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.)... 

It should be emphasized that benzyloxycarbonylimidazolium salts are effective agents for the direct mono-iV-protection of deoxynucleosides as their benzyloxycarbonyl derivatives. No over-acylation occurs. However, bis(ter/-butyldimethylsilyl)-deoxy-guanosine failed to react with this reagent.[189]... 

Scheme 2 illustrates a synthesis of the benzyloxycarbonyl derivative (H) of the ester (9a) using chemistry analogous to that for anisomycin (Scheme 1). In the formation of the D-allo-triol (.12),...

The final step, incorporation of ALmethyl-D-leutine, can be carried out as follows. D-Leucine was protected as its benzyloxycarbonyl derivative, and methylation was carried out by the phase-transfer method described above for tyrosine. BOP-promoted coupling between Z,Me-D-Leu-OH and the macrocycle, followed by deprotection, gives didemnin A (60). 

Functional group protection. The NH— group in proline is protected by acylation in the usual Schotten-Baumann manner with benzyl chloroformate to yield the benzyloxycarbonyl derivative (42). Correspondingly the —C02H group in glycine is protected by esterification in ethanol to form the ethyl ester, obtained as the hydrochloride (43) under Fischer-Speier conditions. 

Intramolecular cascade cyclization of compounds 481 in the presence of catalytic amount of HgCl2 gave l,2,3,4-tetrahydro-6H-pyrido[l,2-a]pyr-azin-6-ones 483 (09TL4050). NMR investigations indicated that the reaction goes through intermediate 482, which then cyclized to 483. In the absence of catalyst, the cyclization was found to be sluggish. When instead of (2-N02-Ph)S02 derivative N-benzyloxycarbonyl derivative was used, no cyclized product was obtained. Similar reaction of compound 484 provided a mixture of tricyclic compounds 485 and 486. 

Protect the amino group of alanine as its benzyloxycarbonyl derivative. 

Treatment of benzyl 2-(A-benzyloxycarbonyl)amino-2-deoxy-a-D-gluco-pyranoside with oxygen in the presence of platinum oxide catalyst causes oxidation at C6 hydrogenolysis of the substituents yields 2-amino-2-deoxy-D-glucuronic acid.64 Under similar conditions of oxidation, the A-acetyl derivative is less stable than the A-benzyloxycarbonyl derivative, and complete degradation of the molecule occurs. Glycosides of 2-amino-2-de-oxy-D-glucuronic acid are remarkably resistant to acidic hydrolysis, and the free acid itself is much more stable toward mineral acids than are other uronic acids. 

However, most nucleophiles attack 5-oxazolones at the carbonyl group and the products are derivatives of a-amino acids formed by acyl-oxygen fission. Thus the action of alcohols, thiols, ammonia and amines leads, respectively, to esters, thioesters and amides orthophosphate anion gives acyl phosphates (Scheme 18). The use of a-amino acids in this reaction results in the establishment of a peptide link. Cysteine is acylated at the nitrogen atom in preference to the sulfur atom. Enzymes, e.g. a-chymotrypsin and papain, also readily combine with both saturated and unsaturated azlactones. A useful reagent for the introduction of an a-methylalanine residue is compound (202). Both the trifluoroacetamido and ester groups in the product are hydrolyzed by alkali to give a dipeptide. The alkaline hydrolyzate may be converted into the benzyloxycarbonyl derivative, which forms a new oxazolone on dehydration. Reaction with an ester of an amino acid then yields a protected tripeptide (equation 45). 

The amino group of the A-benzyloxycarbonyl derivative is protected as the amide half of a carbamate ester (a urethane, Section 21-16), which is more easily hydrolyzed than most other amides. In addition, the ester half of this urethane is a benzyl ester that undergoes hydrogenolysis. Catalytic hydrogenolysis of the A-benzyloxy carbonyl amino acid gives an unstable carbamic acid that quickly decarboxylates to give the deprotected amino acid. 

Other reactions conducted in pyridine solution include the esterification of simple sugars by N-benzyloxycarbonyl derivatives of amino acids in the presence of N,N - dicyclohexylcarbodiimide339 to produce essentially the 6-O-aminoacyl derivatives, and formation of carbo-... 

One of the syntheses mentioned there started with 3-pyrazolidinone 236, which was protected as the benzyloxycarbonyl derivative 237 in order to obtain selective N-alkylation at position 8 yielding compound 238 after removal of the protecting group. Addition of the resulting amine 238 to l-octyne-3-one 239 formed the enone 240 with the complete diazaprostanoid skeleton. Katalytic... 

Derivatives of threonine have also been used as chiral building blocks in natural product synthesis, For example, a synthesis of the rare monosaccharide Callipel-lose [Scheme 3.125] began with the N-benzyloxycarbonyl derivative of D-threo-nine methyl ester (125.1).243 Simultaneous protection of the amino and hydroxyl... 

The utility of thiol esters and carbonates as protecting groups is limited by their vulnerability to hydrolysis, The poor overlap between the non-bonded electrons on the sulfur atom (3p) and the n-system of the carbonyl (2p) precludes or diminishes resonance stabilisation of the type enjoyed by normal esters thereby raising their ground state energy, The carbonyl group of the thioester is more electrophilic than a normal ester and hence more reactive. Thiocarbonate derivatives are marginally more stable. The 5-benzoyl derivative of cysteine is 95% hydrolysed in 30 minutes with 2 M ammonia whereas the 5-benzyloxycarbonyl derivative is only 20% hydrolysed in 30 minutes under the same conditions.54... 

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