]Hexitol derivatives containing a 1,4-oxathiane ring

doi:10.1016/S0008-6215(00)82435-0

Carbohydrate Research

Volume 27, Issue 1, March 1973, Pages 157-168

https://doi.org/10.1016/S0008-6215(00)82435-0 Get rights and content

Abstract

The synthesis of 2,5-anhydro-3-O-methylsulfonyl-6-thio-1,4-thioanhydro-D-galactitol (4; type A structure) and 2,5-anhydro-3,4-di-O-methylsulfonyl-1,6-thioanhydro-D-glucitol (10, type B structure), starting from 2,5-anhydro-1,6-dibromo-1,6-dideoxy-3,4-di-O-methylsulfonyl-D-glucitol (1) is described. The 4-O-methyl-sulfonyl group of 10 can be displaced by nucleophiles with retention of configuration. In this reaction, a cyclic sulfonium intermediate 21 is involved, which, depending on the nucleophilicity of the anion, leads to different ratios of type A and B compounds. Introduction of a three-membered ring into the 3,4-position of type B compounds yielded tricyclic derivatives of allitol.

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Cited by (11)

Synthesis of 4-cyano- and 4-nitrophenyl 2,5-anhydro-1,6-dithio-α-d-gluco- and -α-L-guloseptanosides carrying different substituents at C-3 and C-4
2000, Carbohydrate Research
Citation Excerpt :
The formation of all these derivatives can be explained via the sulfonium intermediate 5[3]. Attack of the OH− ion at C-4 will lead with retention of configuration to the hydroxymesylate 6 which undergoes a trans elimination of methanesulfonic acid affording the known [3] allo epoxide 7. A similar attack of the MeO− ion at C-4 will result in the methoxymesylate 10, the mesyl group of which will be split off in an E1cB type process [5] via regeneration of the 3-OH group affording 11.
Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-d-glucitol in methanol with sodium hydroxide afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-d-galactitol, 1,6:2,5-dianhydro-4-O-methyl-1-thio-d-glucitol, 1,6:2,5-dianhydro-3-O-methanesulfonyl-1-thio-d-glucitol and 1,6:2,5-dianhydro-4-deoxy-1-thio-d-erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio-d-xylo-hexitol, the absolute configuration of which was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio-d-hexitol derivatives in which the free OH groups were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of 4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-thio-d-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-α-l- (23) and 1-O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-α-d-xylo-hexoseptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-d-lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23 and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as promoter. The oral antithrombotic activity of the obtained α-thioglycosides was determined in rats, using Pescador's model.
Synthesis of 4-substituted phenyl 2,5-anhydro-1,6-dithio-α-D-gluco- and -α-L-guloseptanosides possessing antithrombotic activity
2000, Carbohydrate Research
Two independent approaches were investigated for the synthesis of 3,4-di-O-acetyl-1,6:2,5-dianhydro-1-thio-d-glucitol (18), a key intermediate in the synthesis of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-α-d-glucoseptanose (13), needed as glycosyl donor. In the first approach 1,6-dibromo-1,6-dideoxy-d-mannitol was used as starting material and was converted via 2,5-anhydro-1,6-dibromo-1,6-dideoxy-4-O-methanesulfonyl-3-O-tetrahydropyranyl-d-glucitol into 18. The second approach started from 1,2:5,6-di-O-isopropylidene-d-mannitol and the allyl, 4-methoxybenzyl as well as the methoxyethoxymethyl groups were used, respectively, for the protection of the 3,4-OH groups. The resulting intermediates were converted via their 1,2:5,6-dianhydro derivatives into the corresponding 3,4-O-protected 2,5-anhydro-6-bromo-6-deoxy-d-glucitol derivatives. The 1,6-thioanhydro bridge was introduced into these compounds by exchanging the bromine with thioacetate, activating OH-1 by mesylation and treating these esters with sodium methoxide. Among these approaches, the 4-methoxybenzyl protection proved to be the most suitable for a large scale preparation of 18. Pummerer rearrangement of the sulfoxide, obtained via oxidation of 18 gave a 1:9 mixture of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-α-l-gulo- (12) and -d-glucoseptanose 13. When 12 or 13 were used as donors and trimethylsilyl triflate as promoter for the glycosylation of 4-cyanobenzenethiol, a mixture of 4-cyanophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-α-l-gulo- (58) and -α-d-glucoseptanoside (61) was formed suggesting an isomerisation of the heteroallylic system of the intermediate. A similar mixture of 58 and 61 resulted when 18 was treated with N-chloro succinimide and the mixture of chlorides was used in the presence of zinc oxide for the condensation with 4-cyanobenzenethiol. When 4-nitrobenzenethiol was applied as aglycon and boron trifluoride etherate as promoter, a mixture of 4-nitrophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-α-l-gulo- (60) and -α-d-glucoseptanoside (62) was obtained. Deacetylation of 58, 61 and 62 according to Zemplén afforded 4-cyanophenyl 2,5-anhydro-1,6-dithio-α-l-guloseptanoside (59), 4-cyanophenyl 2,5-anhydro-1,6-dithio-α-d-glucoseptanoside (63) and 4-nitrophenyl 2,5-anhydro-1,6-dithio-α-d-glucoseptanoside (66), respectively. The 4-cyano group of 63 was transformed into the 4-aminothiocarbonyl, and the 4-(methylthio)(imino)methyl derivative and the 4-nitro group of 66 into the acetamido derivative. All of these thioglycosides displayed a stronger oral antithrombotic effect in rats compared with beciparcil, used as reference.
The fate of the methanesulfonyloxy group on reduction with LAH
1999, Tetrahedron
Reduction of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-D-glucitol with LAH afforded the corresponding 3,4-dihydroxy compound in a yield of 51% and six by-products were isolated after acetylation. Three differed from the original molecule only in the substituents, which were AcO at C-3 and H, CH₃S and CH₃SCH₂S at C-4, respectively. The other compounds had a rearranged skeleton and were 1,4:2,5-dianhydro-1-thio-D-galactitol derivatives, containing the AcO group at C-3 and the aforementioned three substituents attached to C-6. A mechanism is suggested for the rearrangement, and for the formation of the substituent including the fate of the methanesulfonyloxy groups on reduction with LAH which is generally applicable to any mesyloxy derivative.
1,6-Anhydro-1(6)-thio-l-iditol and -d-mannitol, and some derivatives thereof
1977, Carbohydrate Research
Starting from 1,2:5,6-dianhydro-3,4-O-isopropylidene-l-iditol (1) and -d-mannitol (6), respectively, the corresponding 1,6-anhydro-1(6)-thio derivatives (2a and 7a) were synthesized. The discrepancy in the yields obtained, as well as the different behavior of their methylated derivatives (2e and 7c) towards acid hydrolysis, could be explained by steric factors. The di-O-mesyl derivatives 3d and 12c were unstable compounds, and showed no ulcerostatic activity, unlike the d-glucitol analog¹.
Acetalation of 1,6-anhydro-1(6)-thio-D-glucitol
1976, Carbohydrate Research
Acetalation of 1,6-anhydro-1(6)-thio-D-glucitol (1a) with acetone, formaldehyde, or benzaldehyde afforded 2,3:4,5-diacetals (2a, 2b, and 2c) whose structure, after desulfurization, was proved by mass spectrometry. Upon partial hydrolysis of 2a, one of the isopropylidene groups was split off, and the other migrated to O-3,O-4 to give 4b. In 4b, in the stable conformation, OH-2 occupies an equatorial position, whereas OH-5 is axially oriented. Accordingly, OH-2 reacts faster than OH-5 on methylation of 4b, giving 4e. Hydrolysis of the isopropylidene group of the 2,5-di-O-methyl derivative 4d and subsequent mesylation afforded the corresponding 3,4-di-O-mesyl compound 1c, which showed significant ulcerostatic activity.
Synthesis of 1,6-thioanhydro-D-glucitol
1976, Carbohydrate Research
Treatment of 2,4-O-benzylidene-1,6-di-O-tosyl-D-glucitol (1) with potassium thiolbenzoate afforded the 6-S-benzoyl compound 2 and its 5-benzoate 4, the structure of which was proved chemically. When 1 was acetylated and then treated with the thiolate, the acetylated 6-S-benzoyl compound 19 was obtained in good yield in addition to some 1,6-di-S-benzoyl derivative 21. Treatment of 19 with acetic anhydride-acetic acid-sulfuric acid afforded 2,3,4,5-tetra-O-acetyl-6-S-acetyl-1-O-tosyl-D-glucitol (26), which was converted by sodium methoxide into a mixture of 1,5-anhydro-6-thio-D-glucitol (28) and 1,6-thioanhydro-D-glucitol (29). These two compounds were isolated as their acetates (30 and 31) by column chromatography, or by converting 28 into its S-trityl derivative (32).

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]Hexitol derivatives containing a 1,4-oxathiane ring

Abstract

Carbohyd. Res.

Carbohyd. Res.

Carbohyd. Res.

J. Org. Chem.