Stereochemistry of febrifugine. II. Evidence for the trans configuration in the piperidine ring

Abstract

1.80 1.75 oc2h6 1.82 1.76 OCH(CH3)2 1.88 1.82 ch3 2.23 0.96 2.11 0.82 " 10% toluene solutions except for the 3-methyl compound which was 50% in chloroform. Chemical shifts given in (parts per million) from tetramethylsilane.A 30% solution shows the peaks shifted to 1.84 and 1.88 with incomplete resolution. The results were similar in benzene and for the other alkoxy substituents. In the case of the 3-methyl analog, the peaks were at 2.11 and 2.23 in CHC13 for the trans and cis isomers. When toluene is the solvent, care must be taken to avoid interference from the spinning side bands of the solvent methyl group.

Re-revision of the Stereo Structure of Piperidine Lactone, an Intermediate in the Synthesis of Febrifugine

“…Ozonolysis of 4, followed by PCC oxidation afforded cis-piperidine lactone (cis-5) with a cbz group. Hydrogenolysis and benzoylation of cis-5 gave cis-3, which has the same 1 H-NMR spectrum as reported by Barringer et al 11) Each proton on the bridge-head of cis-3 in the 1 H-NMR (60 MHz) spectrum was observed at d 4.69 and 5.15 ppm, with a coupling constant of 7.7 Hz ( Table 2). …”

“…Subsequently, their relative 6) and absolute 7) structures were proposed, based on Baker's synthetic work. [8][9][10] The relative configuration 11) of (ϩ)-1 was corrected in 1973 and then the absolute structures 12,13) of (ϩ)-1 and (ϩ)-2 were corrected in 1999. Currently, dramatic medical [14][15][16][17] and synthetic [18][19][20][21][22][23][24][25] studies of (ϩ)-1 are in progress.…”

Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds

“…Compound 3 or its open chain analogues b-amino-g-hydroxy carboxylates are active components of many biologically active natural products, such as antifungal/antibiotic peptides [16] and antimalarial alkaloids, [17] as well as active pharmaceuticals, such as gastroprotective drugs [18] and inhibitors of phosphodiesterase [19] and HIV-1 protease. [20] Apart from being associated with biological as well as pharmaceutical activities, this structural subunit is also used in preparing functionalized b-amino acids, [21] oxazolidinones, [22] and aziridines.…”

7-Hydroxyechinozolinone, a New Alkaloid from the Flowers of Echinops echinatus

“…During the literature survey, it was found that the H-2 signal of febrifugine, a 3-substituted (3H)-quinazolin-4-one derivative having antimalarial activity, appeared at 8 8.91 in its hydrochloride (6). This was further confirmed by the 1H-nmr study of synthetic echinozolinone hydrochloride, in which H-2 appeared as a singlet at 8 8.90 (unpublished results).…”