S-Benzyloxycarbonyl derivatives

When cysteine reacts with an alkyl or aryl chloroformate, both the -SH and -NH groups are protected, as a thiocarbonate and as a carbamate, respectively. Selective or simultaneous removal of the protective groups is possible. (See cleavage conditions 3-6 for an S-benzyloxycarbonyl derivative, page 485.)... 

An efficient method of resolution of diastereomeric mixtures of 5-substituted 2-oxazolidinones, utilizing commercially available (S)-l-phenylethylamine as the optically active portion of the molecule, has been developed16. Thus, the Ar-benzyloxycarbonyl derivative of (S)-TV-(l-phen-ylethyl)-2-propen-1-amine (1), treated with iodine in chloroform, affords the diastereomeric products as a 50 50 mixture which is easily separated by chromatography on silica gel. 

An important application of hydrogenating ester cleavage is involved in Bergmann s benzyloxycarbonyl method of synthesizing peptides.79 In this an amino acid is treated with benzyl chloroformate and then coupled with another amino acid molecule the benzyl group of the resulting benzyl carbamate residue produced is finally removed as toluene, the carbamic acid derivative that results decomposing immediately to carbon dioxide and the desired peptide ... 

V. P. Kumar, M. S. Reddy, M. Narender, K. Surendra, Y. V. D. Nageswar, K. R. Rao, Aqueous phase mono-protection of amines and amino acids as A-benzyloxycarbonyl derivatives in the presence of j8-cyclodextrin. Tetrahedron Lett., 2006, 47, 6393-6396. 

Amino-sugars and Related Compounds. VI. The Action of Alkali on Some Benzyloxycarbonyl-amino Derivatives, A. B. Foster, M. Stacey, and S. V. Vardheim, Acta Chem. Scand., 13 (1959) 281-288. 

During synthetic studies on the antitumour antibiotic CC-1065, ready access was required to a series of 6-substituted indole-3-carboxylates. The following example illustrates the successful general strategy that was developed reaction of the N-Cbz derivative of N-(3-methylphenyl)hydroxylamine with methyl propiolate in nitromethane as solvent and in the presence of Hunig s base gave methyl l-benzyloxycarbonyl-6-methylindole-3-carboxylate directly in 89% yield. 

Asymmetric reduction of imines. Japanese chemists2 have prepared a number of chiral sodium triacyloxyborohydrides from N-acyl derivatives of natural a-amino acids. The most effective are derived from (S)-proline. A particularly useful reducing agent is 1, derived from N-benzyloxycarbonyl-(S)-proline (equation I). 

The hydroboration of ( )-baikiain (4,5-dehydro-( )-pipecolinic acid) via its JV-benzyloxycarbonyl methyl ester derivative (134) led, after oxidation and removal of the protecting groups, to 72% trans-5-hydroxy-( + )-pipecolinic acid (136) and 28% (raw.s-4-hydroxy-( + )-pipecolinic acid (135), separable by preparative ion-exchange column chromatography.118... 

Treatment of the adenine derivative 1.84 with l-(benzyloxycarbonyl)-3-ethylimidazolium tetrafluoroborate (Rapoport s reagent 1.85) forms 1.86 in 82% yield in which the NH2 group is protected with Cbz. 

Further changes in the P1-P5 region, which resulted in improved efficacy for these synthetic substrates, were based on elastin, HLE s natural substrate [36]. This excellent substrate is an insoluble, structural protein, which is primarily composed of hydrophobic amino acid residues. However, it also contains a number of Lys-derived, cross-linked residues, such as desmosine and isodesmosine, that incorporate a positively charged pyridinium ring. In order to model this cross-linking feature, Lys or various amino-protected forms of Lys, were systematically incorporated into the substrate MeO-8uc-Ala-Ala-Pro-Val-NA (4-1). Replacement of any single residue with Lys led to decreased activity, for example, (4-2)-(4-4) Table 2.4). However, the use of side-chain protected Lys derivatives (e.g. the NHj terminus protected with benzyloxycarbonyl or picolinyl) led to increased reactivity to elastase with the optimal position for substitution being P4, see (4-5)-(4-8). 

All diamino alcohols (2a-g) were derived from N-Z-(S)-proline via the intermediate N-[(N-benzyloxycarbonyl)prolyl]proline methyl ester (4). The diamino alcohol 2a WHS obtained by the reduction of 4 with LiAlH, and 2b-e were obtained by the reaction of 4 with the corresponding Grignard reagents. Diamino alcohols 2f-g and triamino alcohol 5 were obtained by the following sequence of reactions ... 

The 3-methyl ethers of the 4,6-0-benzylidene and 4,6-0-ethylidene derivatives of methyl 2-(A-benzyloxycarbonyl)amino-2-deoxy-a-n-gluco-pyranoside have been prepared by a sequence of reactions paralleling Neuberger s synthesis. The d anomer of the latter compound was obtained directly by methylation of 2-(A-benzyloxycarbonyl)amino-2-deoxy-4,6-0-ethylidene-D-glucose with dimethyl sulfate and alkali. Both anomers were transformed into the free amines by catalytic hydrogenolysis. ... 

S)-l-Benzyloxycarbonyl-2-[hydroxy(diphenyl)methyl]pyrrolidine [(S)-25] was used as an auxiliary in the enantioselective reduction of carbonyl compounds to secondary alcohols (Section D.2.3.2.) it is prepared analogously to the a,a-dimethyl derivative25. The A -methyl derivative (S)-26 (DPMPM) is among the most selective catalysts for the addition of zinc alkyls to carbonyl compounds (Section D.1.3.1.4.). 

H. Sano, S. limura, T. Tsuchiya, and S. Umezawa, Reactions of benzyl 2-benzyloxycarbonyl-amino-2-deoxy-3-0-mesyl-a-D-gluco- and -a-D-allopyranoside derivative with iodide. Bull. Chem. Soc. Jpn., 51 (1978) 3661-3662. 

---