Solid-phase heterocycle synthesis

Most prominent in the recent literature are papers describing the solid-phase synthesis of heterocyclic products. A review of solid-phase heterocycle synthesis has been published, focusing on the work from the Chiron group [60]. This section has been organized based on the size of the ring constructed. 

Pis 1997 Piscopio, A.D., MUler, J.F. and Koch, K., Solid Phase Heterocyclic Synthesis via Ring Closing Metathesis Traceless Liiddng and Cyclative Cleavage Through a Carbon-Carbon Double Bond, Tetrahedron Lett., 38 (1997) 7143-7146. 

Piscopio AD, Miller JF, Koch K. Solid phase heterocyclic synthesis via ring closing metathesis traceless linking and cyclative cleavage through a carhon-carbon double bond. Tetrahedron Lett. 1997 38 7143-7146. 

Burkoth, T. S., Faearman, A.T., Char-YCH, D. H., Connolly, M.D., and Zuckermann, R.N. Incorporation of unprotected heterocyclic side chains into peptoid oligomers via solid-phase submonomer synthesis. J. Am. Chem. Soc. 2003 125, 8841-8845. 

The oxazolidine-2,5-dione heterocycle, perhaps better known as the N-carboxyanhydride of an amino acid, has been incorporated employing a modification of chloromethylated poly(styrene) (192) (76USP3985715). The reaction sequence involved utilization of a masked amino acid, ethyl acetamidocyanoacetate (205). The amino acid was liberated in a subsequent hydrolysis/decarboxylation step (Scheme 98). The cyclized, IV-carboxyanhydride-functional resins (206) were reported to be useful in solid phase peptide synthesis and as supports for enzyme immobilization. 

Solid-phase asymmetric synthesis of heterocycles and heterocycles as auxiliary reagents 01 MI 126. 

Progress in application of Merrifield resin in solid phase organic synthesis including reactions with participation and formation of heterocycles 07CJ01069. 

More recently, to find more effective methods to construct bis(heterocycle)s containing a pyrimidine ring from MBH derivatives, the solid-phase parallel synthesis of new annulated pyrimidinone derivatives was disclosed (Scheme 4.219). " The resin-bound allyl amine derivatives 742 were treated with cyanogen bromide to yield the pyrazole derivatives 743 in good yields under standard conditions. The subsequent lactonization with cleavage of the resin afforded the pyrimidinone derivative 744 in good yields in the presence of 20% triethylamine in chloroform under reflux. 

Cyclo-release strategy in solid-phase combinatorial synthesis of heterocyclic skeletons 12AHC(107)41. 

V. Krchnak, J. Smith, J. Vagner, Solid-phase traceless synthesis of selected nitrogen-containing heterocyclic compounds. The Encore technique for directed sorting of modular solid support. Collect. Czech. Chem. Commun. 2001, 66, 1078-1106. 

Since the introduction of solid-phase peptide synthesis by Merrifield (1) nearly forty years ago, solid-phase techniques have been applied to the construction of a variety of biopolymers and extended into the field of small molecule synthesis. The last decade has seen the emergenee of solid-phase synthesis as the leading technique in the development and production of combinatorial libraries of diverse compounds of varying sizes and properties. Combinatorial libraries can be classified as biopolymer based (e.g., peptides, peptidomimetics, polyureas, and others [2,3]) or small moleeule based (e.g., heterocycles [4], natural product derivatives [5], and inorganie eomplexes [6,7]). Libraries synthesized by solid-phase techniques mainly use polystyrene-divinylbenzene (PS) derived solid supports. Owing to physieal and ehemical limitations of PS-derived resins, other resins have been developed (8,9). Most of these resins are prepared from PS by functionalizing the resin beads with oligomers to improve solvent compatibility and physical stability (8,9). 

Fig. 1 Synthetic approaches towards peptoids by either (a) solid-phase submonomer synthesis or (b-d) ring-opening polymerization initiated by nucleophiles such as (b) amines in solution, (c) amines on solid-phase resins, or (d) IV-heterocyclic carbenes in solution...

B.B. Mishra, D. Kumar, A. Mishra, P.P. Mohapatra, V.K. Tiwari, Cydo-release strategy in Solid-phase combinatorial synthesis of heterocyclic skeletons, Adv. Heterocycl. Chem. 107 (2012) 41-99. 

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