Trityl protection with

It has been shown that glyeine amides of aminobenzophenones are readily converted to the corresponding benzodiazepines in vivo. Peptides which terminate in such a moiety should thus serve as a benzodiazepine prodrug after hydrolysis by peptidases. One of the glycine residues in lorzafone (194)is presumably removed metabolicaUy in this manner to give a benzodiazepine precursor which spontaneously cyclizes. Acylation of benzophenone 190 with the trityl protected dipeptide 191, as its acid chloride 192, affords the amide 193. Removal of the trityl protecting group with acid yields lorzafone (194) [50]. 

In subsequent studies,22 Sheehan et al. demonstrated that the action of diisopropylcarbodiimide on penicilloate 24, prepared by protection of the free primary amino group in 23 with trityl chloride (see Scheme 6b), results in the formation of the desired -lactam 25 in a very respectable yield of 67 %. In this most successful transformation, the competing azlactonization reaction is prevented by the use of a trityl group (Ph3C) to protect the C-6 amino function. Hydrogenolysis of the benzyl ester function in 25, followed by removal of the trityl protecting group with dilute aqueous HC1, furnishes 6-aminopenicillanic acid (26), a versatile intermediate for the synthesis of natural and unnatural penicillins. 

Using method a, oligodeoxyribonucleotides were synthesized from di- to deca-deoxyribonucleotides by means of mesitylenesulfonylimidazole and mesitylenesulfonyl-1,2,4-triazole. With triisoproylbenzenesulfonylimidazole die condensation took place more slowly.11121 Compared widi the corresponding arylsulfonyl chlorides, imidazolides induced intemucleotide condensation much more slowly, but caused no darkening of the reaction mixture, did not affect acid-sensitive bonds in trityl protected nucleotides, and did not sulfonate the 3 -hydroxy groups.11111 The reaction conditions were room temperature, 5—6 days, and pyridine as solvent.11111... 

To create the free secondary amine group (N-H) fulleropyrrolidine, an amine-protected starting material can be used in the reaction (Cai et al., 2006). For instance, a trityl-oxazolidinone (using either triphenylmethyl- or better, 4-methoxytriphenylmethyl-protecting groups) can be reacted with C60 to yield the trityl-protected pyrrolidine (Figure 15.5). 

Remove the trityl-protecting group by dissolving the derivatized fulleropyrrolidine in 5 ml of dichloromethane in a fume hood and then adding 50 pi of TFMSA (caution ) with stirring. 

Figure 15.5 A trityl-protected pyrrolidine derivative of Cgg can be prepared by the reaction of N-trityl-oxazolidinone with a fullerene. Deprotection of the trityl group using methanesulfonic acid gives the secondary amine, which can be used in further conjugation reactions.

In the second procedure13 (see Scheme 3), D-glucitol (10) was converted into 5-O-benzoyl-1,3 2,4-di-O-ethyl idene-6-O-trityl-D-glucitol (17) by successive treatment with acetaldehyde to produce 15, with chlorotriphenylmethane to provide 16, and with benzoyl chloride to afford 17. Selective removal of the trityl protecting group from 17, to give 18, followed by oxidation of 18, provided 19 which, on hydrolysis, afforded L-gulose (9). 

Still, with ester groups, triethylamine is sufficient to catalyze the isomerization, as shown with the trityl-protected example 71 [130] (Scheme 1.31). 

Alternatively to using prelipidated building blocks palmitoylation on resin is possible with the hydrazine linker. In Scheme 27 the synthesis route for the palmitoylated and farnesylated N-Ras peptide 78 is shown. Here the initial loading of trityl-protected cysteine to the hydrazine linker was mediated by A,A-diisopropylcarbodiimide (DIG) and HOBt. After Fmoc removal the proline was coupled using HBTU and HOBt. The trityl-protected dipeptide 75 was subsequently S-deprotected using TFA with triethylsilane (TES) as a scavenger. Farnesylation of the free thiol was achieved with an excess of farnesyl bromide. 

The cyclization of a peptide with an N-terminal 3-hydroxy-a-amino acid is generally performed via the O-mesyl or O-tosyl derivatives. Again the course of the cyclization reaction is governed by the N-terminal protecting group and best results are obtained with Al-trityl protected seryl/threonyl peptides. 

Halogen atoms have been placed at C-6 of substituted 6-deoxy-hexoses by a variety of interesting ways, and the products provide potential routes to 6-deoxyhexoses. Helferich and coworkers 4 reported a low yield of methyl 6-chloro-6-deoxy-a-D-glucoside which they prepared by reaction of the (suitably protected) corresponding 6-trityl ether with phosphorus pentachloride. Sinclair 44 has provided a convenient procedure for the preparation of the 6-chloro derivative in yields of 30-35% by allowing methyl a-D-glucopyranoside to react with sulfur monochloride, SjClj, in N,/V-dimethylformamide. A much better yield (73%) of the 6-bromo derivative was reported1 in the reaction of methyl 2,3,4-tri-O-benzoyl-6-O-trityl-a-D-altroside with phosphorus tribromide and bromine. 

The employment of trityl trifluoroborate is particularly interesting. This reagent is able to introduce trityl groups on both primary and secondary alcohols54 and to selectively oxidize secondary trityl ethers to ketones in the presence of primary trityl ethers.55 Thus, treatment of diols with trityl trifluoroborate leads to tritylation of both alcohols followed by oxidation of the secondary trityl ether, resulting in the formation of a ketone possessing a trityl-protected primary alcohol. A work-up by mild acidic hydrolysis provides the deprotection of the primary trityl ether and formation of a hydroxy ketone.54... 

The trityl-protecting group was removed by treatment of the 480 teabags with 2% TFA in DCM (twice for 10 min). 

Synthesize the peptides with side-chain-unprotected hydroxy amino acids (see Note 14) or amino acids with selectively cleavable side-chain-protecting groups (such as trityl cleaved with 1 to 5% TFA in dichloromethane at room temperature for 1 h [11]) in each position to be modified. 

The three orthogonally removable lysine protecting groups we use here are Fmoc (9-fluorenyl methoxy carbonyl), cleavable with 20% base, preferably with 20% piperidine or 3% DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (18), Dde (1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-ethyl), cleavable with 2% hydrazine, and Aloe (allyloxy carbonyl), cleavable with palladium. Hydrazine also removes Fmoc, and thus it can be applied only if no Fmoc groups are present on the growing peptide chain. Acid-sensitive amino protecting groups available are Boc (tert-butyloxy carbonyl), cleavable with 90% TFA, and Mtt (4-methyl-trityl), cleavable with 1% TFA. We use Boc for the protection of the N-terminal moieties of N-terminal amino acids in each peptide chain as well as at the N-terminus of the scaffold. 

Lew and Kim [66] recently synthesized a sulfide isostere of carbocyclic influenza neuraminidase inhibitor 268, moving from trityl protected aziridine 266, in turn prepared from (-)-quinic acid 159 (Scheme 43). Ring opening of 266 with 1-propanethiol promoted by BF3 etherate, followed by acetylation, gave sulfide 267 which was finally hydrogenated to diamine 268, in a good chemical yield. As the authors expected, mercapto-derivative 268 resulted to be a strong inhibitor of... 

N-Tritylamino acids. Direct reaction of trityl chloride with amino acids provides N-trityl derivatives in low yield. A superior route to these derivatives involves reaction of trimethylsilyl esters of N-trimethylsilylamino acids with trityl chloride in refluxing chloroform, which provides the N-protected amino acids in 88-92% yield. Trimethylsilyl-protected hydroxyl or thiol groups are not cleaved under these conditions.1... 

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