Synthesis of (±)-biotin from a substituted 2,3-dehydrothiophane

(±)-Biotin has been synthesized from a mixture of cis- and allo-trisubstituted dehydrothiophanes by a scheme providing for the easy elimination of the accompanying allo-substituted thiophane in the form of an intermediate and not as the final isomeric allo-biotin. The imidazoline ring of biotin is formed from a dialkoxy-carbonyldiaminothiophane under the conditions of partial hydrolysis of one of the protective groups with the elimination of phosgene from the scheme of synthesis.All-Union Scientific-Research Vitamin Institute, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 220–223, March–April, 1981.     

Study of the inversion of 4-benzamido-3-hydroxythiophane

Inversion during the acid hydrolysis of trans-4-benzamido-3-hydroxythiophane is accomplished through the intermediate formation of cis-2-phenyltetrahydrothieno[3,4-d]oxazoline. The latter has cis ring fusion, and the oxazoline ring is planar. Opening of the oxazoline ring is not accompanied by inversion and leads to cis-3,4-substituted thiophanes. Migration of the acyl group from the nitrogen to the oxygen atom was detected in substituted thiophanes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.10, pp. 1339–1344, October, 1971.     

Synthetic studies in the field of the curare alkaloids

By oxidation and the identification of the oxidation products, it has been shown that the -[4-(2-alkoxy-5-alkoxycarbonylmethylphenoxy)-3-methoxyphenyl] ethylamides of 4-benzyloxyphenylacetic acid obtained previously and differing in their physicochemical properties are based on the same skeleton and differ only in their spatial configuration, since on Bischler-Napieralski cyclization they give isomeric dihydroisoquinoline compounds. The structure of the latter was established by oxidation to the isomeric acids 2,2-dimethoxy-3,4,5-tricarboxy(diphenyl ether) and 2,2-dimethoxy-4,5,5-tricarboxy-(diphenyl ether); the latter is identical with the compound obtained by the degradation of the methyl ester of natural tubocurarine. 1-(4Benzyloxybenzyl)-6-methoxy-7-(2-methoxy-5-methoxycarbonyl methylphenoxy)-N-methyl-1,2,3,4-tetrahydroisoquinoline and a compound isomeric with it have also been synthesized, and the former has been shown to be identical with a substance obtained by independent synthesis from the 4-benzyl ether of N-methylcoclaurine. During the synthesis of the latter it was shown that cyclization takes place unambiguously without the formation of isomeric compounds.For part XIII, see [2].     

Synthesis of oxazolidine analogs of biotin and epibiotin

dl-cis- and dl-trans-6-(4-Carboxybutyl)-2-oxo-cis-hexahydrothieno[3,4-d]oxazoles were synthesized by the action of phosgene on r-4-amino-c-3-hydroxy-c(or, respectively, )-2-(4-carboxybutyl)thiophan hydrohalides. It is shown that the acid hydrolysis of r-4-benzamido-t-3-hydroxy-c(or t)-2-(4-methoxycarbonylbutyl)thiophans is accompanied by inversion to give r-4-amino-c-3-hydroxy-c(or t)-2-(4-alkoxycarbonylbutyl)thiophans.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 459–465, April, 1976.     

Establishment of the configuration of 4-benzamido-3-oxo-2-(α-hydroxyamino-δ-carbomethoxybutyl)-thiophane

Proton magnetic resonance spectroscopy was used to establish that the addition of hydroxylamine to the exocyclic double bond of 4-benzamido-3-oxo-2-(-carbomethoxybutylidene)-thiophane occurs stereospecifically; the compound formed has the trans configuration with respect to the substituents in the 2 and 4 positions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1600–1601, December, 1972.     

Stereospecific synthesis of all of the possible isomers of 4-ureido-3-hydroxy-2-(5′-alkoxycarbonylbutyl)thiophan

All four possible isomers of 4-ureido-3-hydroxy-2-(5-alkoxycarbonylbutyl)-thiophan were synthesized by the action of potassium isocyanate on the corresponding hydrochlorides (or hydrobromides) of the stereoisomers of A-amino-3-hydroxy-2[5-methoxy (or ethoxy)carbonylbutyl]thiophans, which were obtained by several methods. The configurations of the compounds obtained were proved by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 616–620, May, 1980     

13C NMR spectra and three-dimensional structures of isomeric 3,4-substituted thiophans

The chemical shifts and the direct carbon-proton spin-spin coupling constants for a number of cis and trans isomers of 4-amino-substituted 3-hydroxy(acyloxy)-thiophans, the configurations of the substituents in which and the conformational states were previously established by an independent method, were studied. It was found that in the spectra of the cis isomers the signals of the vicinal ¹³C atoms, which bear the substituents, are shifted to strong field as compared with the trans isomers ( trans-cis 1.7–4.3 ppm). Conformational effects of the substituents on the chemical shifts of the ring ¹³C atoms were noted. It is shown that a relationship exists between the direct carbon-proton spin-spin coupling constants and the spatial orientations of the acyloxy and acylamino substituents for five-membered saturated rings.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1612–1616, December, 1981.     

Stereospecific synthesis of cis- and trans-4-amino-3-hydroxythiophanes

The reduction of 4-benzoylamino- and 4-carbethoxyamino-3-ketothiophanes proceeds stereospecifically to form only trans-4-benzoylamino- and trans-4-carbethoxyamino-3-hydroxythiophanes, respectively, from which trans-4-amino-3-hydroxythiophane is obtained by alkaline hydrolysis. It was established that acid hydrolysis of trans-4-carbethoxyamino-3-hydroxythiophane leads only to trans-4-amino-3-hydroxythiophane, while acid hydrolysis of trans-4-benzoylamino-3-hydroxythiophane is accompanied by inversion to form cis-4-amino-3-hydroxythiophane. Derivatives of the cis- and trans-isomeric pairs of 4-amino-3-hydroxythiophanes were synthesized.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 12, pp. 1609–1613, December, 1970.