Synthesis of Coenzyme

Moffatt, J.G. Khorana, H.G. (1961) Nucleoside Polyphosphates. XII. The Total Synthesis of Coenzyme A. Journal of the American Chemical Society, 83, 663-675. 

Substitution products of the carbon-bonded hydrogen were obtained. A synthesis of coenzyme Q, was achieved in this way (example 6, Table IV). The site of attack in quinones is highly specific and corresponds to the noncarbonyl ring site of highest spin density of the quinone radical anion (lOg, 127). 

A. The cell maintains an important pool of purine nucleotides for synthesis of coenzymes and precursors for DNA and RNA and to support reactions that are coupled to ATP hydrolysis. 

SCHEME 63. Synthesis of coenzyme Q (n lO) and menaquinone-3 via Pd- or Ni-catalyzed alkenyl-benzyl coupling with alkenylalanes... 

SCHEME 70. Iterative one-pot homologation of terpenoids containing 1,5-diene units with ( )-and (Z)-l,4-diiodo-2-methyl-l-butenes and its application to the synthesis of coenzyme Qs, famesol, and geranylgeraniols171... 

Methylesculetol-6,7-dinicotinate (32) is useful as an antiinflammatory and vasodilator oflow toxicity (101). The synthesis of asarone [5555-15-1] (2,4,5-trimethoxy-l-propenylbenzene), which is used as a tranquilizer, has been patented (102). It occurs in calamus root, Acorns calamus L.y and is a chemosterilant for insects (103). 6,7-Dihydroxycoumarin-4-methylsulfonic acid and its salts are useful in the treatment of capillary permeability and fragility and for protecting oxidizable metabolites and drugs against biooxidation (104). Certain chromones derived from hydroxyhydroquinone, eg (33), and its salts, esters, and amides are valuable in the prophylactic treatment of asthma (105) (see Antiasthmatic agents). 2-Methoxy-6-multiprenyl-l,4-benzoquinones are intermediates in the microbiological synthesis of coenzyme Q compounds (106). 

Other pyruvate-containing enzymes include aspartate -decarboxylase from Escherichia coli, the enzyme that catalyzes the formation of -alanine for the synthesis of pantothenic acid (Section 12.2.4) proline reductase from Clostridium sticklandiv, phosphatidylserine decarboxylase from E. coli and phenylalanine aminotransferase from Pseudomonas fluorescens. Phospho-pantetheinoyl cysteine decarboxylase, involved in the synthesis of coenzyme A (Section 12.2.1), and S-adenosylmethionine decarboxylase seem to be the only mammalian pyruvoyl enzymes (Snell, 1990). 

The same sequence is applicable to synthesis of coenzyme Q (ubiquinones, involved in respiratory and photosynthetic electron transport). A representative... 

Deazaflavines and pyrido[2,3-d 6,5-d ]dipyrimidines, which possess an ability to oxidize an alcohol, are obtained from 6-chloro-5-formyl-3-methyluracil and anilines or 6-aminopyrimidines [76CC203 78CPB3208 81JA5943 84TL(25) 1741 86JHC241]. This method is applied to the total synthesis of coenzyme factor 420 [90JCS(P1)253] (Scheme 100). 

Steric control of the mechanism has been clearly demonstrated by the reduction of 3-tosyl-1 -cyclohexane derivatives (Scheme 5). This control has been deployed in the synthesis of coenzyme Qio. The wider use of these reductions has been studied and very high stereoselectivity is observed for hydrogenolysis of famesyl derivatives, —Cl, —OPh, —OSiMe2Bu , —SPh, —SOMe, —S02Me and N(=[Pg.961]

Yes, but he wasn t in the Chemistry Department — an absurdity. I knew about Khorana before I knew about UBC. He was a member of the research staff of the British Columbia Research Council. It was a ridiculous situation. Why he was not invited to join the Chemistry Department, I have no idea. He was by far the most distinguished organic chemist in the whole of British Columbia. He was well known for his work on the synthesis of coenzyme A. I myself had started off in organic chemistry. 

Pantothenic acid is required for synthesis of coenzyme A, CoA and is a component of the acyl carrier protein (ACP) domain of fatty acid synthase. 

Application of the Pd-catalyzed alkenyl-allyl coupling to totally regio- and stereo-controlled synthesis of a-farnesene [92] and a recent synthesis of coenzymes Q3 and Q5 via Ni-catalyzed alkenyl-benzyl coupling [103] demonstrate the synthetic utility of this novel allylation and benzylation methodology (Schemes 1-29 and 1-30). 

In a synthesis of coenzyme uridine-diphosphate-glucose (UDPG), Todd and coworkers protected the primary 5-hydroxyl group of uridine (5) by tritylation, benzylated the 2- and 3-hydroxyl groups (6), and removed the trityl group with 80% acetic acid. 

Pantothenic acid is a precursor for the synthesis of coenzyme A (CoA, CoASH) and forms part of the swinging sulfhydryl arm of the fatty acid synthase complex (Chapter 19). Its structure is shown in Figure 38-20. 

Addition reactions. The mixed alane generated in situ from Me3Al and isobutyl-aluminoxane adds to 1-aIkynes to afford 2-methyl-1-alkenylaluminum reagents. This process has been applied to a synthesis of coenzyme Qio- ... 

Chorismic acid is a metabolic intermediate that is the branch point in the synthesis of coenzyme Q and the aromatic amino acids, phenylalanine, tyrosine, and tryptophan (Figure 21.12). 

Chorismate is formed from 5-enoylpyruvylshikimic acid 3-phosphate (Figure 21.13). Conversion of chorismate to p-hydroxybenzoic acid leads to synthesis of coenzyme Q. Conversion of chorismate to anthranilate leads to biosynthesis of tryptophan (Figure 21.14). 

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