The V /K kinetic parameters for glyceryl-ether monooxygenase with 3-1 '-n-alkoxypropane-I,2-diols having alkyl sidechains varying from Cll to C22 (lb-k, 2a and b, and 3d) were determined. Maximum activity was found with the CI6 ethers, dropping almost to zero with ethers that have sidechains shorter than Cl2 and longer than C19. The thioether analogues with C16 and CI8 sidechains were poorer substrates than the respective oxygen ethers by one order of magnitude. The kinetic parameters for 2-1 '-n-hexadecyloxy-(6a) and 2-1 '-n-octadecyloxy-(6d) ethanol revealed that they were also better substrates than the respective thio-ethers by one order of magnitude and with these compounds those with C16 sidechains were better substrates than the C 18 analogues. L2-bis-3-1 '-n-Hexadecyloxypropan-3-01 (3c) and 1,3-bis-3-1'-n-hexadecyloxypropan-3-01 and 2-01 (4a) were inactive but 3-1'-n-hexadecyloxy-2-methoxypropan-I-ol (3b) and 3-1'-n-hexadecyloxy-l-methoxypropan-2-01 (4b) which have one long fatty chain were viable substrates because they possessed a free hydroxy group, but the ethers (6b, c and e), (7c and d) and (5) which do not have a free hydroxy group were inactive. These data, taken with those reported previously, have allowed us to postulate a model for the active site of the alkyl-ether substrates of the monooxygenase and to define the contours of the hydrophobic and hydrophilic pockets.Keywords: Kinetic parameters of Cll to C22 glycerol ethers, Cl6 and CI8 glycerol thioethers. ethylene glycol ethers and thioethers. syntheses. IH NMR, ORD. glyceryl-ether monooxygenase active site modeL alkyl-ether substrate domain.

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The conformation of the side chain of 5,6,7&tetrahydrobiopterint (6) in 0.5 M DC1/D20 is predominantly quasi-equatorial (deduced from 3J (13C4a, 'H 6) 1.1 HZ), and is the same as that of the methyl group in 2-methyl-1,2,3,4-tetrahydroquinoxaline and in 2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one in the same solvent. Because (-)-(2s)-2-methyl-l,2,3,4-tetrahydroquinoxaline (4) and (-)-(6S)-2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one (5) have the same conformation and negative c.d. spectra (O 248 nm and 263 nm respectively) as does the natural 5,6,7,84etrahydrobiopterin (O minimum at 265 nm) in 0.1 M hydrochloric acid, then the absolute conformations of the tetrahydropyrazine rings and the absolute configurations at the chiral centres C2, C 6, and C 6 of compounds (4), (5) and (6) respectively are the same. Hence the absolute configuration at C 6 in natural 5,6,7,84etrahydrobiopterin is R.A convenient synthesis of biopterint on a gram scale is described.