Kinases solid-phase synthesis

A new solid-phase synthesis of families of asymmetrically disubstituted furazano[3,4-h]-pyrazines, which overcomes selectivity problems found in solution, has been achieved by stepwise displacement of the two chlorine atoms of 5,6-dichlorofurano[3,4-b]pyrazines with nucleophiles <02TL4741>. Pyrazolo[3,4-fe]quinoxalines as a new class of cyclin-dependent kinase inhibitors have been described <02BMC2177>. 

Green, J., Solid phase synthesis of lavendustin A and analogs, J. Org. Chem., 60, 4287, 1995. Onoda, T. et al.. Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus, J. Nat. Prod., 52, 1252, 1989. 

One of the first reported solid-phase syntheses of a nonoligomeric natural product was that of lavendustin A.31 This compound is a potent tyrosine kinase inhibitor. Fortunately, the structure of this material is highly amenable to synthesis and elaboration on a solid phase. In fact, the synthesis was reported by a researcher working alone on this project (Green).31... 

Synthesis of SH3 (Src Homology Type 3) Domain from the Protein Tyrosine Kinase, c-Ahl, hy Direct Ligation on Solid Phase LFVALYDFVASGDNTLSITKGCKLRVLGYINHNGEWBEAQTKNGQWVPS-NYlTPVN-NHj ... 

Related Pd-cyclizations have been applied to the synthesis of 3-carboethoxy-2-trifluoromethylindoles [329], 2-carbobenzyloxy-4-hydroxymethyl-3-methylindoles, a unit that is present in the antibiotic nosiheptide, from a 2-(2-iodoanilino) unsaturated ester [330], 2- and 3-indolecarboxylates on solid phase [331], stephacidin A [332], an indolylquinoline KDR kinase inhibitor [333], tricyclic indoles from (2-iodophenyl)alkyl allenes [334], and 3-cyanoindoles [335], A nice vaiiation utilizes the in situ synthesis of 2-iodoanilino enamines and subsequent cyclization as shown for the preparation of indoles 322 [336],... 

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