The structure of codonopsinine

A novel transformation of four aldoses to some optically pure pseudohexopyranoses and a pseudopentofuranose, carbocyclic analogs of hexopyranoses and pentofuranose. Synthesis of derivatives of (1S,2S,3R,4S,5S)-, (1S,2S,3R,4R,5S)-, (1R,2R,3R,4R,5S)-, (1S,2S,3R,4S,5R)-2,3,4,5-tetrahydroxy-1-(hydroxymethyl)cyclohexanes and (1S,2S,3S,4S)-2,3,4-trihydroxy-1(hydroxymethyl)cyclopentane

“…To a stirred solution of 55 (142 mg, 0.45 mmol) in methanol (4 mL) was added sodium methoxide (1 M in methanol, 1.3 mL, 1.3 mmol), and the mixture was stirred at 0 °C for 3 h. The solution was neutralized with Amberlite IR 120 (H+), and the resin was removed by filtration to afford 56 (64 mg, 97%) as crystals. 56: mp 103-104 °C; [apD -8.8°( c 0.56, MeOH); NMR (CD3OD) 1.23-1.67 (1 H, m, H-l), 1.70-2.40 (2 H, m, H-5,5'), m,3,4,CH2OH); high-resolution mass spectrum, caled for CgH1304 m/z 149.0812, found + H, 149.0783. Anal.…”

“…13: TLC Rf 0.27 (ethyl acetate/toluene, 1:8); [a]16D +6.3°( c 1.08, CHClg); IR wCHC '3 3000, 2870, 1735, 1450, 1365, 1240, 1085 cm'1; XH NMR 1.60-2.08 (3 H, m, H-1,6,6'), 1.97, 2.01 ( 3X 2, each s, 2 x OCOCHg), 3.26 (1 H, dd, J = 10 and 3.5 Hz, H-3), 3.20-3.47 (1 H, m, H-5), 3.98 (2 H, d, J = 6 Hz, CH2OAc), 4.10 (1 H, t ,J= 3.5 Hz, H-4), 4.42-4.88 (6 H, m, 3 X OCH2C6H5), 5.35 (1 H, t, J = 9 Hz, H-2), 7.20-7.48 (+)-Codonopsinine [(+)-lb], the enantiomer of natural (-)-codonopsinine, and its stereoisomers, (2ñ,3S,4S,5S)-la, Codonopsinine and codonopsine, a new class of the 1,2,3,4,5-pentasubstituted pyrrolidine alkaloids isolated1,2 from Codonopsis clematidea, have been shown to have structures assigned as 1 and 2, respectively, by Russian workers. 3,4 In animal tests the latter has been found to possess hypotensive pharmacological activity with no effect on the central nervous system.5 Shortly after the structure elucidation, in 1972 the Russian group6 reported the relative stereochemistry for these alkaloids to be 2R*,3S*,4S*,5S* as shown in la and 2a, based on analyses of XH NMR coupling constants using the Karplus equation. However, vicinal coupling constants have been shown to be unreliable for assigning configurations of substituted pyrrolidines.7 Thus, it seemed to us that the proposed assignments rested on dubious spectral interpretation, and hence, additional verification was desirable.…”

In VitroInhibitory and Cytotoxic Activity of MFM 501, a Novel Codonopsinine Derivative, against Methicillin-ResistantStaphylococcus aureusClinical Isolates

“…However, pyrrolidine alkaloids carrying an aromatic substituent on the ring are of a rare class found in nature [ 12 ]. Codonopsinine and codonopsine isolated from Codonopsis clematidea are two examples in this unusual category [ 13 , 14 ]. The aerial parts of this perennial herb, commonly known as Asian bellflower, have been reported to contain both of these compounds which exhibited antibiotic and hypotensive activities and low toxicity level and do not affect the central nervous system [ 15 ].…”

A Short, Efficient, and Stereoselective Total Synthesis of a Pyrrolidine Alkaloid: (−)-Codonopsinine

“…These two compounds display antibiotic as well as hypotensive activities without affecting the central nervous system in animal tests . After structural characterization, 3b, they were revealed to be a new class of simple pyrrolidine alkaloids possessing 1,2,3,4,5 penta-substituted pyrrolidine structures bearing four contiguous stereogenic centers, which are situated in all trans positions. The absolute configuration of the natural antibiotic 1 was determined as (2 R ,3 R ,4 R ,5 R ) .…”