Side-Chain, Reduction

Early stmctural determination lends iasight iato the chemical reactivity of vitamin K. Catalytic hydrogenation of vitamin consumes four moles of hydrogen and affords a colorless compound. Because complete hydrogenation of a 1,4-naphthoquiaone stmcture consumes three molecules of hydrogen, consumption of the fourth mole iadicates unsaturation ia the side chain. Reductive acetylation of vitamin affords the diacetate of... 

Oxidative cleavage of the ketonic side chain reduction of the keto group... 

We envisioned that the B ring of cylindrospermopsin (1) could be prepared by an intramolecular SN2 reaction of the guanidine of 4 on the bro-moketone. Equilibration would provide the desired equatorial side chain. Reduction of the ketone, deprotection and sulfation would complete the synthesis of cylindrospermopsin. Addition of acetylene 5 to pyrimidine... 

Even prior to the elucidation of the first committed step of the riboflavin pathway, it had been shown that the benzenoid ring of riboflavin is assembled from two identical 4-carbon precursors. More specifically, the final step in the biosynthesis of the vitamin involves a dismutation of 6,7-dimethyl-8-ribityllumazine (6), where one of the substrate molecules serves as donor and the other as acceptor of a 4-carbon segment.19,20 6,7-Dimethyl-8-ribityllumazine, in turn, is formed in the penultimate step of the biosynthetic pathway from 5-amino-6-ribitylamino-4(3f/)-pyrimidinedione (3), an intermediate that is obtained from the product of GTP cyclohydrolase II by a sequence of deamination, side chain reduction, and dephosphorylation (Figure 3). The nature of the 4-carbon precursor required for the formation of 6,7-dimethyl-8-ribityllumazine (6) from 5-amino-6-ribitylamino-4(3f/)-pyrimidinedione (3) remained controversial for quite a long period, with working hypotheses including, but not limited to, tetroses, pentoses, and acetoin. 

Sodium/ammonia" treatment also causes disruption of the ring in thiophene and simple thiophenes, however thiophene-2-carboxylic acid and 2-acyl-thiophenes can be converted into the 2,5-dihydro derivatives using lithium in ammonia, followed by protonation or trapping with an alkyl halide."" Side-chain reductions can be carried out with metal hydrides, which do not affect the ring. 

A more difficult problem is encountered when it is necessary to reduce selectively multiple bonds in the side chain, especially when they are conjugated with the nucleus. Up to the present time little has been published on this subject. The best method for the side chain reduction of /3-2-furylacrylic acid seems to be with Raney alloy in dilute NaOH. If the reaction is carried out more drastically, the nucleus undergoes easy reduction to give 4-hydroxy-valerolactone. The method of Railings and Smith also appears to be successful this involves the use of palladium strontium carbonate for the reduction of the alkene side chain of 2 -furylalkenes, without affecting the ring. Such compounds as j8-2 -furylacrylic esters are exceptions, but the potassium salt of the acid can be selectively reduced in aqueous solution. 

Protein binding and metabolism In liver by heparinase inactive metabolite is excreted Bound to albumin (99%), side-chain reduction to... 

GVGVP GFGVP GVGVP GVGK[NMeN]P) D-K/IF of Table 5.5, where n is for the aspartic acid residue with the side chain, -CH2-COOH, that accompanies the N-methyl nicotinamide functional group attached to a lysine side chain. Reduction of NMeN to form NMeN shifts the transition zone for protonation of the carboxyl function by 2.5 pH units. This shows electrochemical transduction, the conversion of electrical energy into chemical energy. In particular, the reduction reaction is carried out near pH 9, where the reduced NMeN is most stable. 

The diol XI-80, obtained by the side-chain reduction of the keto ester (XI-79) with sodium borohydride, served as a precursor to 5-methylindolizine (XI-82). However, the yield was low in this synthesis and the indolizine could be prepared by a more favorable route from the aldehyde XI-81. 

Corydamine, C20H18N2O4, incorporates a bis(methylenedioxy)-3-aryl-isoquinoline system with an 7V-methylaminoethyl side chain. Reductive methylation of corydamine led to the tertiary base 5 which was converted by quaternization and Hofmann elimination to the isoquinolinostyrene 6. iV-Methylation of 6 followed by borohydride reduction gave rise to the known anhydroprotopine-B. Alternatively, when the methiodide of 5 was pyrolyzed in dimethylformamide, the protoberberine salt coptisine iodide was obtained. ... 

E) under the influence of dihydrofolate synthase (EC 6.3.2.12). Repetition of the same sequence of phosphorylation and amide formation serves to extend the amide side chain. Reduction (NADPH, dihydrofolate reductase, EC 1.5.1.3) leads to tet-rahydrofolate, which, itself, can undergo changes in the number of glutamate (Glu, E) side chains (tetrahydrofolate synthase, EC 6.3.2.17). 

An ethereal soln. of 5-methyl-3-phenyl-l,2,4-oxadiazole added dropwise to a stirred refluxing soln. of LiAlH4 in the same solvent, stirring and refluxing continued 1 hr. N-ethylbenzamidoxime. Y ca. 100%. F. e., also side chain reductions with NaBH4 without ring opening, s. M. Tavella and G. Strani, Ann. chim. (Rome) 51, 361 (1961). 

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