- Synthesis of combretastatin A-4 prodrugs and trans-isomers thereof
-
The present invention relates to novel water-soluble, stable derivatives of combretastatin A-4, and novel synthesis methods therefore. The combretastatin A-4 prodrugs described herein appear to be useful in the treatment of neoplastic disease.
- -
-
Page/Page column 9
(2008/06/13)
-
- The study of phosphoramidite as O-phosphitylation agent and its reactivity
-
O-phosphorylated peptide and amino acid are important in living system. In this paper, Dialkyl-N,N-dialkyl phosphoramidites (DDPA) 3 were synthesized using two methods. The reaction of DDPA with the hydroxyl group of the corresponding amino acids in the presence of tetrazole, followed by oxidation, gave O-phosphoryl amino acid methyl esters in a good yield. A systematical study of the reactivity of DDPA was presented too.
- Chen, Shui-Bing,Li, Yan-Mei,Luo, Shi-Zhong,Zhao, Gang,Tan, Bo,Zhao, Yu-Fen
-
p. 277 - 291
(2007/10/03)
-
- Kinetics and mechanism of tetrazole-catalyzed phosphoramidite alcoholysis
-
Kinetics of the tetrazole-catalyzed reaction of diisopropyl N,N-diisopropylphosphoramidite (1b) with tert-butyl alcohol has been studied by 31P NMR spectroscopy in THF, and the results obtained have been compared to those observed for the possible partial reactions involved, viz. the formation of diisopropyl tetrazolylphosphite (2b) and its subsequent alcoholysis. The stoichiometry of the processes was first examined with dimethyl N,N-diisopropylphosphoramidite (1a) in MeCN. The tetrazole-promoted disappearance of 1b is as fast in the absence and in the presence of the alcohol: the alcoholysis of 1b is zero-order in the concentration of alcohol and second-order in the concentration of tetrazole. The reaction of 1b with tetrazole is independent of the concentration of the tetrazolide anion and second-order in that of tetrazole, while the reverse reaction, aminolysis of 2b is first-order in the concentration of the amine The alcoholysis of 2b is, in turn, first-order in the concentration of alcohol and second-order in that of tetrazole, but it also proceeds, although slowly, in the absence of tetrazole. The time-dependent product distribution of the alcoholysis of 1b shows intermediary accumulation of 2b, but at a lower level than could be predicted by applying the rate constants determined independently for the assumed partial reactions. Accordingly, tetrazole-catalyzed alcoholysis of 1b is shown to proceed at least mainly via 2b, but an additional pathway not involving 2b as an intermediate is proposed. Mechanisms of the partial reactions are discussed on the basis of the formal kinetics observed.
- Nurminen, Erkki J.,Mattinen, Jorma K.,Loennberg, Harri
-
p. 1621 - 1628
(2007/10/03)
-
- Alternative Strategies for the Fmoc Solid-Phase Synthesis of O4-Phospho-L-tyrosine-Containing Peptides
-
A number of biologically relevant O4-phospho-L-tyrosine-containing peptides have been synthesized by either the global phosphorylation of the side-chain-unprotected L-tyrosine moiety in presynthesized resin-bound peptides or alternatively by the incorporation of suitable protected O4-phospho-L-tyrosine building blocks in the continuous-flow method of Fmoc solid-phase peptide synthesis.Different phosphate-protecting groups have been applied.
- Kitas, Eric A.,Knorr, Reinhard,Trzeciak, Arnold,Bannwarth, Willi
-
p. 1314 - 1328
(2007/10/02)
-
