Synthesis and platelet activating factor (PAF) receptor antagonist activity of 2,5-diarylcylopentanol derivatives

Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine

“…Consistent with hydroboration and oxidations of 1,3-diarylcyclopent-1-enes, the hydroboration and oxidation of 12 preferentially occurs on the face of the olefin opposite to the phenyl group attached to the stereogenic center. 12 This sequence occurs to set a stereochemical triad with both aryl groups trans to the hydroxyl group. The relative stereochemistry of the dihydropyrroloindole core 13 was established by geminal carbon−proton spin-coupling constant ( 2 J C,H ) values (J-based configuration analysis) and the dependence of these values on dihedral angles (see Supporting Information for details).…”

“…Scheme illustrates the strategy we originally envisioned to complete an enantioselective synthesis of 1 . Installation of the stereochemical triad in 1 would be achieved by a sequence of hydroboration and oxidation occurring on the face of the olefin opposite to the aryl group attached to the stereogenic center in 3 . Compound 3 would be synthesized by a sequence of Grignard addition to the chiral dihydropyrroloindolone 4 followed by dehydration of the resulting tertiary alcohol to form the required alkene.…”

“…Dihydropyrroloindole 13 was isolated as a 9:1 mixture of diastereomers in 52% yield over three steps without significant loss of enantioselectivity (96% ee). Consistent with hydroboration and oxidations of 1,3-diarylcyclopent-1-enes, the hydroboration and oxidation of 12 preferentially occurs on the face of the olefin opposite to the phenyl group attached to the stereogenic center . This sequence occurs to set a stereochemical triad with both aryl groups trans to the hydroxyl group.…”

“…The enantiomeric excess was determined by HPLC analysis (220 nm, 25 °C): t R 13.6 min [(1R,3R)]; t R 16.2 min [(1S,3S)], t R 20.5 min [(1S,3R)]; t R 36.3 min [(1R,3S)] [Chiracel AD-H (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexanes/i-PrOH, 93:7, 1.0 mL/min] to be 96% for the (1R,3R)-diastereomer and 97% for the (1S,3R)-diastereomer; [α] D 24 = +78.7 (c 0.25, CHCl 3 ); 1 Synthesis of (1S,2R,3S)-1,3-Diphenyl-2,3-dihydro-1Hpyrrolo[1,2-a]indol-2-ol (13). 12,14 Martin sulfurane 22 (465 mg, 0.691 mmol, 1.50 equiv) was added to the solution of (1S,3R)-1,3diphenyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-ol 11 (150 mg, 0.461 mmol, 1.00 equiv) in CH 2 Cl 2 (5.0 mL) under a nitrogen atmosphere. The reaction was stirred for 30 min at 23 °C.…”