Synthesis and selective molecular recognition of a macrotricyclic receptor having crown ether and cyclophane subunits as binding sites

Abstract

150was added. The aqueous layer was extracted with CH2CI, (3 X 5 mL), and combined CH2C12 layers were washed with 5% aqueous NaHCO, ( I x 10 mL) and H 2 0 (1 X 10 mL), then dried, filtered, and concentrated. Chromatography (9.9:O.l CHCI,/MeOH) afforded 24 (0.019 g, 68%): mp 169-171 OC (EtOAc/ether); IR (CHCI,) ,958,914 cm-I; 'H NMR (60 (s, 6 H), 1.37 (s, 3 H); MS calcd for C14H,,03 (M+-S02Me) 233.1178, found 233.1 155. Procedure for the Conversion of Mercapto Adducts 15 and 20 into Methylthio Adducts 16 and 21, Respectively. Diazabicyclo[5.4.0]undecene (DBU) (1 9 pL, 0.123 mmol) and CH31 (0.1 mL, 1.6 mmol) were added to a solution of the mercapto adduct (0.021 g, 0.0616 mmol) in anhydrous benzene (IO mL). The reaction mixture was stirred for 2 days, then washed with 1 N HCI (3 X IO mL) and H 2 0 ( I X IO mL), dried, filtered, and concentrated to give the corresponding thiomethyl adduct (0.022 g, quantitative yield).Conversion of Amino Adduct 29 into syn-N-Acetylamino Adduct 30. Acetic anhydride (0.5 mL) and pyridine (0.5 mL) were added to a solution of 29 (0.023 g, 0.071 mmol) in CH2C12 (7 mL). The solution was stirred for 23 h, then toluene was added, and the solution was concentrated to give 30 (0.026 g, quantitative yield).Preparation of 0-Acetyl Adduct 28. (Dimethy1amino)pyridine (DMAP) (0.025 g, 0.202 mmol) and acetic anhydride (0.2 mL, 2.0 mmol) were added to a solution of the hydroxy adduct 27 (0.046 g, 0.184 mmol) in anhydrous benzene (8 mL). The solution was refluxed for 3.5 days. Additional 4-(dimethy1amino)pyridine (0.045 g) and acetic anhydride (0.2 mL) were added, and refluxing was continued for 2 more days. TLC showed that the reaction was still incomplete; however, the solution wsa allowed to cool, diluted to 5 mL with EtOAc, washed with 5% (v/v) HCI ( 1 X IO mL) and brine (1 X IO mL), dried, filtered, and concentrated. Chromatography (8:2 petroleum ether/EtOAc) yielded 28 (0.030 g, 52%): mp 136-138 OC (ether); IR (CHCI,)

Structure‐Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A2‐Mediated Arachidonic Acid Release in Intact Platelets

“…While the ethoxy derivative 4 inhibited the arachidonic acid release in the platelets by 56 % at 1 µM, the octyloxy compound 24 still showed 40 % inhibition at this concentration. In the same way, elongation of the conformationally constrained biphenyl carboxylic acid residue of 20 to a terphenyl carboxylic acid (25) did not produce a marked change in potency.…”

“…Preparation started from 6 and ethyl 4-(4-bromomethylphenyl)-benzoate [25] using a procedure similar to that described for the synthesis of 18.Yield: 33 %; mp 230-231°C. 1 (25) …”

Chiral resolution of alcohols by extractive separation of acetals

“…The free carboxylic acids 8-13 were then obtained from the esters by hydrolysis with NaOH in EtOH [9]. Figure 2 and Table 1 show the investigated acetals 16-27 and their corresponding diastereoisomers 16a-27a, which were formed by the reaction of lactols 8-13 with alcohols 14 and 15.…”

Structure—Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A2‐Mediated Arachidonic Acid Release in Intact Platelets.

“…The mixture of 6 (234 mg, 0.63 mmol), t-BuOK (71 mg, 0.63 mmol), and dry DMSO (5 mL) was heated at 110-120°C for 5 min. After addition of ethyl 4-(2-bromomethylphenyl)benzoate [24,25] (200 mg, 0.63 mmol) heating was continued for an additional 15 min at the same temperature.The cooled reaction mixture was diluted with brine and extracted with Et 2 O.The organic layer was dried over Na 2 SO 4 and the solvent was evaporated. The residue was chromatographed with petroleum ether/ethyl acetate (9:1) to yield the diethyl ester of 18 (196 mg, 51 %).…”

“…Preparation started from 6 and ethyl 4-(3-bromomethylphenyl)benzoate [24,25] using a procedure similar to that described for the synthesis of 18. Yield: 45 %; mp.…”