Deprotection procedures

2 Most texts describing peptide synthesis use the term racemisation when referring to loss of chirality at one chiral centre when two or more chiral centres are present. Benoiton (1994) has pointed out that this practice is incorrect and that enantiomerisation should be used. 

Enantiomerisation can be detected by using an analytical procedure such as HPLC with high resolution and sensitivity to separate and quantify diastereoiso- 

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Phosphate triesters (18) are iatermediates ia both the phosphotriester and phosphoramidite methods, and under appropriate conditions for deprotection of the bases and cleavage of the support, can be obtained directiy by usiag these approaches. The ethyl and isopropyl esters have been obtained directiy by usiag the phosphoramidite method because these are stable duting the normal deprotection procedure (62). By changing the oxidizing agent to Sg, both amidate and triester thiolates can be obtained. 

This amide, readily formed from an amine and the anhydride or enzymatically using penicillin amidase, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides, phosphorylated peptides, and oligonucleotides, as well as on nonpeptide substrates. The deprotection of racemic phenylacetamides with penicillin acylase can result in enantiomer enrichment of the cleaved amine and the remaining amide. An immobilized form of penicillin G acylase has been developed. ... 

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 quest for a solvent-free deprotection procedure has led to the use of relatively benign reagent, ammonium persulfate on silica, for regeneration of carbonyl compounds (Scheme 6.10) [48]. Neat oximes are simply mixed with solid supported reagent and the contents are irradiated in a MW oven to regenerate free aldehydes or ketones in a process that is applicable to both, aldoximes and ketoximes. The critical role of surface needs to be emphasized since the same reagent supported on clay surface delivers predominantly the Beckmann rearrangement products, the amides [49]. 

A Surovoy, JW Metger, G Jung. Optimized deprotection procedure for peptides containing multiple Arg(Mtr), Cys(Acm), Trp and Met residues, in CH Schneider, AN Eberle, eds. Peptides 1992. Proceedings of the 22nd European Peptide Symposium, Escom, Leiden, 1993, pp 241-242. 

H Yajima, N Fujii. Acidolytic deprotecting procedures in peptide synthesis, in The Peptides Analysis, Synthesis, Biology, Vol. 5, pp 65-109, Academic Press, New York, 1983. 

By employing coordination complexes as branch points, dendrimers can be synthesized that contain metal ions throughout their structure. The repetitive unit of such dendrimers contains M-C, M-N, M-P, or M-S bonds [53,62]. The metal ions act as supramolecular glue [63], in which the complexation chemistry directs the assembly and structure of the dendrimer [53]. One of the synthetic procedures used to prepare organometallic dendrimers with coordination centers in every layer is based on a protection/deprotection procedure in which two complexes are used as dendritic building blocks wherein one acts as a metal and the other as a ligand [64,76]. 

The deprotection procedure is based on transesterification of benzyl phosphate into the corresponding silyl ester followed by hydrolysis or alcoholysis. 

Most frequently, sugar O-acetates have been used in N-linked glycopeptide synthesis. The protection of the glycosylamines as O-acetates requires two steps in the deprotection procedure after glycopeptide assembly. 

Of all the selective, deprotection procedures that are available to carbohydrate chemists, the partial hydrolysis of polyacetals is probably the most familiar. Articles by de Beider4,5 and Brady6 contained examples of this type of reaction for aldose and ketose derivatives, respectively, and an article by Barker and Bourne7 gave useful information from the early literature on the graded, acid hydrolysis of acetal derivatives of polyols. A discussion of the stereochemistry of cyclic acetals of carbohydrates was included in an article by Mills 70 and in one by Ferrier and Overend,76 and a survey of the formation and migration of carbohydrate cyclic acetals was made by Clode.7c... 

Interestingly, application of the selective deprotection procedure to cycloheptaamylose did not give satisfactory results, a large number of products being produced. However, in this case, the direct approach afforded the heptakis(6-azido-6-deoxy)cycloheptaamylose [as its hepta(2,3-diacetate)] in 57% yield, that is, over twice the yield for the corresponding reaction on cyclohexaamylose. The different outcome of these two reactions when applied to the two closely related cyclo-oligosaccharides illustrates the subtle factors that may influence relative reactivity in complex molecules. 

The protection-deprotection procedure of the nitrogen atom of 2-azetidinones holds a prime position in synthetic methodologies leading to functionalized (3-lactam derivatives. 

The use of masked acyl anion equivalents in a synthetic protocol requires additional steps to unmask the carbonyl unit. Sometimes the deprotection procedures are incompatible with sensitive compounds thus, a direct nucleophilic acylation protocol is desirable. While C-nucleophilic carbonyl groups do not... 

Thirdly, some of the derivatives provide protection of the functional group, and their preparation, chemical reactivity, and deprotection procedures may be of value in the design of synthetic strategies. 

Majoral et al.1114 reported the facile divergent synthesis of a novel P-dendrimer series (Scheme 4.27). Treatment of the sodium salt of 4-hydroxybenzaldehyde (100) with trich-lorothiophosphorus(V) gave the trialdehyde 101, which, when treated with three equivalents of the hydrazine derivative 102, quantitatively afforded the first generation dendrimer 103 possessing six P-Cl bonds juxtaposed for repetition of the sequence. Construction of the second, third, and fourth (104) generations followed this iterative sequence. Key features of this sequence included no protection-deprotection procedures and the... 

Fig. 2.21. Acid catalysed SN1 substitutions of trityl ethers to trityl alcohols, using deprotection procedures from nucleotide synthesis as an example. The table in the center indicates the time (t) it takes to completely cleave the respective trityl groups.

The corresponding silyl ethers are stable under the usual conditions employed in organic synthesis for the deprotection of silyl groups and were deprotected using photolysis at 254 nm in yields ranging from 62-95%. Therefore, the hydrosilylation of ketones and aldehydes followed by this deprotection procedure is formally equivalent to the reduction of carbonyl moieties to the corresponding alcohols. 

C02Me, etc.) were formed in good yield. A short and high-yielding synthesis of showdomycin 133 (Scheme 34) illustrated the utility of the method.88 D-Ribose was converted to the known derivative 134 which, on mesylation and displacement with anisyltelluride anion, gave 135. Methyl radical exchange on 135 in the presence of maleimide gave 136 which, on oxidation to sulfoxide and elimination, afforded the derivative 137. Standard deprotection procedures readily transformed 137 into the antibiotic showdomycin 133. The overall yield was about 30%. 

The combined catalyst of Sc(OTf)3 and distannoxane gives the one-treatment process. Namely, in the reaction of ro-hydroxy alkanal, one-pot aldehyde allylation and acetylation of a primary alcohol are achieved without protection/ deprotection procedures. The unwanted acetylation of a secondary homoallyl alcohol by Sc(OTf)3 is suppressed by hybridization with distannoxane (Equation (46)).151... 

This amide, readily formed from an amine and the anhydride,1 is readily cleaved by penicillin acylase (pH 8.1, N-methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides2 as well as on nonpeptide substrates.3... 

Without doubt, the solid-phase peptide synthesis (Merrifield method) remains a preferred method for controlling all five critical molecular design parameters (size, shape, topology, flexibility, and surface chemistry) by precisely producing amino-acid sequences in a stepwise fashion. The scope and limitations of this approach have been reviewed [34] and widely recognized [35]. These solid-phase syntheses with protection/deprotection procedures are used routinely to produce numerous, previously unattainable [36], polypeptides and polynucleotides. One of the ultimate synthetic efforts in the control of CMDPs was the total synthesis by Khorana et al. [37] of a DNA molecule in the 1960s. 

Preparation of 6-[(2-aminomethyl)phenyl]-2-(2-pyridin-2-ylethyl)amide (General Deprotection Procedure)... 

S,5R)-2-(Diphenylmetboxy)-3,3-dimethyl-7-spiro[cyclo-propane-l,6-[4]tbia[l] azabicyclo[3.2.0]-beptane]-2-carboxylic acid, 4,4-dioxide (General dipbenylmetbyl ester deprotection procedure)... 

Apart from the above-mentioned deprotection procedures, photolytic deprotectionh l or electrochemical proceduresf - have been proposed. 

N -Protection as allyl carbamate is used generally only for specific synthetic purposes where acid- or base-mediated deprotection procedures must be avoided or reduced to a minimal extent as in the case in the synthesis of glyco- and phosphopeptides (see Sections 6.3 and 6.5). Otherwise the orthogonality of this type of amino protection has been mainly exploited in side-chain protection to allow for selective chemistry such as selective acylations, e.g. cyclizations, to be performed on protected peptides in solution or in the resin-bound state (see Section 4.3.2.3.4). An additional interesting application of the Aloe group is the one-pot deprotection and acylation with carboxy components resistant to the paUadium(0)-catalyzed allyl cleavage by hydrostannolysis as reported in Section 4.3.2.3.4.P 1... 

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