Deprotection, microwave-assisted

In 2004, Alterman et al. used a microwave-assisted Ullmann-type protocol for the synthesis of N-(f-butyl)-3-[4-(lH-imidazol-l-yl)benzyl]-5-isobutylthiophene-2-sulfonamide (Scheme 106) [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloro-formate finally gave the target compound for biological evaluation as selective angiotensin II AT2 receptor agonist. The IH-imidazole derivative, however, showed only a low affinity for the AT2 receptor (Ki value > 10 p,M). 

Microwave-assisted epoxide ring-openings of l,5 2,3-dianhydro-4,6-0-benzyl-idene-D-allitol with nucleobases have been reported [218], Various rapid microwave-assisted protection and deprotection methods in the area of carbohydrate chemistry are known [210], and two general review articles on microwave-assisted carbohydrate chemistry were published in 2004 [219, 220]. 

Hydrogenation is widely used for deproteetion of benzyl and benzyloxycarbonyl groups. Kappe s group [67,68] deprotected benzyl esters using continuous flow and then performed comparative experiments using conventional heating and microwave assisted transfer hydrogenation, whieh resulted in lower yields (53-65%) than when eompared to flow (80-85%). 

The rapid microwave-assisted deprotection of N-benzyl carbamate (Cbz) and AT-benzyl (Bn) derivatives in solution as well as on solid support was reported by Daga et al.26 Within this report, amino groups protected as benzyl carbamates or with simple benzyl groups could be deprotected in a few minutes by microwave-assisted catalytic transfer hydrogenation with palladium charcoal in isopropanol, employing ammonium formate as the hydrogen donor (Scheme 7.6). Both MeO-PEG and PS Wang-resin were used as soluble and solid supports, respectively, in these reactions. 

Daga, M.C., Tadde, M. and Varchi, G., Rapid microwave-assisted deprotection of N-Cbzand N-Bnderivatives, Tetrahedron Lett., 2001, 42, 5191-5194. 

Similarly, Hulme and co-workers [184] have described an U-4CR under microwave-assisted conditions of an A/ -Boc-anthranilic acid, n-butylisonitrile, an aldehyde, and an amine resulting in the formation of the Ugi products 133 that were further used in the UDC-protocol (Ugi reaction-Deprotection-Cyclization) for lead finding (Scheme 103). 

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

In a effort to devise a mild, high-yielding deprotection strategy for hindered esters, Ley and Mynett [25] investigated the possibility of microwave-assisted hydrolysis of... 

The reactions with P-nucleophiles are even more rare than with C-nucleophiles. Recently such reaction was used for the synthesis of polysubstimted pyrimidi-nylphosphonic acid 172. Microwave-assisted Michaehs-Arbuzov reaction of triisopropyl phosphite with the corresponding 2-fluoropyrimidine 170, followed by deprotection of the phosphonate group using TMSBr in acetonitrile gave the desired add 172 in 66 % total yield. The derivative 172 exhibits anti-influenza virus A activity in the middle micromolar range (Scheme 37) [177]. 

The standard conditions used for microwave-assisted peptide synthesis are fairly mild, and our typical protocol for base-labile Fmoc peptide synthesis is deprotection with 20 % piperidine at 75 °C for 3 min and coupling with HBTU and DIEA at 75 °C for 5 min. Due to the temperatures used during microwave-assisted peptide synthesis there is an increased potential for unwanted side reactions. Racemization of the activated amino acid during the coupling step is a known issue even under conventional synthesis conditions and is a problem for Cys and His residues specifically. To investigate this potential problem a model 20-mer peptide that contained each of the naturally occurring amino acids was synthesized under both conventional and microwave conditions [11]. The peptides were hydrolyzed in 6N DCI/D2O, and the resulting free amino acids were subjected to GC-MS analysis to calculate the... 

Microwave-assisted organic synthesis has been found equally important to cany out some other chemical reactions like protection, deprotection, hydrolysis, esterification, cyclization, etc. 

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