“…NMR data for this compound are not known in the literature and HRMS data could not be obtained which is likely due to the instability of aliphatic aldehydes.Instead, the crude aldehyde mixture was reduced with NaBH 4 (20 mg, 0.53 mmol) in THF at 0°C. The obtained alcohol had the following NMR data where the 1 H NMR values are in accordance with literature data 24. 1 H NMR (400 MHz, CDCl 3 ): δ 7.20 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 3.68 (t, J = 6.4 Hz, 2H), 2.70, (t, J = 7.6 Hz, 2H), 2.29 (s, 3H), 1.92-1.82 (m, 2H), 1.37 (bs, 1H).…”
A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then consumed in the other chamber in either a rhodium-catalysed hydroformylation of olefins or a palladium-catalysed reductive carbonylation of aryl halides. Hexane-1,6-diol was found to be the optimum alcohol for both reactions where moderate to excellent yields were obtained of the product aldehydes. A relatively low pressure of 1.5-2.4 bar was measured in the closed system during the two transformations.
“…NMR data for this compound are not known in the literature and HRMS data could not be obtained which is likely due to the instability of aliphatic aldehydes.Instead, the crude aldehyde mixture was reduced with NaBH 4 (20 mg, 0.53 mmol) in THF at 0°C. The obtained alcohol had the following NMR data where the 1 H NMR values are in accordance with literature data 24. 1 H NMR (400 MHz, CDCl 3 ): δ 7.20 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 3.68 (t, J = 6.4 Hz, 2H), 2.70, (t, J = 7.6 Hz, 2H), 2.29 (s, 3H), 1.92-1.82 (m, 2H), 1.37 (bs, 1H).…”
A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then consumed in the other chamber in either a rhodium-catalysed hydroformylation of olefins or a palladium-catalysed reductive carbonylation of aryl halides. Hexane-1,6-diol was found to be the optimum alcohol for both reactions where moderate to excellent yields were obtained of the product aldehydes. A relatively low pressure of 1.5-2.4 bar was measured in the closed system during the two transformations.
“…Base-catalyzed hydrolysis of 23 generated 2-hydroxyphenyl pentan-5-ol sulfide ( 24 ). Selective acetylation of the phenolic moiety in 24 in the presence of 1-acetyl-1 H -1,2,3-triazolo[4,5- b ]pyridine gave 62 . 4 …”
All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1-14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX-2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
“…When an unsymmetrical diol is used, the situation is even more complicated because two different monoesters are possible. Despite numerous attempts, − improvement of the mono/di acetylation ratios has not been very successful in attemps to selectively monoesterify diols . No method has been reported to selectively form mixed diesters of diols in a single step.…”
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