3-Ethoxycarbonyl / -lactams

First, 4-chloropyrimidine 86 was treated with phenylacetylene to give alkynylpyrimidine 87 [62], The fact that the Sonogashira reaction proceeded readily at room temperature may be ascribed to the electron-withdrawing effect of the neighboring ethoxycarbonyl group on 86. When heated with ammonia in EtOH, alkynylpyrimidine ester 87 cyclized efficiently to produce pyridyl lactam 88. 

Aminal reduction (NaBH3CN, 2 M HC1, EtOH) of the C-5-methoxycarbonyl pyrroloimidazole 52a or its enantiomer 52b resulted solely in lactamization to pyrrolopyrazines 53a and 53b, respectively the C-5-ethoxycarbonyl pyrroloimidazole 52c similarly cyclized to 53c (Equation 5) <1996TL1711, 1997TL1647>. 

Of interest is also that the rate of liberation of penicillin G from the prodrug was much faster than the breakdown of the former by opening of its /3-lactam ring. Furthermore, no breakdown of the pro-moiety A-(hydroxy-methyl)-A-[(ethoxycarbonyl)methyl]benzamide (8.58) to liberate formaldehyde was detected over the timescale of ester hydrolysis. 

Ketene-imine cycloaddition reactions of ethoxycarbonyl(phenylthio)ketene with various imines and subsequent desulfurization reactions have been reported in 2006 to synthesize 3-ethoxycarbonyl (3-lactam derivatives [108]. 

In 2003, Cainelli and coworkers have shown that monocyclic [3-lactams substituted at the C-3, the C-4, and the N-l positions are the most active in inhibiting LE and gelatinases MMP-2 and MMP-9 [340], They have also reported that C-4 unsaturation on the [3-lactam ring raised the inhibitory activity towards these proteases, with selectivity over LE by 3- 1 -(A/V-butyldi methyl si lyloxvjethyl] derivatives, and over the gelatinase MMP-2 by C-3-unsubstituted 4-[l-ethoxycarbonyl]... 

Acylation of l,2,4-triazolo[l,5-c]quinazoIin-5-one (141) with ethyl chlo-roformate occurred at N6 to afford the 6-ethoxycarbonyl derivative 142 (75CB3799) (Scheme 55). This result indicates that the amide tautomer (lactam tautomer) 141 prevailed over the corresponding imidic acid tautomer (lactim tautomer). 

Azetidin (45)-4-Ethoxycarbonyl-2-oxo-1-trimethylsilyl- E16b, 102 (Lactam-Ringschl.)... 

Variations on the same theme were explored in the preparation of polycyclic P-lactams from the Sml2-promoted cyclization of C4-keto-functionaliz-ed l-[(benzoyloxy)(ethoxycarbonyl)methyl]-2-azetidinones (Scheme 11) [13]. Cyclization of the azetidinone 18 afforded stereoselectively the tricyclic [4.5.6] core structure of the potent antibiotic sanfetrinem as the major compound, whereas in many of the other cases tested (e.g., with 19), cyclization... 

Feroci M, Lessard J, Orsini M, Inesi A (2005) Electrogenerated cyanomethyl anion in organic synthesis a simple diastereoselective synthesis of cis-3-alkyl-l-benzyl-4-ethoxycarbonyl-P-lactams. Tetrahedron Lett 46 8517-8519... 

In 2005, a diastereoselective synthesis of c -3-alkyl-l-benzyl-4-ethoxycarbonyl-p-lactams has been reported to be developed by galvanostatic electrolysis of a solution of acetonitrile containing a tetraalkylammonium salt, as supporting electrolyte and Al-(ethoxycarbonyl)methyl-Al-benzyl-2-bromoalkylcarboxamides [165]. The electrogenerated cyanomethyl anion, at room temperature and under a nitrogen atmosphere, caused the cyclization of the substituted carboxamides. High cisitrans ratios were observed with all the substrates exploited, (Scheme 68). 

The lactam function in l-ethoxycarbonyl-4,5-dihydro-l/f-l,4-diazepin-5-one (85) reacts as expected with triethyloxonium fluoroborate to form the fully unsaturated iminoether (11) <90CPB29ii>. The iminoether moiety of 2-methoxy-3-methyl-3/f-diazepine (86) is cleaved to the lactam (87) on reaction with HCl in methanol <87CPBli79>. 

Hydrazinolysis of 4-ethoxycarbonyl-3-methyl-5-benzamidoisothiazole (77) is attended by ring expansion to pyrimidines (these Reports, Vol. 1, p. 374). In contrast, its chlorobenzamido-analogues (78) are converted merely into the hydrazides (79), which are also accessible from the lactams (80). The difference in the course of the reaction must be ascribed to the effect of the halogen substituents. ... 

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