Formylation of primary hydroxyl groups in sugars.

Application of 99% formic acid at 25 degrees formylates primary hydroxyl groups as shown by the easy formation of 6-O-formyl-D-glucopyranose and 6-O-formyl-D-fructofuranose, isolated as their tetra-acetates in yields of 77% and 31%, respectively. Likewise, D-glucitol gave the 2,3,4,5-tetra-O-acetyl-1,6-di-O-formyl derivative (84%) and methyl alpha-D-glucopyranoside gave the 6-formate (74%) characterized as the crystalline triacetate. On storage of the triacetate in methanol at 25 degrees, the formyl group was lost and the 2,3,6-triacetate was formed, whereas the corresponding tribenzoate was deformylated in acidic methanol without migration of the benzoyl groups.

Synthesis of sweet-tasting methylthio derivatives of D-fructose and sucrose.

1,6-Di-S-methyl-1,6-dithio-D-fructofuranose and its bis(S-oxide) and bis(S,S-dioxide) are described. On examination for sweetness, the oxygenated compounds were neutral but the parent compound was 15-20 times sweeter than sucrose, and 1',6'-di-S-methyl-1',6'-dithiosucrose was slightly less sweet than sucrose.

Synthesis of some derivatives of 6-amino-1,5-anhydro-6-deoxy-D-glucitol and 2-amino-1,5-anhydro-2-deoxy-D-glucitol.

6-Amino-1,5-anhydro-6-deoxy-D-glucitol (11) was prepared from 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (1) in six steps. Reduction of 1 with tributyltin hydride, followed by deacetylation, monomolar tosylation, and reacetylation, afforded 2,3,4-tri-O-acetyl-1,5-anhydro-6-O-toluene-p-sulfonyl-D-glucitol (9). Alternatively, tritylation of 1,5-anhydro-D-glucitol, followed by acetylation, detritylation, and tosylation, gave 9.

Synthesis of N-trifluoroacetyl-L-acosamine, N-trifluoroacetyl-L-daunosamine, and their 1-thio analogs.

A simple and efficient route to N-trifluoroacetyl-L-acosamine (13), N-trifluoroacetyl-L-daunosamine (12), and their 1-thio analogues (18 and 20) is described. Stereoselective reduction of oxime 5 with borane, followed by trifluoroacetylation resulted in the arabino methyl glycoside (8), which, on mild acid hydrolysis gave N-trifluoroacetyl-L-acosamine (13) in an overall yield of 33%, based on L-rhamnal (1). Upon oxidation of the C-4 hydroxyl group and stereoselective reduction of the resulting ketone 11, compound 8 of L-arabino configuration was converted into N-trifluoroacetyl-L-daunosamine (12) in a one-flask sequence with an overall yield of 28% calculated for 1.

Synthesis of 3-C-(hydroxymethyl)erythritol and 3-C-methylerythritol.

3-C-(Hydroxymethyl)erythritol was prepared from 3-C-(hydroxymethyl)-2,3-O-isopropylidene-D-erythro-tetrofuranose (4) by hydrolysis followed by reduction, or by reduction followed by hydrolysis. Monotosylation of 4, followed by reduction with lithium aluminum hydride and hydrolysis, afforded 3-C-methylerythritol.

Effect of 5-thio-D-glucose on food and water intakes and on the acquisition and performance of maze tasks in the rat.

A potent inhibitor of D-glucose transport across the membrane, 5-thio-D-glucose (5-TDG) was examined with respect to its effect on runway and maze performance as well as on food and water intakes and body weight. In an initial experiemnt, three groups of Sprague-Dawley rats were matched in terms of their performance to learn a runway taks with Noyes pellets serving as the reinforcement. After extinction, two groups of rats were given 5-TDG in their food for 14 days, in doses of 20 and 100 mg/kg/day, which exerts potent effects on other functions.

Uridine 5'-(5-thio-alpha-D-glucopyranosyl pyrophosphate): chemical synthesis and activation of rat liver glycogen synthetase.

Uridine 5'-(5-thio-alpha-D-glucopyranosyl pyrophosphate), UDPTG, appears to be a potent activator of rat liver glycogen synthetase a even though it is not a substrate. At 1.0 mM, UDPTG causes over 400% activation of glycogen synthetase a activity.

Temporary sterility produced in male mice by 5-thio-D-glucose.

When 5-thio-D-glucose was fed to male mice at daily dose levels greater than 30 mg/kg sperm development was completely inhibited within 3 weeks and remained so without impairment of libido for the experimental period of 7 weeks. Removal of this substance from the diet resulted in a resumption of sperm development and fertility within 5 to 8 weeks. Normal litters were sired by males which had recovered after this treatment.

Synthesis and biological activity of 5-fluoro-4'-thiouridine and some related nucleosides.

The synthesis of a series of 4'-thio-5-halogenopyrimidine nucleosides, including the 5-fluoro, chloro, bromo and iodo derivatives, has been carried out by condensation of the 2,4-bis-O-trimethylsilyl derivatives of the corresponding pyrimidine bases with the protected 4-thio-D-ribofuranosyl chloride. Among these, the alpha and beta anomers of 4'-thio-5-fluorouridine inhibited the growth of leukemia L1210 cells at concentrations of 4 x 10(-7) and 2 x 10(-7) M, respectively, and that of S. faecium at 4 x 10(-9) and 6 x 10(-10) M, respectively.