Glucokinase Activators

A short and practical synthesis of glucokinase activator 1 was developed utilizing a convergent strategy involving an SNAr coupling of the activated aryl fluoride 11 with hydroxypyridine 9. 

Specific activation or inhibition Transport of glucose can be increased or decreased by specihc compounds insulin increases the transport whereas phloridzin, a plant glycoside, inhibits glucose transport by muscle. Insulin increases glucokinase activity in liver, whereas a plant sugar, mannoheptulose, inhibits glucokinase activity. Hexokinase is inhibited by its product, glucose 6-phosphate. 

Regulation of glucokinase activity by glucokinase regulatory protein. 

In conclusion, it should be said that the PolyP-metabolizing enzymes in algae have been little studied. An activity, which transferred Pi from PolyP to ADP, was observed in cell-free extracts from Chlorella (Iwamura and Kuwashima, 1964) and Acetabularia (Rubtsov and Kulaev, 1977). Exopolyphosphatase activity was found in Acetabularia (Rubtsov and Kulaev, 1977), while polyphosphate glucokinase activity was not found in algae (Uryson and Kulaev, 1970). 

E Gonzales, A. Fernandez-Vivas, J. M. Arias and E. Montoya (1990). Polyphosphate glucokinase and ATP glucokinase activities in Myxococcus coralloides D. Arch. Microbiol., 154, 438-442. 

S. O. Uryson and I. S. Kulaev (1970). The glucokinase activity of some green and blue-green algae. Biokhimiya (Moscow), 35, 601-603. 

Glucolipsin A (21) is a macrocyclic dilactone natural product that exhibits glucokinase-activating properties. Fiirstner et al. employed an Evans aldol strategy to synthesize the syn -aldol intermediate 2310 (Scheme 2.1j). The aldol reaction of the boron enolate of 14 with 14-methylpentadecanal (22) delivered the yyn-aldol product 23 in essentially diastereomerically pure form (99% de) after purification. Subsequent glycosidation of the alcohol 23 with trichloroacetimidate (24) was facilitated by catalytic amounts of TMSOTf (20 mol %) to afford the key intermediate (25) in moderate yield. 

Patent Tetrazolyl-Phenyl Actamide Glucokinase Activators... 

Borboni P, Magnaterra R, Rabini RA, Staffolani R, Porzio 0, Sesti G, Fusco A, Mazzanti L, Lauro R, and Marlier LN (1996) Effect of biotin on glucokinase activity, mRNA expression and insulin release in cultured beta-cells. Acta Diabetologica 33,154-8. 

Cabrera-Valladares G, German MS, Matschinsky FM, Wang J, and Fernandez-Mejia C (1999) Effect of retinoic acid on glucokinase activity and gene expression and on insulin secretion in primary cultures of pancreatic islets. Endocrinology 140,3091-6. 

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