Cbz-protected amine

As Boc was chosen as the first protecting group, a Cbz protected amine was introduced. This difference in protecting groups allowed them to be differentiated, which was crucial in the synthesis of (+)-astrophylline. 

Cbz-protected amines behave like amides—they are no longer nucleophilic, because the nitrogen s lone pair is tied up in conjugation with the carbonyl group. They are resistant to both aqueous acid and aqueous base, but they have, to use the analogy we developed in the last chapter, an Achilles heel or safety catch—the benzyl ester. The same conditions that removed benzyl ethers in Chapter 24 will remove Cbz HBr or hydrogenolysis. cleavage of Cbz (Z) in HBr/AcOH... 

The total synthesis of balanol, a fungal metabolite was accomplished by K.C. Nicolaou et al. For the construction of the central hexahydroazepine ring, they have utilized a 7-exo-tet cyclization. The substitution reaction between the mesylate of the primary alcohol and the Cbz-protected amine was effected by a slight excess of base to produce the desired 7-membered ring in high yield. 

Nitrenes, like carbenes, are immensely reactive and electrophilic, and the same Wolff-style migration (insertion into an adjacent C—C bond) takes place in which the substituent R migrates from carbon to the electron-deficient nitrogen atom of the nitrene. The product is an isocyanate. Isocyanates are unstable to hydrolysis attack by water on the carbonyl group gives a carbamlc acid, which decomposes to an amine. Alternatively, reaction with an alcohol gives a carbamate. If the alcohol is BnOH, the product is a Cbz-protected amine. 

Cbz-protected amine 40 in 87 % overall yield from 61, and as a single stereoisomer, through the same isomerization pathway presented in the context of Scheme 7. Asymmetric hydrogenation of the lone C—C double bond in this intermediate using the identical asymmetric catalyst system encountered earlier then completed the assembly of 39 in 97 % yield and with 96 % ee. 

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. 

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... 

After epoxidation of the terminal olefin in syn-89 the pyrrolidine 91 was formed by reductive cleavage of the Cbz-protection and concomitant Sn2 cyclization of the free amine to epoxide 90. In five additional steps (+)-preus-sin (2) was synthesized with an overall yield of 19%. After AT-methoxycar-bonylation and oxidation of the alcohol to an aldehyde the alkyl side chain was introduced by a Wittig reaction. 

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. 

Schistosoma japonicum. The carbobenzoxy (CBz) protected template 160 was initially converted to the a, p-dehydrolactone 161 via the phosphate ester, before undergoing cycloaddition to ylide 162, generated in situ by acidic treatment of A(-benzyl-A(-(methoxymethyl)trimethylsilyl amine. The resultant cycloadduct (163) was isolated in 94% yield as a single diastereoisomer. Destructive template removal, by catalytic hydrogenation, released (5)-( )-cucurbitine, after ion-exchange chromatography, as the free amino acid in 90% yield (Scheme 3.46). 

This is a very simple and short method for the deprotection of N-Cbz and N-Bn groups, which is also applicable for N-Cbz protected amino acids and is compatible with Fmoc protecting groups, which remain unaffected under these conditions. Furthermore, the microwave protocol is fully compatible with enantiomerically pure amino acids and peptides, as no racemisation was observed in the resulting free amines. 

Addition of pyruvate to Cbz-protected D-mannosamine 194 under NeuA catalysis has furnished an JV-acyl derivative of neuraminic acid 5 from which internal reductive amination yielded an azasugar which could be further elaborated to 195, an analog of the bicyclic, indolizidine type glycosidase inhibitor castanospermine [91]. 

The first procedure is the selective protection of an amine in the presence of an indole-NH group or an alcohol.14 Indole-NH (pKa = 17) shows a similar acidity to that of alcohols (pKa = 18). In the next step the benzyloxycarbonyl (CBZ) protected compound 26 is treated with di-fcrt-butyldicarbonate (B0C)20 and DMAP to form 27. Tert-butylchloroformate is unstable and therefore cannot be used for the preparation of BOC derivatives. Conversion of 10 with (B0C)20 in the presence of DMAP would lead to the double BOC protected compound 28. 

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