces the 14-membered cycloisodityrosine to adopt a conformation possessing an inherently disfavored cis secondary or tertiary amide. Moreover, in contrast to prior suppositions in which the rigid 14-membered ring of N-methylcycloisodityrosine has been suggested to serve the functional role of inducing a rigid, normally inaccessible conformation within the biologically relevant D-Ala-Ala-N-Me-Tyr-(OMe)-Ala tetrapeptide, experimental studies demonstrating that the intrinsic activity of the agents resides within the cycloisodityrosine subunit are presented. Thus, the results of the experimental studies require a reversal of the functional roles of the subunits of the agents in which it is the tetrapeptide housed within the 18-membered ring that potentiates the inherent biological properties and alters the conformation of cycloisodityrosine.
The first total synthesis of deoxybouvardin and RA-VII, novel antitumor cyclic hexapeptides
Inaba,Umezawa,Yuasa,et al.
, p. 2957 - 2958 (2007/10/02)
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