1-Acylamido derivatives

The reaction of AK6-amino-4-quinazolinyl)aminomethylenemalonate (1460, R = NH2) and acyl chloride in methylene chloride in the presence of pyridine at 0°C afforded the 6-acylamido derivatives (1505) (81EUP30156). When the amine (1460, R = NH2) was repeatedly reacted with acetic anhydride in pyridine, the /V,/V-diacetylamino derivative (1506) was obtained. Treatment of the amine (1460, R = NH2) with pivaloyl chloride in methylene chloride in the presence of pyridine gave the pivaloylamido derivative (1505, R = Me3C—), while in DMF in the presence of pyridine a mixture of the pivaloylamido and 6-formamido derivatives (1505, R = Me3C— and H) was obtained. 

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

Quinolones have been shown to act as gyrase inhibitors, and are clinically used as antibiotics. A series of quinolones has been conjugated to the 5 -end of short ODNs as 5 -acylamido derivatives using S -amino-S -deoxythymidine. The presence of the quinolone at the 5 -terminus was shown to greatly enhance... 

In a study on the fluorination-toxicity relationship, investigators prepared 1-A-acylamido derivatives of kanamycins, including (2R,3R)- and (27 ,35)-4-amino-3-fluoro-2-hydroxybutanoylkanamycins A and B (compounds 262-265 ). The l-N-[(2/ ,3i )-4-amino-3-fluoro-2-hydroxybutanoyl] derivatives 262-264 showed activity similar to that of the related compoimds [amikacin (2), arbekacin (260), and l-N-[(5)-4-amino-2-hydroxybutanoyl]-3 -deoxykanamycin B 261], whereas the (2R,3S)-derivative 265 (compounds 260 65) showed decreased activity relative to 260. In toxicity, these compounds were similar to the parent antibiotics, and fluorination did not show any influence in the toxicity of the antibiotics [137]. 

Note The important difference between the alkylation procedures involving sodium hydride in polar apiotic solvents and those involving alkyl halides and metal salts is that 0-acyl groups are completely replaced by 0-alkyl groups [30], N-Acyl groups survive and N-ulkyl-N-acylamido derivatives are produced. This alkylation can be performed on an extremely small amount of material and, thus, the procedure provides a rapid means for methylation linkage analysis in the polysaccharide [30], lipopolysaccharide [31] and peptide [20, 32] fields. 

From o-Aminothiophenols (Type A, S—C6H4—N -t- C).—o-Aminothiophenols continue to be widely used as starting materials in benzothiazole synthesis. Their interaction with monosaccharides or glucosides yields products of type (1) or (2). N-(Dichloromethylene)sulphonamides or N-aroyl-S-chloro-isothiocarbamoyl chloride furnish 2-acylamido-derivatives (3/ and (4). l,l-Bis(methylthio)-2,2-dicyanoethylene, dimethyl cyanimidodithioate, and 2,2,4,4-tetrarhethylcyclobutane-l,3-dione (i.e. the dimer of dimethylketen) produce benzothiazole derivatives of types (5), (6), and (7), respectively. 

In addition to the cyclization of 2-acylamido groups with C-l, the 2-acylamido group can form an oxazoline with C-3. The 2-methyl-oxazolines, which are readily hydrolyzed, have not been isolated, but their probable presence is indicated by the inversion observed.144 For a 2-benzamido group adjacent to a suitable leaving-group on C-3, the oxazolines formed are quite stable and can be isolated. The reaction has been conducted on pyranoside derivatives, 37,173-175 such as methyl 2-benzamido-4,6-0-benzylidene-2-deoxy-3-0-(methylsul-fonyl)-jQ-D-glucopyranoside (137) to give 138, furanoside deriva-... 

The solvent in which the ammonolysis of acyl derivatives of carbohydrates is conducted has a great influence on the yields of 1,1-bis-(acylamido)-l-deoxyalditols and N-acylaldosylamines. 

As regards the l,l-bis(acylamido)-l-deoxyalditols, the first structural study was that of Fletcher and coworkers,69 who conducted oxidations with lead tetraacetate. These authors postulated an empirical relationship between the position of the oxidation curve in a graph and the number of hydroxyl groups present. They compared the curves afforded by a series of l,l-bis(acetamido)-l-deoxyalditols with those of alditols having the same number of free hydroxyl groups, and observed a close correspondence. At present, periodate oxidation is widely applied to these mono- or di-saccharide derivatives. Under controlled conditions, the methylation technique can also be applied.42... 

Consideration of rotatory powers of l,l-bis(acylamido)-l-deoxy-alditols showed79 certain correlations between optical rotation (d line of sodium) and configuration that can be summarized as follows. (a) When the acyl group is aliphatic (for example, acetyl or propionyl), the alditol will be dextrorotatory in water if the configuration of C-2 is S. (The rule does not apply to peracetylated derivatives.) (b) When the two substituents on C-l are benzamido and the configuration at C-2 is S, a solution of the alditol in pyridine will be levorotatory. Peracetylation does not alter applicability of this rule, (c) The abso-... 

Table I. Optical Yields for the Asymmetric Hydrogenation of a-(Acylamido)cinnamic Acid Derivatives Using Rhodium(I) Complexes Containing (NmenHCeHsJPC C P eHs ...

Dipyrido[l,2-a 2, 3 -(i]pyrimidine-2,5(l//)-diones 477 were prepared when 2-acylamido-4//-pyrido[l,2-a]pyrimidin-4-ones 382 were heated in a mixture of phosphoryl chloride and dimethylformamide (92JHC25). When the reaction period was only 15 minutes, 2-acetamido derivative 382 (R = Me, R1 = H) gave 3-formyl derivative 478 and tricyclic compound 477 (R = Me, R1 = H) in 31% and 53% yields, respectively. 

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