From a Single Pyridine Substrate

Such syntheses may be subdivided according to which bond of the resulting 1,5-naphthyridine is formed in the process. Of the five possibilities, only three are represented in the literature. 

Several preparations within this category are illustrated in the following examples. 

2-Ethoxalylmethyl-6-methoxy-3-nitropyridine (9) underwent reductive cycliza-tion to 3-hydroxy-6-methoxy-3,4-di hydro-1,5-naphthyridin-2(l//)-one (10) (Pt02, H2, 3 atm, EtOH, 20°C, 2 h 69%) that was easily aromatized to give 6-methoxy-1,5-naphthyridine-2,3( 1 //, 5//)-dione (11) [TsCl, pyridine, 150°C ( ), 4h 83%] 234 

Such a synthesis is evident in the Dieckmann cyclization981 of ethyl 3-[2-(ethoxycarbonyl)acetamido]-2-pyridinecarboxylate (15) (prepared in situ) to give 

4-hydroxy-1, 8-naphthyridin-2( 1 //)-one (16) (EtONa, EtOH, reflux, 5h resulting solid, NaOH, H20, reflux until gas-ceased 69%).1023 

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The primary synthesis of 1,6-naphthyridines has been accomplished by condensation of two or more aliphatic substrates by cycbzation of a single pyridine substrate by condensation of a pyridine substrate with an aliphatic synthon that provides one, two, three, or even four ring atoms by condensation of a pyridine substrate with two or more synthons or from other heterocyclic substrates by degradation, rearrangement, or other elaborative processes. 

The kinetic behavior of GMD is quite complex and displays exquisite sensitivity to reaction conditions including the nature of the buffer and even the order of addition of the substrates." In phosphate buffer GMD exhibits Michaelis-Menten kinetic behavior, and the kinetic mechanism is hi uni uni hi ping-pong, with GDP-mannose binding first and GDP-mannuronate dissociating last. There is a single binding site for the pyridine nucleotide cofactor, so after oxidation of GDP-mannose to the aldehyde, NADH dissociates from the enzyme and is replaced by NAD" " so the second oxidative step can take place. 

Some of the enantiopure phospholane oxides 116 were used for further transformations. For example, they could be isomerised by treatment with base for several hours in a protic solvent to afford 117 or subjected to a second deprotonation to produce 118 as a single isomer. Attempts to prepare Z)w(phospholanes) by double nucleophilic attack of the anions derived from 116 were unsuccessful. Some of the phospholane oxides were reduced with tri-chlorosilane/pyridine to afford the free phospholane with retention of configuration. The same strategy was applied to 1-phenylphospholane oxide but low yields of racemic products were obtained. This suggests that substrate 115 is probably a special case due to the formation of a more stable benzylic carbanion. ... 

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