Synthesis of Purine and Pyrimidine Nucleosides of Thiopentoses<sup>1</sup>

Urbas, Branko; Whistler, Roy L.

doi:10.1021/jo01341a039

Cited by 23 publications

(7 citation statements)

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“…Neither 16 nor 18 would support to any degree (at 1-8 mg/kg) morphine dependence in Rhesus monkeys. In fact 18 precipitated (at 1 mg/kg) withdrawal symptoms when substituted for morphine in dependent monkeys.9 This is similar to behavior shown by 2'-hydroxy-2-methyl-6,7-benzomorphan, the second instance of high analgetic activity and no physical dependence capacity for rigid (morphine-like) structures not containing a quaternary carbon.10 Methoxy compound 15 showed codeine-like activity; the 8d-hydroxy analog 17 was marginally active in mice.…”

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confidence: 74%

“…Removal of catalyst and solvent (in vacuo) left a gummy residue which was dissolved in H20, basified with 12 NH4OH, and extracted with Et20. Washing (H20), drying, and evaporation of the Et20 gave 380 mg (83%) of oily 15 which was converted to the oxalate: mp 204-205°; plates from 95% EtOH; NMR (D20) 1.42 (d, J = 7 Hz, Wolff-Kishner reduction of 14 according to Nagata and I taza-ka13 gave, after chromatography (Si02), a 16% yield of 15 oxalate.…”

Section: Methodsmentioning

confidence: 99%

“…Wolff-Kishner reduction of 14 gave (in low yield) 15 which was better prepared by catalytic hydrogenation of 14 (10% Pd/C, HCIO4, HO Ac, 40°, 50 psi) or of the 8-hydroxy derivative 17. Compound 17, designated as the 8/3-OH epimer (Jg,9 -6 Hz), resulted from catalytic (Pd/C, HCIO4, EtOH) or L1AIH4 reduction of 14.…”

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confidence: 99%

“…Compound 17, designated as the 8/3-OH epimer (Jg,9 -6 Hz), resulted from catalytic (Pd/C, HCIO4, EtOH) or L1AIH4 reduction of 14. The final product, 2,9/3dimethyl-2'-hydroxy-6,7-benzomorphan (18), § whose structure and stereochemistry have been assigned from NMR data of 18-HBr and 17-HC1 (in D20) at 100 MHz ( 1.45, 1.33, respectively, d, J = 7 Hz, C-9 Me)6 and by analogy with 16,17 was prepared in good yield from 15 (refluxing 48% HBr) or 17 (refluxing HI-red P).…”

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confidence: 99%

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Synthesis and pharmacology of 5-noralkyl-9.beta.-methyl-6,7-benzomorphans and stereochemistry of some intermediates

Inoue¹,

Oishi²,

El³

1975

J. Med. Chem.

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2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereochemical assignments of 9, 10 (and thus 7 and 8), and 18 follow from analogy and from NMR data of 9, 10, 17, and 18. Compound 18 and the deoxy analog 16 are as potent as morphine and codeine, respectively, as analgetics (mice) and are without physical dependence capacity (monkeys).

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confidence: 74%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Synthesis and pharmacology of 5-noralkyl-9.beta.-methyl-6,7-benzomorphans and stereochemistry of some intermediates

Inoue¹,

Oishi²,

El³

1975

J. Med. Chem.

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“…R. L. Whistler then studied this substance class in detail [2]. Apart from sulfur-containing six-membered rings, sulfur-containing five-membered rings and also the corresponding sulfur-containing nucleosides could be synthesized [6]. The thio compounds did show one peculiarity; the sulfur in the ring could be oxidized to sulfoxides and sulfones.…”

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confidence: 99%

The Early Days of Monosaccharides Containing Nitrogen in the Ring

Paulsen

1998

Iminosugars as Glycosidase Inhibitors

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The history of the first synthesis of monosaccharides with nitrogen in the ring as well as the discovery of their very strong inhibitory effect on glycoside-cleaving glycosidases much later is a fascinating chapter in carbohydrate chemistry [1,2]. Early attempts to replace the oxygen in pyranoses or furanoses by another hetero atom were made with sulfur. In 1961, the laboratories of J. C. Schwarz [3] and L. W. Owen [4] as well as of R. L. Whistler [5] succeeded independently and simultaneously in synthesizing 5-thio-o-xylopyranose, which contains sulfur instead of oxygen in the ring. The chemical properties of these sulfur-containing saccharides were very similar to those of the oxygen analogs. This is not surprising, since sulfur is divalent and, like oxygen, found in the second main group of the periodic table. The sulfur-containing sugars showed mutarotation and could be converted into the corresponding glycosides. R. L. Whistler then studied this substance class in detail [2]. Apart from sulfur-containing six-membered rings, sulfur-containing five-membered rings and also the corresponding sulfur-containing nucleosides could be synthesized [6]. The thio compounds did show one peculiarity; the sulfur in the ring could be oxidized to sulfoxides and sulfones.At that time we were interested in finding out whether the ring oxygen of pyranoses could also be replaced by nitrogen. The reactions in this case were not predictable, because nitrogen is trivalent and also has basic properties. Aldimines were also possible cyclization products. We first synthesized 5,6-diacetamidol,2-0-cyclohexylidene-5,6-dideoxyhexofuranoses of the n-gluco-and L-idoform, since it could be expected that the 5 -aminosugars would give an appropriate ring closure with nitrogen. Deblocking of the compounds under the required acidic conditions yielded, however, the 2-aminomethyl-5-hydroxypyridine in both cases [7]. This result showed that although a saccharide with nitrogen in the ring had apparently been formed as the intermediate product, it had been converted into the pyridine derivative under the acidic conditions with elimination of three water molecules. With this result the race was on to isolate the nitrogen-containing saccharides that had so far only been identified as intermediate products.We were more successful with 5-acetamido-l,2-O-cyclohexylidene-5-deoxy-Dxylofuranose. It could be deblocked under milder acidic conditions and we were able to isolate the crystalline 5-acetamido-5-deoxy-o-xylopypranose in 1962 [8].Jniinosugfirs ns Glycosidase Inhibitors: Nojirimycin and Beyond. Edited by Arnold E. Stiitz

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