Sulfur Trioxide-pyridine Complex Research Articles

ChemInform Abstract: Preparation of Steroid Hydroxy Sulfates.

AbstractThe steroidal diol monoacetates (I) and (VI) are sulfated with the sulfur trioxide pyridine complex (II) and then deprotected with sodium hydroxide (IV) to yield the sodium hydroxy sulfates (V) and (VII) respectively via the corresponding pyridinium salts, e.g. (III).

Preparation of Steroid Hydroxy Sulfates

Abstract A new synthetic route to steroid hydroxy sulfates has been developed using acetate as a protecting group and pyridine-sulfur trioxide complex as sulfating agent.

Synthesis of 2-hydroxyestriol monoglucuronides and monosulfates

The ring A monoglucuronides and monosulfates of 2-hydroxyestriol were synthesized from 2-hydroxy-estriol 16,17-diacetate by means of the Koenigs-Knorr reaction with methyl α-acetobromoglucuronate and sulfation with sulfur trioxide-pyridine complex, respectively. The conjugated positions of these compounds were definitely established by conversion to 2-hydroxyestriol monomethyl ethers by methylation, then enzymatic hydrolysis. The ring D monoglucuronides and monosulfates of 2-hydroxyestriol were also prepared from 2-hydroxyestriol 2,3-dibenzyl ether by glucuronidation and sulfation in a similar fashion followed by debenzylation, respectively. The positions of conjugation were established on the basis of their 1H-nuclear magnetic resonance spectral data.

Synthesis of the 3-0, 4-0 and 6-0 Sulfates of Methyl 2-amino-2-deoxy-α-D-Glucopyranoside

Abstract Starting with methyl 2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (1), the isomeric methyl 2-amino-2-deoxy-α-D-glucopyranoside 3-, 4-, and 6-sulfates have each been prepared by sulfation of suitably blocked intermediates. Tritylation and acetylation of 1 followed by detritylation gave methyl 3,4-di-0-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (3), having a free 6-hydroxyl group. Base catalyzed 0–4→0–6 acetyl migration provided the corresponding 3,6 di-O-acetyl derivative (4) posessing a free 4-hydroxyl group. Preparation of methyl 4,6-0-benzylidene-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (9) provided the intermediate bearing a free 3-hydroxyl group. 0-sulfation of 3, 4, and 9 was effected with the pyridine sulfur trioxide complex in dry pyridine.

Modified syntheses of dopamine-4-sulfate, epinephrine-3-sulfate, and norepinephrine-3-sulfate: determination of the position of the sulfate group by 1H-NMR spectroscopy.

With respect to the growing interest in sulfoconjugated catecholamines (CAS), reliable syntheses of those substances including high purification and unequivocal identification are required. For the syntheses of the 3-O-sulfates of norepinephrine (NE) and epinephrine (EPI), modifications of the methods of Stolz (12) and Arakawa et al. (1) were performed. Noradrenalone and adrenalone were prepared according to the method of Stolz (12) and sulfated by reaction with pyridine-sulfurtrioxide complex in dry pyridine at 60 degrees C. After reduction of these ketosulfates by sodium borohydride in dry pyridine, NE-3-O-S and EPI-3-O-S were obtained respectively. We synthesized dopamine-4-O-sulfate (DA-4-O-S) by reaction of DA hydrochloride with pyridine-sulfurtrioxide complex in dry dimethylformamide at 20 degrees C (Harbeson et al., 1983). The highly purified products (DA-4-O-S, NE-3-O-S, EPI-3-O-S) were characterized by their melting points (mp), infrared spectra (IR), thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), elemental analysis, and 1H-nuclear magnetic resonance spectroscopy (1H-NMR).

Syntheses of 4-hydroxyestriol monoglucuronides and monosulfates.

The A-ring monoglucuronides and monosulfates of 4-hydroxyesteriol were synthesized from 4-hydroxyestriol 16, 17-diacetate by means of the Koenigs-Knorr reaction with methyl α-acetobromoglucuronate and sulfation with sulfur trioxide-pyridine complex, respectively. The conjugated positions of these compounds were unequivocally elucidated by leading the products to guaiacol estrogens. The D-ring monoglucuronides and monosulfates of 4-hydroxyestriol were also obtained from 4-hydroxyestriol 3, 4-dibenzyl ether by glucuronidation and sulfation followed by hydrogenolysis, respectively. The conjugated positions were established on the basis of spectral data of derivatives. The preparation of 4-hydroxyestradiol 17-conjugates is also described.

Synthesis of a New Anti-Inflammatory Steroidal Acid Ester: Methyl 11β-Hydroxy-3,20-Dioxo-1,4-Pregnadien-21-Oate

The synthesis and anti-inflammatory activity of a new steroidal acid ester, methyl 11β-hydroxy-3,20-1,4-pregnadien-21-oate (5), are described. This compound has been prepared via three different synthetic routes. The first involves oxidation of the benzoate 3 to the aldehyde 4 followed by a Mattox-type rearrangement of the side chain in conjunction with elimination of the benzoyloxy group. The second method, prolonged reaction of 1-dehydrocorticosterone (8) with methanolic cupric acetate, affords methyl ester 5 in low yield. The third approach consists of selective oxidation at C-20 of the methyl 11β,20α and 20β-dihydroxy-3-oxo-1, 4-pregnadien-21-oates (7a and 7b) with sulfur trioxide–pyridine complex. The local anti-inflammatory activities of the new ester 5 and intermediates 3, 4, 7a, and 7b were determined by the cotton-pellet granuloma assay in rats. The anti-inflammatory activity of the title compound is equal to that of the parent steroid, prednisolone. However, unlike the latter compound, the ester does not cause reduction of adrenal and thymus weights or a lowering of plasma corticosterone levels.

Sulfatides of Mycobacterium tuberculosis. Synthesis of the core α,α-trehalose 2-sulfate

α,α-Trehalose 2-sulfate, the core carbohydrate of sulfatides of Mycobacterium tuberculosis, and the 3-sulfate isomer were synthesized by sulfation of 4,6:4′,6′-di- O-benzylidene-α,α-trehalose with pyridine-sulfur trioxide complex to give the 2- and 3-sulfates, which were separated by column chromatography. The ammonium 2-sulfate salt was identical with the natural product obtained from the principal sulfatide (SL-I) of M. tuberculosis.

Synthesis of 3-amino-3-methyl-2-azetidinone-1-sulfonic acid and its derivatives

N-Benzyloxy-2-(N-tert-butoxycarbonyl) amino-2-hydroxymethylpropionamide (8) was synthesized from methyl DL-isocyanopropionate (2). Compound 8 was treated with diethyl azodicarboxylate and triphenylphosphine to give β-lactam derivative (9), which was hydrogenolized with H2/Pd-C to the N-hydroxy compound (10) followed by treatment with TiCl3 to give the unsubstituted β-lactam derivative (11). Sulfonation of 11 with a pyridine-sulfur trioxide complex and deprotection with formic acid afforded a key intermediate, DL-3-amino-3-methyl-2-azetidinone-1-sulfonic acid (12). The desired 3-N-acylamino-3-methyl-2-azetidinone-1-sulfonic acid derivatives (13a, 13c and 13e) were obtained by acylation of 12. None of the compounds (13a, 13c and 13e) showed antibacterial activity, although the 4α-methyl counterparts (13f) had some activities against gram-negative bacteria.

Syntheses of 4-hydroxyestrogen monoglucuronides and monosulfates.

4-Hydroxyestrone 3- and 4-monoglucuronides were synthesized from catechol estrogens by means of the Koenigs-Knorr reaction with methyl α-acetobromoglucuronate. The position of the glucuronyl residue introduced was unequivocally elucidated by leading the products to the known 4-hydroxyestrone monomethyl ethers. Sulfation of 4-hydroxy-estrone with sulfur trioxide-pyridine complex followed by fractional crystallization provided 4-hydroxyestrone 3-sulfate. The isomeric 4-sulfate was prepared from 4-hydroxyestrone 3-benzyl ether by sulfation and subsequent hydrogenolysis. 4-Hydroxyestradiol monoglucuronides and monosulfates were also obtained from the corresponding 17-ketones by borohydride reduction. The preparation of guaiacol estrogen monoglucuronides and monosulfates is also described.

Covalent modification as the cause of the anomalous kinetics of aryl sulfatase A

Mammalian aryl sulfatase A enzymes are known to exhibit an anomalous kinetic behavior in which the enzyme becomes inactivated as it catalyzes the hydrolysis of substrate. Part of the activity of this inactive, turnover-modified form of the enzyme can apparently be restored by the simultaneous presence of substrate and sulfate ion. The present experiments, conducted with 2-hydroxy-5-nitrophenyl [ 35S]sulfate (nitrocatechol sulfate), establish that the turnover-modified enzyme is covalently labeled. The stoichiometry of the incorporation of radioactivity corresponds to 2 g atom of 35S per mole of enzyme monomer (each monomer of rabbit liver aryl sulfatase consists of two equivalent subunits). It is also shown that isolated, turnover-modified enzyme has lost 80% of its secondary structure when compared to the native enzyme. A commonly used sulfating agent, pyridine-sulfur trioxide complex brings about a similar loss of activity and of secondary structure.

Sulfates of the Simple Sugars

This chapter presents the sulfates of simple sugars. In the plant kingdom, sugar sulfates are found combined in many polysaccharides of the algae, although they are rarely found in land plants. In the animal kingdom, these esters occur in mucopolysaccharides, such as heparin, chondroitins, and mucoitin sulfate; they are also found in the cerebron sulfate of the brain. A detailed examination of the molecular structure of a sulfated polysaccharide requires that the positions of attachment of the sulfate groups in the polysaccharide be known and that the chemical reactivity of these groups be understood. Chlorosulfonic acid has certain disadvantages as a sulfating agent; it is unpleasant to handle and generates chloride ions in the reaction mixture, but it is claimed to give mixtures of sulfates less complex than those afforded by the pyridine–sulfur trioxide complex.