Library carbamate

Sulfite paper has a relatively short life span, since residual acid will continue to hydrolyze the cellulose and cause embrittlement. Further sources of acid include aluminum sulfate (which is added together with resin to suppress bleeding or feathering of ink into the paper) and S02 and NO from the atmosphere. Much of the world s library collections and archives will soon be lost as the paper crumbles. Various deacidification treatments (e.g., with ammonia, morpholine, cyclohexylamine carbamate, or diethyl-zinc) have been proposed and tried, but at best they can only halt the process of embrittlement and cannot reverse it.14 With the move to kraft pulping, alkaline peroxide bleaching, and increasing use of precipitated calcium carbonate as a filler, the high quality papers produced today are intrinsically acid free and should also resist subsequent acidification by S02-polluted air fairly well. 

In a similar approach, Pimmg and Chen [3] prepared an indexed library of 54 carbamates from a set of nine alcohols and nine isocyanates. The library was prepared as 15 sublibraries in which each of the alcohols and isocyanates was reacted with an equimolar mixture of the other reactants. The product mixtures were tested as inhibitors of acetylcholinesterase and their activities were used as indices to the rows and columns of a two-dimensional matrix reflecting the activities of individual products. An identical approach was used by the same authors in the preparation of a library of 72 tetrahydro-acridines by the condensation of 12 cyclohexanones with six cyanoanilines in 18 sublibraries [4]. 

Biphenyl-carbamate 164d, the most active analogue of rhazinilam to date, was taken as a lead and its synthesis was re-examined for the purpose of adaptation to the construction of a library of analogues, Fig. (36) [161]. 

Positional scanning was repeatedly used by Houghten and coworkers [38] in solid-phase peptide synthesis, but few examples of its application to small molecule libraries have been reported. Smith et al. [39] deconvoluted a solid-phase library of 1600 esters/amides, Andrus et al. [40] deconvoluted a solid-phase library of non-natural polyenes, Leone-Bay et al. [41] deconvoluted the activity of an indexed library in an in vivo assay, while Pirrung et al. reported both a solution phase 54-member carbamate library [42] and a solution-phase 72-member tetrahydroacridine library [43]. 

Other isosteric replacements have also been attempted and have resulted in modest Icmt inhibitors, including secondary amines, phosphona-mides, carbamates, and triazoles (Jaimeen D. Majmudar, unpubhshed data). Secondary amines are the weakest inhibitors in this survey. The phosphona-mides and triazoles are in fact modest inhibitors, although not as potent as the SMFCs. In this library, the farnesyl hpid chain was held constant further fortifying the hypothesis that the enzyme-binding pocket is more tolerant to substitution when the key lipid recognition motif is present. 

Recently, Li etal,162 used ABPP competitive profiling to screen libraries of carbamate compounds to identify specific inhibitors for uncharacterized serine hydrolases. The carbamate reactive group reacted irreversibly with the active site serine, which, in turn, blocked subsequent labeling with a fluorescent FP probe. The carbamates were decorated with various side chains in order to find the optimal composition for dedicated target binding. Utilizing this method, a potent and selective inhibitor for a//3-hydrolase domain 6, which may play important functions in nervous system metabolism or signaling, was discovered. 

The acid-labile carbamate linkage of type 5 has also been apphed to the paraUel synthesis of a thiazolidinone library of type 12 (Fig. 2) [22], Apphcation of trityl-based resins (see Section 2.2.2.6) for this reaction sequence was not possible as the... 

Aiming to prepare a library of derivatives of the medicinally relevant piperidine scaffold, Veerman [393] and co-workers exploited N-acyhminium ion chemistry, starting from a stable aminal precursor. Coupling of six different amino acetals onto sulfonylethoxycarbonyl-modified (SEC-modified) polystyrene resin afforded the potential precursors. However, attempts to transform these into the desired piperidine derivatives via one-pot generation of N-acyliminium ions and functionalization failed, essentially because direct attack of the nucleophile on the acid-mediated oxycarbenium ion took place at a similar rate to that of the intramolecular carbamate-nitrogen attack. 

A hydantoin library of 800 compounds has been reported by Dress-mann et al. [61]. In this approach, 20 different amino acids and over 80 primary amines were incorporated. Selected amino acids were attached via their iV-terminus to hydroxymethyl polystyrene resin by using a carbamate linker. This enabled generation of the free acid resin-bound intermediates, which could then be converted to their corresponding amides by standard carbodiimide coupling reactions and excess primary amine. Concomitant... 

---