Tert-Butyl urethane

Further modification on 2 at P1( P/, and IV led to several hydroxy ethylene isosteres (e.g., 6 and 7),12-14 which displayed poorer enzyme inhibitory and antiviral potencies than 2 (Table 24.1). Incorporation of the constrained 3-S-tetrahydrofuranyl urethane in place of the (V-term in us acyclic tert-butyl urethane in 2 resulted in a remarkable 10-fold increase in enzyme inhibitory potency (IC50 <0.03 nM) and more than 100-fold increase in antiviral potency (CIC95 = 3 nM).15 Although very potent, the optimized inhibitors of the hydroxy ethylene isostere series still lacked adequate aqueous solubility and acceptable pharmacokinetic profile (Figure 24.2). 

Ring closure of (3-hydroxy-a-amino acids with sulfuryl chloride/triethylamine 68 is accompanied by formation of (3-chloroalanine,16 1 whereas cyclization of urethane-protected serine and threonine by the Mitsunobu reaction 54 69 70 leads to oxazoline and dehydroalanine formation as side products. 47,71 Formation of dehydroalanine can be prevented by bulky carboxy protecting groups such as tert-butyl esters. 69 ... 

One of the earliest syntheses of r )[CH20] (methyleneoxy) peptide isosteres was reported by Rubini et alJ1,2l These authors used an intermolecular Williamsons reaction between a urethane-protected amino alcohol and tert-butyl bromoacetate (Scheme 1)J1,2] However, this method resulted in low yields and was not applicable to bulky amino acids. Thus, only isosteres containing glycine as the C-terminal component could be synthesized by this method. 

Light stable PUR 111 was created by incorporation of 4-(2,3-dihydroxyprop-oxy)-2-hydroxybenzophenone during PUR synthesis [139]. Similarly, urethane based coatings may be stabilized by immobilization of approx. 5% of 4-hydroxy-5-tert-butyl-3-[2-(5-chlorobenzotriazolyl)]methyl-isocyanate, added into the reaction mixture during PUR synthesis [140]. 

Proteases, such as thermitase,papain,f " l and subtilisinf have been employed for the deprotection of tert-butyl and methyl esters from various glycopeptides. More interestingly, the C-terminus of a nucleopeptide methyl ester 8 was deprotected selectively and in very high yield by papain.l Neither the acetate, the N-terminal urethane, the allyl phosphate, nor the phenylacetamide protection of the nucleobase were attacked (Scheme 17). 

The application of the non-urethane PhAc blocking group results in ca. 6% racemization during the construction of the phenylacetamido-protected dipeptides by chemical activation of the phenylacetamido amino acids. This disadvantage can be overcome by forming the peptide bonds enzymatically, e.g. with trypsin [26,27], chymotrypsin [26,28], or carboxypeptidase Y [26,29]. An interesting example is the biocatalyzed synthesis of leucine-enkephalin tert-butyl ester [25e], in which phenylacetamides are introduced and cleaved by means of penicillin G acylase, and the elongation of the peptide chain is carried out with papain or a-chymotrypsin. 

Polyfunctional aziridine hardeners and polyfunctional acrylates Urethane resins Cyclohexanone resin p-tert-Butyl catechol Unsaturated polyester resin... 

However, when electron-rich aryl halides were used in amidations, by-products arising from the exchange of the phenyl group ofXantPhos (11) with the aryl group of the product were observed [123]. Not only amides and enolizable amides, but also urethanes, urea derivatives, and primary and secondary sulfonamides were successfully arylated. The coupling of carbamic acid tert-butyl ester was reported by Hartwig et a. [46] in 1999 and provided N-Boc-protected anilines in one synthetic step (Scheme 13.74). 

The facile synthesis of aliphatic [ ]polyurethanes by using di-tert-butyl tricarbonate to prepare the appropriate monomers has yielded a general class of polymers. These structures are especially interesting in the context of biodegradable polymers, since the synthetic procedure is applicable to all amino alcohols with a spacer of at least four carbon atoms between the two functionalities. The reagent is the key element for the selective formation of the a,a>-isocyanato alcohol 355 intermediates for polymeric urethanes. 

The aUylcyanate 557 obtained on dehydration of 556 underwent a spontaneous 3,3-sigmatropic rearrangement to provide an aUyhc isocyanate, which on addition of tert-butylate gave rise to the highly hindered urethane 558 [203]. 

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