Abstract:New δ‐(polyfluoroalkyl)‐δ‐hydroxy‐α‐amino acids were synthesized from the corresponding starting 3‐(benzoylamino)‐6‐(polyfluoroalkyl)‐2H‐pyran‐2‐ones. The key step of the synthesis was the hydrogenation of the pyrone ring. Stereoselectivity and yields depended dramatically on the reaction conditions and the nature of the polyfluoroalkyl group. Various conditions were used for the preparation of both mixtures of diastereomers and pure diastereomers of the target amino acids. The obtained δ‐(polyfluoroalkyl)‐δ‐h… Show more
“…A solution of compounds 1 and 2 (32 mg each) in THF was treated with Pd/C (5% mol, 0.045 g) under a N 2 atmosphere for 15 min. The solution was transferred to a 45 mL stainless steel Parr reactor and pressurized with H 2 (200 psi) at room temperature for 24 h . Then, the excess of gas was released.…”
Brevipolides K-O (1-5), five new cytotoxic 6-(6'-cinnamoyloxy-2',5'-epoxy-1'-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC values against six cancer cell lines, 1.7-10 μM), were purified by recycling HPLC from Hyptis brevipes. The structures, containing a distinctive tetrahydrofuran ring, were established by comprehensive quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data. Detailed analysis of the experimental NMR H-H vicinal coupling constants in comparison with the corresponding DFT-calculated values at the B3LYP/DGDZVP level confirmed the absolute configuration of 3 and revealed its conformational preferences, which were further strengthened by NOESY correlations. NMR anisotropy experiments by the application of Mosher's ester methodology and chemical correlations were also used to conclude that this novel brevipolide series (1-5) share the same absolute configuration corresponding to C-6(R), C-1'(S), C-2'(R), C-5'(S), and C-6'(S).
“…A solution of compounds 1 and 2 (32 mg each) in THF was treated with Pd/C (5% mol, 0.045 g) under a N 2 atmosphere for 15 min. The solution was transferred to a 45 mL stainless steel Parr reactor and pressurized with H 2 (200 psi) at room temperature for 24 h . Then, the excess of gas was released.…”
Brevipolides K-O (1-5), five new cytotoxic 6-(6'-cinnamoyloxy-2',5'-epoxy-1'-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC values against six cancer cell lines, 1.7-10 μM), were purified by recycling HPLC from Hyptis brevipes. The structures, containing a distinctive tetrahydrofuran ring, were established by comprehensive quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data. Detailed analysis of the experimental NMR H-H vicinal coupling constants in comparison with the corresponding DFT-calculated values at the B3LYP/DGDZVP level confirmed the absolute configuration of 3 and revealed its conformational preferences, which were further strengthened by NOESY correlations. NMR anisotropy experiments by the application of Mosher's ester methodology and chemical correlations were also used to conclude that this novel brevipolide series (1-5) share the same absolute configuration corresponding to C-6(R), C-1'(S), C-2'(R), C-5'(S), and C-6'(S).
“…A solution of compounds 8 and 9 (15 mg each) in THF was treated with Pd/C (5% mol, 0.045g) under a N 2 atmosphere during 15 min. The solution was transferred to a 45 mL stainless steel Parr reactor and pressurized with H 2 (200 psi) at room temperature during 24 h . Then, the excess of gas was released.…”
The (6'S)-configuration of brevipolides A-J (1-10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher's ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations. The structure of the new brevipolide J (10) was characterized through NMR and MS data as having the same 6-heptyl-5,6-dihydro-2H-pyran-2-one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p-methoxycinnamoyl moiety found in 8 and 9. Conformational analysis of these cytotoxic 6-heptyl-5,6-dihydro-α-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal (1)H-(1)H NMR coupling constants. Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides. Compounds 7-10 exhibited moderate activity (ED(50) 0.3-8.0 μg/mL) against a variety of tumor cell lines.
“…Subsequent exposure to acidic conditions brought about elimination of formic acid, allowing generation of pyrrole 122 in a yield of 63 %. Further catalytic hydrogenation to 123 was achieved through the employment of conditions already reported in the literature [ 107 , 108 ], followed by hydrolysis to acid 124 in the presence of 6 N HCl. Scheme 27 Synthesis of 5-trifluoromethyl proline, Haufe and co-workers [ 106 ].…”
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