Unmasking

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Acetylene is also protected as propargyl alcohol (300)[2H], which is depro-tected by hydrolysis with a base, or oxidation with MnOi and alkaline hydrolysis. Sometimes, propargyl alcohols are isomerized to enals. Propargyl alcohol (300) reacts with 3-chloropyridazine (301) and EtiNH to give 3-diethylami-noindolizine (303) in one step via the enal 302[2I2]. Similarly, propargyl alcohol reacts with 2-halopyridines and secondary amines. 2-Methyl-3-butyn-2-ol (304) is another masked acetylene, and is unmasked by treatment with KOH or NaOH in butanol[205,206,213-2l5] or in situ with a phase-transfer cata-lyst[2l6]. 

In a more elaborate and specific synthesis, the terpenoid indole skeleton found in haplaindole G, which is isolated from a blue-green alga, was constructed by addition of a nucleophilic formyl equivalent to enone 6.5A. Cyelization and aromatization to the indole 6.6B followed Hg -catalysed unmasking of the aldehyde group[6]. 

Acid-C t lyzed Chemistry. Acid-catalyzed reactions form the basis for essentially all chemically amplified resist systems for microlithography appHcations (61). These reactions can be generally classified as either cross-linking (photopolymerization) or deprotection reactions. The latter are used to unmask acidic functionality such as phenohc or pendent carboxyhc acid groups, and thus lend themselves to positive tone resist apphcations. Acid-catalyzed polymer cross-linking and photopolymerization reactions, on the other hand, find appHcation in negative tone resist systems. Representative examples of each type of chemistry are Hsted below. 

A eommon approaeh starts with a proteeted 1,4-diearbonyl and unmasks the requisite earbonyl using aeid, thus faeilitating the Paal-Knorr reaetion immediately upon deproteetion. For example, Nagai used sulfurie aeid to eonvert aeetal 77 into 2,4-disubstituted furan 78 albeit in low yield.Molander produeed a different 2,4-disubstituted furan by a similar strategy. Thioketal aeetal 79 was treated with mereury(II) ehloride and furnished furan 80 in 71% yield. Thus this strategy provides a useful approaeh for the synthesis of a variety of 2,4-disubsituted furans. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

Most pyridines are reduced to the corresponding piperidines, but certain substituents, notably 2-amino and 2-hydroxy, tend to arrest the hydrogenation at the tetrahydro stage (55,56 7). Wenkert et ai. (llS) noted that in hydrogenation of any aromatic system capable of unmasking a stable, vinylogous amide unit, absorption may cease at this stage. An example is reduction of 3-acetylpyridine (I) to 2, a compound that resisted further attempts at reduction (31). 

A formal total synthesis of the prostaglandin involved unmasking of an isoxazoline ring by hydrogenation over W-2 Raney Ni/BCl3/MeOH, H2O to reveal a -hydroxyketone. It was necessary in this case to deactivate the Raney... 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

The clinician must be cautious in interpreting some of these symptoms (especially anxiety) in patients withdrawing from benzodiazepines. Anxiety fearfulness, and dysphoria may represent symptoms that were treated by the benzodiazepine and unmasked on withdrawal. 

The choice of the acyl substituent X for Diels-Alder reactions of l-N-acylamino-l,3-butadicnes depends on the particular synthetic problem. The acyl substituent has a moderate effect on the cycloaddition reactivity of these dienes, and also determines what amine unmasking procedures are required. As a result of their stability and the variety of amine deprotection procedures available, " the diene carbamates are the components of choice in most cases. A particularly attractive aspect of the diene synthesis detailed here is the ability to tailor the amino-protecting group... 

The influence of iron(III) salts on coupling reactions of alkynes and aldehydes (Scheme 10, routes B and C) was also explored. In these routes, a new stereoselective coupling of alkynes and aldehydes was unmasked, which led to ( ,Z)-1,5-dihalo-1,4-dienes (route B, Scheme 10) and/or ( )-a,p-unsamrated ketones (route C, Scheme 10) [27]. 

It is obvious that strenuous efforts have been invested in the research of 5-HT receptors and, in particular, in the development of receptor-selective agonists and antagonists. All this has been done in the hope that it might be possible to control a specific switch in the brain that governs a particular aspect of 5-HT function and which would be beneficial therapeutically. A further ambition is that, by avoiding activation of other 5-HT receptors, the risk of any unwanted side-effects would be eliminated. Of course, it is equally possible that reduction in non-specific receptor interactions could actually unmask some side-effects. 

According to Mata et al, [309], solubilization in Ci2Eg solution unmasked the inhibitory effect of several antibodies (B/3D6, Y/1F4, Y/2EG, Y/3G6, B/4H3, A/4H3 and I/2H7) on the Ca -ATPase, They suggested that these antibodies bind to protein-protein contact sites opened by the dissociation of ATPase oligomers, thus causing inhibition. Alternatively, the binding of antibody to the solubilized ATPase may promote its folding into a conformation that is unfavorable for enzymatic activity. 

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