Protecting groups Cbz

Nakajima and Okawa prepared cysteine (250 Scheme 3.92) by treating aziridine 127a with dry H2S gas in the presence of a catalytic amount of BF3 Et20 [141]. The resulting thiol 248 was then oxidized with iodine to afford disulfide 249 in 70% overall yield. Removal of the Cbz protecting group afforded cysteine (250). 

S,3R)-Aziridine-2-carboxylic amide 258 (Scheme 3.95) has been used in the synthesis of the cyclic guanidino amino acid, L-epicapreomycidine (260) [145]. Treatment of 258 with saturated ammonia in methanol at 30 °C for 4 days in a pressure bottle resulted in the aziridine ring-opening product, which afforded 259 in 52 % yield after removal of the Cbz protecting group. 

Treatment of intermediate 31 with 2.2 equiv of 4-FB A in EtOH at 72 °C afforded 35 as a white crystalline solid in 90% isolated yield (Scheme 6.9). Hydrogenation in the presence of 5% of Pd/C and 1 equiv of MsOH, efficiently removed the Cbz-protected group. MsOH was used to prevent fluoride reduction resulting in low levels of the des-fluoro by-product. Catalyst filtration, followed by neutralization of the crude reaction mixture with NaOH, afforded free amine 36 as a white crystalline product in 99% isolated yield. Free-amine 36 was isolated as a dihydrate which necessitated drying prior to coupling with oxadiazole chloride 2. 

Carbamates Both O-Bn and N-Cbz protecting groups have been removed by transfer hydrogenolysis (Scheme 4.59). 

Protected pyrazoline derivatives 429 can be transformed by conventional ozonolysis methodology to the corresponding aldehydes 430, then the Cbz protecting group is removed and the intramolecular reductive amination using... 

Another microwave-mediated intramolecular SN2 reaction forms one of the key steps in a recent catalytic asymmetric synthesis of the cinchona alkaloid quinine by Jacobsen and coworkers [209]. The strategy to construct the crucial quinudidine core of the natural product relies on an intramolecular SN2 reaction/epoxide ringopening (Scheme 6.103). After removal of the benzyl carbamate (Cbz) protecting group with diethylaluminum chloride/thioanisole, microwave heating of the acetonitrile solution at 200 °C for 2 min provided a 68% isolated yield of the natural product as the final transformation in a 16-step total synthesis. 

In summary, we have found that allylation of in situ prepared imines proceeds smoothly with allyltrimethylsilane and a catalytic amount of Bi(0Tf)3-4H20. This method offers several advantages including mild reaction conditions, low quantity of the catalyst (1 mol%), and no formation of by-products. Moreover, our protocol does not require prior isolation of the imine. The homoallylic amine is directly obtained as a Cbz-protected group in a one-pot process. 

Boc- and Cbz-protective groups turned out to be not tolerable in this protocol as indicated by epimerization of Boc- or Cbz-protected a-amino aldehydes substrates (e.g., N-Boc-protected 2-amino-3-phenyl-propionaldehyde 70% yield/24h, antijsyn ratio 50 50, 20% ee with 186). 

Benzyl chloroformate. source of the carbobenzyloxy (Cbz-) protecting group. 

In the case of both the Ns protected five- and six-membered heteocycles, the cis-conflgurated precursors were obtained more efficiently than the trans-configurated precursor. However, the introduction of the Cbz protecting group in the trans-derivatives resulted in quantitative conversion to the desired products. 

In the biotransformation process with L-lysine e-aminotransferase in recombinant E. coli cells, a reaction yield of 65-70% mol/mol was obtained for conversion of BMS-201391-01 (Cbz protecting group) to BMS-199541-01 depending upon the reaction conditions used in the process. Similar molar yields were obtained with phenylacetyl- or phenoxyacetyl-protected analogs of BMS-201391-01. Even Na-pro-tected L-Met/L-Homocys-L-Lys dipeptides served as substrates, as did N-e-Cbz- or Boc-protected L-lysines. 

Step 6a Catalytic hydrogenation reduces the vinyl triflate moiety and cleaves the Cbz protecting group. 

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