Protective Group Removal

In this reaction the fully acetylated sugar 5- or 6-phosphates were phos-phorylated and the protecting groups removed by alkali. Only a-1-phosphates were isolated and no evidence of the -anomers could be detected. 

G Barany, RB Merrifield. A new amino protecting group removable by reduction. 

Knudsen, K.R. and Holden, J. and Ley, S.V. and Ladlow, M. (2007). Optimization of Conditions for 0-Benzyl and A-Benzyloxycarbonyl Protecting Group Removal using an Automated Flow Hydrogenator. Synth. Catal, 349, 535-538. 

Steps making use of systems containing sites that are more reactive than those to be condensed introduce (protection)-(protective group removal) operations. 

The previously unreported 1,2,3-thiadiazole-4-thiolate (33) was synthesized by an extension of Hurd and Mori s cyclization procedure <88JHC1873> in which methyl dithiopropionate was converted to intermediate (32). This was cyclized with thionyl chloride to the 1,2,3-thiadiazole and the protecting group removed to give thiolate (33) (Scheme 10). 

A pentopyranoside-fused butenolide is the key intermediate for the synthesis of the natural micotoxin patulin [226, 227]. Its synthesis involves Wittig olefination of a 3,4-di-O-protected arabinopyran-2-uloside, followed by protecting group removal and dehydration (Scheme 47). In other research, the glucopyranosid-2-uloside 190 was converted into the butenolide derivative 191 by aldol condensation with diethyl malonate and transesterification [228]. The latter was shown to be prone to autoxi-dation, leading to 192. Subsequent Michael addition with hydroxide ion, followed by decarboxylation, furnishes C-branched-chain sugar 193. 

Benzyl -o-xylopyranoside was converted into the alcohol 54 (a somewhat capricious isopropylidenation) [39] and a Mitsunobu inversion with N-hydroxyphthalimide, followed by protecting group removal, gave the hydro-xylamine 55. Transfer-hydrogenation (ammonium formate and palladium-on-charcoal in refluxing methanol) [40] then gave, on a small scale and in almost a quantitative yield, the enantiomer of the desired tetrahydro-l,2-oxazine 52. We have never been able to repeat this result since Figure 4 shows the NMR spectra acquired at the time [41]. 

To overcome the chain fragmentation of sensitive peptides that contain /V-alkyl amino acids caused by acids as described vide supra, the following measures are recommended (1) in solution synthesis the exploitation of protecting groups removed by acids should be minimized (e.g., apply Fmoc chemistry, use acid-labile side-chain protection as little as possible) (2) if the peptides must be subjected to acid use low temperatures (—20 °C) for the shortest time possible (monitor the reaction by HPLC ) (3) in SPPS if the peptide does not contain functionalized side chains, prepare the peptide by Fmoc chemistry on Trt resin and remove the peptide from the resin with HFIP (see Section 10.1.1.2.2). If the peptides have functionalized side chains see point (1). 

These reactions only operate on very sensitive substrates, and protecting groups removable under basic conditions normally resist a Swern oxidation. 

Donepezil was prepared through three steps the first one is coupling reaction in which compound of formula 1 is reacted with a compound of formula 2. The reaction can be carried out at 30-70 °C in the presence of suitable base such as potassium carbonate in the presence of dimethylformamide (DMF). The second step is protecting group removal. The third step is substitution of nitrogen atom, and the last step is hydrolysis and decrboxylation [12,13] as in Scheme 3.1. 

Upon [2 + 2]-photocycloaddition to product E and protecting group removal, the retro-aldol fragmentation can be initiated by base or acid treatment (Scheme 6.18). Under basic conditions, alkoxide F generates an enolate which is subsequently protonated to the 1,5-diketone G. 

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