Comments and further observations on the structure of eserine (physostigmine).

Abstract

Petcher and Pauling have reported1 the results of an X-ray investigation of the crystal structure of the alkaloid eserine (physostigmine) in which they established the absolute configuration of the alkaloid about the B/C ring junction and at the N(l)-CH3 and N(8)-CH3 groups to be as shown in I (R = CH3, X = NCH3). These authors erroneously state, however, that this absolute configuration had previously2 been “confirmed by use of the nuclear Overhauser effect (NOE) in NMR spectroscopy”, whereas such studies had, in fact, only established the relative configuration of the B/C ring junction (which had previously3 been deduced from a study of the geometry of the molecule) and the relative configuration of the N(1)-CH3 and N(8)-CH3 groups. Further, Petcher and Pauling1 disregard the earlier published chemical studies4, 5 which four years previously had independently and by different routes established the absolute configuration of the B/C ring unction in physostigmine to be as shown in I (R = CH3, X = NCH3), a fact that their X-ray studies only further confirmed. Longmore and Robinson5 further established, primarily from the results of comparative ORD investigations, that the absolute configuration about the B/C ring junction of the alkaloids N(8)-norphysostigmine, physovenine and eseramine is as shown in I (R = H, X = NCH3, R = CH3, X = O, and R = CH3, X = N.CO.NHCH3, respectively). The results of earlier related studies6, 7 on geneserine, which before 1969 (ref. 8) was thought to have the structure of physostigmine N(l)-oxide, showed it to have the absolute configuration as depicted in II, the indicated cis relationship of the N(l)-methyl group and the C(2)-proton being that which predominates at 20°C (ref. 6).