Amino carbamoylation

SYNS CYCLOPROPANE, l-(N-AMINO)CARBAMOYL-2-METHYL- HYDRAZINE, N-((2-METHYLCYCLOPROP-YL)CARBONYL)- KETONE, 2-METHYLCYCLOPROP-YL HYDRAZINO USAF A-14980... 

Based on tandem Dimroth-Comforth rearrangements, reaction of 1,2,3-thiadiazole-4-carboxaldehyde 64 with l-amino -carbamoyl-l,2,3-triazole-5-oIate 65 afforded the sodium A[-(4-thiocarbonyl-l,2,3-triazol-l-yl)carbamoyl-1,2,3-triazol-5-olate 68 with moderate overall yield (Scheme 21) [61]. 

R" = -H, 5-0-carbamoyl-2-amino-2-deoxy-L-xylonic acid or the 3-deoxy derivative... 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

The enamino ketone (49) was reported to give no identifiable products on reaction with N,N-dimethyl carbamoyl chloride 63). However, reaction of (49) with N,N-diethyl carbamoyl chloride in refluxing chlorobenzene gave the N-(3-diethyl-amino-5,5-dimethylcyclohex-2-en-1 -ylidene)pyrrolidinium salt, isolated as the perchlorate. The latter must have been formed as outlined in Scheme I, involving initial O carbamoylation followed by an addition-elimination reaction to give 138 cation which can react with diethylamino anion by a further addition-elimination displacement to give the product 46). 

Chemically synthesised D,L-hydantoins prepared from the corresponding aldehydes via die Bucherer Berg reaction are converted by the bacterial cells (Bacillus brevis), containing a D-spedfic hydantoinase, to a mixture of D-N-carbamoyl amino acid and L-hydantoin. The latter compound undergoes rapid and spontaneous racemisation under the conditions of the reaction, therefore, in principle 100% of the hydantoin is converted into the D-N-carbamoyl compound. The D-amino add is obtained after treatment of the D-N-carbamoyl compound with nitrous add. This process is operated on an industrial scale by the Japanese firm Kanegafuchi. 

An even more elegant approach for the production of D-phydroxyphenylglydne on an industrial scale uses foe bacterium. Agrobacterium radiobacter (Figure A8.8). The organism is able to produce both D-hydantoinase and a second enzyme, N-carbamoyl-D-amino acid aminohydrolase, which catalyse the hydrolysis of N-carbamoyl-D-amino add. 

Figure A8.9 Procedure for the preparation of optically active a-disubstituted amino acids through stereoselective enzymatic cydisation of the N-carbamoyl derivatives.

Note The A-substituent may be varied considerably for example, the amino group may be part of a carbamoyl group. 

Note Several complicated but interesting examples of this cyclization have been reported all involve loss of a substituted-amino portion of the carbamoyl grouping. 

Quinoxalinedicarboxylic anhydride (47) and 2-amino-4,5,6,7-tetrahydroben-zo[Z ]thiophene-2-carboxylic acid (48) gave 3-[iV-(3-carboxy-4,5,6,7-tetrahy-drobenzo[/7]thien-2-yl)carbamoyl]-2-quinoxalinecarboxylic acid (49) (EtOH, reflux, 30 min 80% analogs likewise). 

The main application of the enzymatic hydrolysis of the amide bond is the en-antioselective synthesis of amino acids [4,97]. Acylases (EC 3.5.1.n) catalyze the hydrolysis of the N-acyl groups of a broad range of amino acid derivatives. They accept several acyl groups (acetyl, chloroacetyl, formyl, and carbamoyl) but they require a free a-carboxyl group. In general, acylases are selective for i-amino acids, but d-selective acylase have been reported. The kinetic resolution of amino acids by acylase-catalyzed hydrolysis is a well-established process [4]. The in situ racemization of the substrate in the presence of a racemase converts the process into a DKR. Alternatively, the remaining enantiomer of the N-acyl amino acid can be isolated and racemized via the formation of an oxazolone, as shown in Figure 6.34. 

C9H13NO 104-63-2) see Indeloxacine Phenmetrazine 7-(2-benzylaminoethyl)theophylline (C15H19N5O2 22680-61-1) see Fenetylline Theodrenaline benzyl [(2R,35)-3-amino-2-hydroxy-4-phenylbutyl](2-methylpropyl)carbamate monohydrochloride (C22H3[C1N20j 160232-11-1) see Amprenavir 2-benzylamino-l-(4-methoxyphenyl)propane (C17H21NO 43229-65-8) see Fenoterol Formoterol benzyl [3-[(2-aminophenyl)carbamoyl]propyl]methyl> carbamate... 

In many cases, the racemization of a substrate required for DKR is difficult As an example, the production of optically pure cc-amino acids, which are used as intermediates for pharmaceuticals, cosmetics, and as chiral synfhons in organic chemistry [31], may be discussed. One of the important methods of the synthesis of amino acids is the hydrolysis of the appropriate hydantoins. Racemic 5-substituted hydantoins 15 are easily available from aldehydes using a commonly known synthetic procedure (Scheme 5.10) [32]. In the next step, they are enantioselectively hydrolyzed by d- or L-specific hydantoinase and the resulting N-carbamoyl amino acids 16 are hydrolyzed to optically pure a-amino acid 17 by other enzymes, namely, L- or D-specific carbamoylase. This process was introduced in the 1970s for the production of L-amino acids 17 [33]. For many substrates, the racemization process is too slow and in order to increase its rate enzymes called racemases are used. In processes the three enzymes, racemase, hydantoinase, and carbamoylase, can be used simultaneously this enables the production of a-amino acids without isolation of intermediates and increases the yield and productivity. Unfortunately, the commercial application of this process is limited because it is based on L-selective hydantoin-hydrolyzing enzymes [34, 35]. For production of D-amino acid the enzymes of opposite stereoselectivity are required. A recent study indicates that the inversion of enantioselectivity of hydantoinase, the key enzyme in the... 

The leuco quinoneimine dyes are unstable to isolate but the substitution of an electron-withdrawing group such as acyl,13 carbamoyl,13 carboxy,13 or arylsulfonyl 12 group at the amino nitrogen atom stabilizes the... 

Aldehyde semicarbazones with two substituents on the terminal amino group (but not the hydrazino) (33) react with diazonium salts to yield N-carbamoyl-substituted formazans (34) (Eq. 4).47,48 A sulfonic acid deriva-... 

Hypermodified nucleosides that contain an attached amino acid at C(6) are important in the biochemistry of RNAs. The Ni11 complex with N-[(9-/3-D-ribofuranozylpurin-6-yl)-carbamoyl]-threonine (699) forms a very stable complex involving N(l) of the purine ring, the amide-N and the carboxylate of the attached threonine as donors.1837... 

Phenylthio-carbamoylated amino acids RP c8 Phenyl-carbamoylated P-cyclodextrin... 

N-derivatized a-amino acids N-methyl tert-butyl carbamoylated quinine Methanol—O.IM 203 ammonium acetate, pH 6.0 (80 20)... 

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