Thiosugars. VIII. Preparation of new 4'-thio-L-lyxo pyrimidine nucleoside analogues.

Reaction of 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose with silylated pyrimidine bases and subsequent deprotection with boron tribromide led to 4'-thio-L-lyxo pyrimidine nucleosides. The 5-bromo-6-methyl derivative was prepared from methyl 2,3,5-tri-O-acetyl-4-thio-L-lyxofuranoside. Deacetylation was performed with sodium methoxide. The anomers were separated by HPLC and their configurations assigned by NMR spectroscopy and X-ray structural analyses. The biological activity of the nucleosides was tested.

The structure of McN-5652.

The configuration of the diastereoisomers of 6-(4-methylthiophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline 1 (McN-5652) is determined and unequivocally assigned by NMR spectroscopy (NOE measurements) and an X-ray structural analysis of the trans diastereoisomer. The enantiomers of cis-1 are separated by preparative HPLC on a chiral phase. One of the enantiomers of cis-1 represents the precursor for imaging the serotonin 5-HT transporter with positron emission tomography (PET).

Thiosugars. Part 9: synthesis and biological evaluation of some 4'-thio-L-arabino nucleoside analogues.

1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-arabinofuranose (10) was transformed into the corresponding cytidine derivative 9 and the adenosine derivative 12. Both nucleosides, as well as the previously reported uridine and thymidine analogues 2 and 3, were tested for their in vitro antiviral activity.

The thio-Mitsunobu reaction of D-glucitol, D-mannitol, galactitol and 1-seleno-D-xylitol.

Unprotected D-glucitol is transformed into 5-O-acetyl-1,4-anhydro-6-thio-D-glucitol (3) in one step by use of the thio-Mitsunobu reaction. Rearrangement (acetyl group migration) to form 3-O-acetyl-1,4-anhydro-6-thio-D-glucitol occurs during column chromatography of 3 on silica gel. 2,5-Di-O-acetyl-1,6-dithio-D-mannitol and 1,6-di-S-acetyl-2,5-anhydro-1,6-dithio-D-glucitol (characterized as the corresponding p-nitrobenzoates) are formed from D-mannitol, whereas galactitol yields a mass of unidentified products. 1-Seleno-D-xylitol, produced by reduction of D-xylose with hydrogen selenide, does not undergo a Mitsunobu reaction.

Preparation of methyl 2,3-di-O-mesyl-4,6-thioanhydro-alpha-D-galactopyranoside and methyl 2-O-mesyl-4,6-thioanhydro-alpha-D-gulopyranoside.

Two 2-oxa-7-thiabicyclo[4.2.0]octane derivatives, 4 and 10, with the D-galacto and D-gulo configuration, respectively, were obtained from methyl alpha-D-glucopyranoside. The thietane cyclization involved a thio-Mitsunobu reaction resulting in a 6-thioacetate, which underwent selective base-catalyzed intramolecular nucleophilic substitution at a C-4 mesylate. The structures of 4 and 10 were elucidated by X-ray diffraction analysis.

Preparation of selenoanhydro- and telluroanhydroglycofuranosides and some corresponding nucleosides.

Methyl 2,3-anhydro-alpha-D-ribofuranoside (3a) was transformed into methyl 2-seleno-2,5-anhydro-alpha-D-arabinofuranoside (5a) and methyl 3-seleno-3,5-anhydro-alpha-D-xylofuranoside (6a) in two steps via the reaction of the C-5 mesylate of 3a, methyl 2,3-anhydro-5-O-mesyl-alpha-D-ribofuranoside (4a), with sodium hydrogen selenide. The corresponding beta anomer of 3a yielded methyl 3-seleno-3,5-anhydro-beta-D-xylofuranoside as the main product and only traces of methyl 2-seleno-2,5-anhydro-beta-D-arabinofuranoside. Sodium hydrogen telluride transformed 4a into methyl 2-telluro-2,5-anhydro-alpha-D-arabinofuranoside. Starting from 5a we prepared 1-(2-seleno-2,5-anhydro-alpha-D-arabinofuranosyl)uracil and the analogous thymidine nucleoside. Compound 6a could not be transformed into nucleosides.

Structure of 2',6'-dihydroxy-4,4'-dimethoxychalcone.

1-(2,6-Dihydroxy-4-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-o ne, C17H16O5, Mr = 300.31, orthorhombic, Pbca, a = 27.903 (3), b = 13.958 (2), c = 7.662 (1) A, V = 2984 (1) A3, Z = 8, D chi = 1.337 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.729 mm-1, F(000) = 1264, T = 295 K, R = 0.040 for 1702 observed reflections. Two intramolecular hydrogen bonds are observed. The hydroxyl H atom at O(6A) is hydrogen bonded to the C(9) carbonyl group with short distances O(6A)...O(9) = 2.406 (3) and O(9)...H(6A) = 1.38 (3), O(6A)--H(6A) = 1.09 (3) A, the angle O(6A)--H(6A)...O(9) is 153 (4) degrees. The other hydrogen bond is of the C--H...O type with distances C(8)...O(2A) = 2.778 (4), H(8)...O(2A) = 2.09 (3) A and the angle around H(8) is 124 (2) degrees. Conjugation is observed between the aromatic rings and the central enone system. The molecule is not planar, the angle between the planes of the phenyl rings being 13.1 (4) degrees. Intermolecular O--H...O bonds with distances O(6A)...O(2A) = 2.689 (2), H(2A)...O(6A) = 1.86 (4) A and angle O(2A)--H...O(6A) = 176 (4) degrees form endless chains of molecules along b.

Structure of 6-dodecyl-2-methoxy-1,4-benzoquinone, a new synthetic contact allergen.

C19H30O3, Mr = 306.45, triclinic, P-1, a = 5.453 (1), b = 5.608 (1), c = 30.129 (2) A, alpha = 85.85 (1), beta = 88.66 (1), gamma = 83.02 (1) degree, V = 912.0 (1) A3, Z = 2, Dx = 1.116 Mg m-3, Cu K alpha radiation, lambda = 1.5418 A, mu = 0.548 mm-1, F(000) = 336, T = 296 K, R is 0.040 for 2489 observed unique reflections. The aliphatic side chain is slightly rotated from the quinone ring. The angle between the quinone-ring plane and the mean dodecyl-chain plane is 20.8 (2) degrees. The average Csp3-Csp3 bond lengths and corresponding angles of the side chain are 1.515 (5) A and 113.8 (3) degrees. The average dimensions of the quinone ring are C-C 1.477 (4), C = C 1.337 (4), C = O 1.222 (3) A, C-C-C 118.9 (3), C = C-C 120.6 (3), O = C-C 120.6 (3)degrees. Neighbouring molecules form dimers by C-H...O interactions across centres of symmetry [C(3)...O(3) 3.413 (2) A]. The dimers are linked together via methyl H and carbonyl O along [100] [C(19)...O(3) 3.338 (3) A]; O(3) is a bifurcated acceptor.