Amino compounds, acylation

Kim MG, Lee SB (1996) Penicillin acylase-catalyzed synthesis of P-lactam antibiotics in water-methanol mixtures effect of cosolvent content and chemical nature of substrate on reaction rates and yields. J Mol Catal B Enzym 1 201-211 Kohsaka M, Domain AL (1976) Conversion of penicDlin N to cephalosporin(s) by ceU-free extracts of Cephalosporium acremonium. Biochem Biophys Res Commun 70(2) 465-473 Koreishi M, Tani K, Ise Y et al. (2007) Enzymatic synthesis of P-lactam antibiotics and /V-fatty-acylated amino compounds by the acyl transfer reaction catalyzed by peniciUin V acylase from Streptomyces mobaraensis. Biosci Biotechnol Biochem 71(6) 1582-1586 Kupka JY, Shen, YQ, Wolfe S et al. (1983) Partial purification and properties of the alpha-ketoglutarate-linked ring expansion enzyme of beta-lactam biosynthesis of Cephalosporium acremonium. FEMS Microbiol Lett 16 1-6... 

As would be anticipated, amino groups in the homocyclic ring of 1,2-benzisoxazoles behave as normal aromatic amines, forming mono- and bis-acyl derivatives, etc. (67AHC(8)277,p. 296). In th e isomeric 2,1-benzisoxazoles the 3-amino compound exists as such and not in the tautomeric 3-imino form (65CB1562). Amino groups in 3-phenyl substituents behave as normal aromatic amines (67AHC(8)277,p. 331). 

Under the Ritter reaction conditions above described, the sesquiterpene (—)-cariophyllene oxide undergoes an interesting rearrangement, originating an A-acyl amino clovane-type compound, in 33% yield, after purification by flash chromatography (Scheme 21) [92]. 

Numerous examples of the preparation of tetramic acids from N-acylated amino acid esters by a Dieckmann-type cyclocondensation have been reported (Entries 7-9, Table 15.4). Deprotonated 1,3-dicarbonyl compounds and unactivated amide enolates can be used as carbon nucleophiles. In most of these examples, the ester that acts as electrophile also links the substrate to the support, so that cyclization and cleavage from the support occur simultaneously. The preparation of five-membered cyclic imi-des is discussed in Section 13.8. 

The last-mentioned application was the aim of a patent206 dating from 1971. 4,8-Diamino-2,6-dioxabicyclo[3.3.0]octanes, endo-endo as well as endo-exo isomers, were used as starting materials for polyamides. First, the diamines 129 were transformed into their salts with various dicarboxylic acids, and these were polymerized to compounds 130 containing acylated amino moieties as monomeric building blocks (see Scheme 30). 

Thiatriazole-5-thiol 4b was described as being in equilibrium with the thione tautomer 4a (Scheme 2). The thione tautomer is predominant in acetone solution, as is apparent from the 13C NMR spectmm <1977JHC1417>. However, methylation and acylation under basic conditions occur at the sulfur atom. The analogous amino compounds do not occur as the imine tautomers. More data can be found in the earlier reviews <1964AHC263, 1976AHC145>. 

Using similar chemistry l,3-diaryl-2-thiobarbituric acid is acylated with chloroacetyl chloride in the presence of triethylamine. Subsequent (9-alkylation under the mildly basic conditions of sodium acetate yields the 5-oxo derivative <91H(32)907>. It is not necessary to use barbituric acid derivatives to accomplish synthesis of furopyrimidines. Other 6-oxopyrimidines serve well in developing analogues. For example, in a reaction similar to that described above, the acylated pyrimidine (215) undergoes cyclization to a 4-(substituted)amino compound (216) (Equation (74)) <92MI 707-03). 

Reactions of A/-amino compounds with electrophiles. Af-Aminopyridinium cations can be acylated or sulfonylated (with acid halides) and nitrated (H2SO4-HNO3) to give the corresponding N-(substituted amino)pyridines, often isolated as the imides (1014 R = COR, S02R, or N02). 

The 3-amino derivatives have been converted into alky], acyl, and benzylidene derivatives.327 332 Sulfonamides have been prepared,100,328 320 and further reactions (alkylation and acylation328 and condensation with a-naphthoquinones333) performed upon these. The 3-amino compound is converted by hydrazine into tetrahydro-indazolinone (190).334... 

C-Alkylation of the sodio derivative is accomplished by a technique similar to the alkylation of malonic ester. Primary halogen compounds, quaternary ammonium salts,and an alkene oxide have been used as alkylating agents. Alkylation by secondary halides has been less successful. Hydrolysis of the substituted esters to acetylated amino acids is described for leucine (64%) and phenylalanine (83%). Hydrolysis with deacylation has been used to prepare histidine (45%) and phenylalanine (67%). Glutamic acid (75%) is obtained from substituted acylaminomalonates prepared by the Michael condensation of methyl acrylate and the acylated amino esters. ... 

A second approach has been to acylate amino groups in the aminoglycoside molecule. The acylation of kanamycin with L(-)-4-amino-2-hydrox ybutyric acid has led to the synthesis of BB-K8 [222]. This compound, which is extremely active, fails to act as a substrate for any of the aminoglycoside inactivating enzymes produced by Ps. aeruginosa. However, it has recently been shown that BB-K8 is acetylated by a strain of E. coli [111]. 

As an amino compound urea acts with acetyl chloride or acetic anhydride or other acyl-chlorides or anhydrides forming acyl derivatives analogous to acetamide. These compounds are termed ureids. 

The reaction sequence of Scheme 3 might well be classified as an imidazole synthesis from other heterocycles, but it seems more logical to treat this as a cyclization involving formation of the 1,5-bond. The enaminoketone condensation products (12) of 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl compounds are cyclized by base to imidazoles (13) in 60-80% yields." Such a reaction makes use of the well-established general attack of a nucleophilic center in the side chain on N-2 of the oxadiazole ring. Benzamidine combines with 2-amino-3-phenacyl-l,3,4-oxadiazolium bromides to produce 1-acyl-amino-2-benzimidoylamino-4-arylimidazoles. ... 

In combinatorial chemistry, the development of multicomponent reactions leading to product formation is an attractive strategy because relatively complex molecules can be assembled with fewer steps and in shorter periods. For example, the Ugi multicomponent reaction involving the combination of an isocyanide, an aldehyde, an amine, and a carboxylic acid results in the synthesis of a-acyl amino amide derivatives [32]. The scope of this reaction has been explored in solid-phase synthesis and it allows the generation of a large number of compounds with relative ease. This reaction has been employed in the synthesis of a library of C-glycoside conjugated amino amides [33]. Scheme 14.14 shows that, on reaction with carboxylic acids 38, isocyanides 39, and Rink amide resin derivatized with different amino acids 40, the C-fucose aldehyde 37 results in the library synthesis of C-linked fucosyl amino acids 41 as potential mimics of sialyl Lewis. ... 

VIII. Amides, Carbamates, Lactams, A-Acylated Amino Acids or Esters, and Related Compounds... 

---