Benzyloxycarbonyl group deprotection

Since the use of N,iV-dimethylacetamide and triethylamine improved the rate and extent of cleavage of the JV-benzyloxycarbonyl group in several difficult cases, these additives have been incorporated into the submitters standard procedure and are included in the present procedures. Deprotection with this method has been carried out with as much as 25 g. of the protected peptide. 

Two amino acid stereoisomers protected by benzyloxycarbonyl groups were deprotected in different ways. One isomer was hydrogenolyzed on 5% Pd/C (0.05 mol Pd/mol) in AcOEt-MeOH for 16 hours at ambient pressure and temperature. The other isomer was dissolved in MeOH, and cyclohexene (10 mol/mol) was added under nitrogen followed by 5% Pd/C (0.18 mol Pd/mol). The temperature was immediately raised to reflux, and stirring was continued for 7 minutes (Scheme 4.60).266... 

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 final step in the solution-phase synthesis is to deprotect the N terminus of the completed peptide. The N-terminal amide bond must be cleaved without breaking any of the peptide bonds in the product. Fortunately, the benzyloxycarbonyl group is partly an amide and partly a benzyl ester, and hydrogenolysis of the benzyl ester takes place under mild conditions that do not cleave the peptide bonds. This mild cleavage is the reason for using the benzyloxycarbonyl group (as opposed to some other acyl group) to protect the N terminus. 

Alkylsilanes have been shown to be versatile deprotection reagents for the benzyloxycarbonyl group. This is achieved by treatment with Et3SiH/PdCl2,f or by reaction with tert-butyldimethylsilane/Pd(OAc)2 which allows the corresponding tert-butyldimethylsiloxy-carbonyl-protected amino acids to be isolated.t l... 

Cleavage of A -(benzyloxycarbonyl) groups from methionine has been achieved. Using liquid ammonia solution also allowed deprotection of (S)-benzylcysteine and other methionine-containing peptides. Simultaneous removal of t-butoxycarbonyl protection occurs to advantage when formic acid as donor is used to remove Z-groups. 

Deprotection of O-benzyl and N-BOC groups.2 This combination of a soft nucleophile and a hard electrophile cleaves O-benzyltyrosine without O to C rearrangement, and also cleaves the benzyloxycarbonyl group at 25°. It was used in a synthesis of the pentapeptide Met-enkephalin, Tyr-Gly-Gly-Phe-Met. It was also used for cleavage of BOC groups protecting the NE-amino group of lysine in a synthesis of a snake venom mastoparan.3... 

Benzodiazepine with a particular stereochemistry at C-3 is obtained by deprotecting the side-chain amino group of the diphenyl ketone (52.14) and treating the product with di-isopropylethylamine. A 3-amino-1,4-benzodiazepin-2-one may be synthesized by addition of ammonium acetate either alone [3308] or with [3283] acetic add to the 2-(a-aminoglycinoylamino)diphenyl ketone at 23 C. The protecting benzyloxycarbonyl group can then be removed. 

Alternatively, compound 14 was oxidized with sodium periodate, followed by reduction with sodium borohydride in ethanol to afford 18 (Scheme 3). Hydrolysis of the isopropy-lidene group in 18 with 50% aqueous trifluoroacetic acid followed by hydrogenation of the azide group and then intramolecular reductive amination and protection of the imine group afforded 19. Selective mesylation of the primary hydroxyl group in 19 followed by silylation and subsequent removal of the benzyloxycarbonyl group and then cyclization with sodium acetate afforded 20. Deprotection of 20 led to me50-quinuclidine-3,5-diol (3). 

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