Purine library

M., Leary, J. A., Bertozzi, C. R. (2001) Discovery of estrogen sulfotransferase inhibitors from a purine library screen. J Med Chem 44, 2683-2686. 

In another purine library synthesis, Schultz and co-workers attached a 6-aminomethylaniline side chain to the PAL linker1718 via reductive amina-tion (Scheme 5). Alkylation at the 9-position was achieved using Mitsunobu conditions and an SwAr reaction was used to functionalize the 2-position with amines. The final cleavage of the aniline was achieved using 90%... 

The group of Schultz has synthesized a 406-member purine library on MD grafted SynPhase Crowns with varying substituents at the C2 and C6 positions.29 A common 2-chloropurine derivative was coupled onto... 

Schultz and co-workers31 also described the preparation of a 2,6,9-trisubstituted purine library. A preformed 2-fluoro-6-(4-aminobenzylamino) purine was reductively aminated onto the BAL linker 12. Mitsunobu chemistry was employed to alkylate the C9 position on the support-bound intermediate (Scheme 4). Subsequently, SNAr chemistry was used to incorporate amines at C6. The newly introduced primary and secondary amines bear diverse functional groups and the Mitsunobu reaction allows for incorporation of primary and secondary alcohols lacking acidic hydrogens. The support-bound product 13 was cleaved with 90% TFA/10% H20 to give a library with HPLC purities ranging between 51 and 85%. 

Figure 8 Three biologically active compounds from target class purine libraries directed at protein kinases...

R. Sarohia, M. Leost, L. Meijer, P. G. Schultz, Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors, Chem. Biol. 1999, 6, 361-375. 

Compound source Library size DOS of purine library 1,561... 

One-pot synthesis of 6-mercaptopurines from 4,5-diamino-6-chloropurine, an aldehyde and elemental sulfur has been reported. The key advantage of this procedure is that H2S was generated in situ <04TL2321>. An efficient conversion of 6-cyanopurines into 6-alkoxyformimidoylpurines has been developed <040BC1019>. Synthesis of diverse purine libraries has been optimized by a microwave assisted method using minivials <04JCO171>. 

Combs P, Takvorian AG (2004) Microwave-assisted organic synthesis using minivials to optimize and expedite the synthesis of diverse purine libraries. J Comb Chem 6 171-174... 

A regiospecific strategy to A-7-substituted purines 65 and its application to a library of 2,6,8-trisubstituted purines has been reported. The three-step synthetic strategy involves cyclization reactions of suitably substituted pyrimidines 63 with either a carboxylic acid or an aldehyde <06JC0410>. 

X., Schultz, P. G. (2002) Resin-capture and release strategy toward combinatorial libraries of 2,6,9-substituted purines. J Comb Chem 4, 183-186. (b) Ding, S., Gray, N. 

Schultz and co-workers have described a crown-based synthesis of 406 purines varying at the C-2 and C-6 positions.14 This library was targeted for... 

Scheme 4 outlines an alternative synthesis of a library of disubstituted purines by a strategy similar to that shown in Scheme 315 except that... 

To expand the diversity of their libraries Brill et al.16 also modified various heterocycles by alkylation, acylation, or metal-mediated coupling reaction prior to resin capture. A remaining chloro substituent was still available for nucleophilic displacement or a palladium-mediated coupling reaction with anilines, phenols, and boronic acids on solid phase [see Fig. 10 for the preparation of purine derivative (62)]. 

Traceless solid-phase synthesis of 2,6,9-trisubstituted purines from resin-bound 6-thiopurines <02T7911>, and microwave assisted solid-phase synthesis of 2,6,9-trisubstituted purines <02TL6169> have been described. A resin-capture and release strategy toward combinatorial libraries of 2,6,9-trisubstituted purines has been reported <02JCO183>. Alkylated purines chlorinated at the 6,8- or 2,6,8-positions can be captured onto a solid support and further elaborated by aromatic substitution or via palladium catalyzed crosscoupling reactions <02JA1594>. 

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