ChemInform Abstract: FURTHER INVESTIGATION OF THE CHEMISTRY AND STRUCTURE OF ANGUSTIFOLINE AND ITS DERIVATIVES. PART V. THE CONFORMATION OF ANGUSTIFOLINE AND ITS SIMPLE DERIVATIVES

Abstract

Abstract Most of the structural assignments presented in this paper were based on the conformation of angustifoline selectively deuterated at the 13β position (13β2H I). To confirm the absolute stereoselectivity of the reaction introducing 2H at 13C on the β face, 13β2H I was transformed into four deuterated derivatives of I and sparteine, the structures of which have previously been determined (in two cases by X-ray analysis). Angustifoline (I), dihydroangustifoline (II) and deoxyangustifoline (V) exist exclusively in the all-chair conformation, in which the 12NH bond and allylic chain are axial, and the lone pair of 12N equatorial. The unusual orientation of the NH bond in the piperidine fragment is stabilized in V by an intramolecular hydrogen bond, but there is no clear evidence as to which factors stabilize this conformation in I and II. The NH protons in I and II are inaccessible to self-association and hence their spectroscopic properties (IR, 1H NMR) differ considerably from those of “normal” piperidine derivatives. N-methyl- and N-cyanomethyl-angustifoline (III and IV) exist predominantly in the all-chair conformation, with the N-methyl (or N-cyanomethyl) substituent equatorial, and the lone pair at 12N axial. The infrared evidence is in full agreement with the X-ray data for a single crystal of IV. Drastic differences between the conformation of III and IV and that of lupanine (VIII) make it possible to discuss the factor responsible for the conformation of the flexible cis quinolizidine moiety in the molecule of sparteine and its derivatives. Tetrahydrorombifoline (VI) and its 11-cyano derivative (VII), like III and IV, exist in the all-chair cisoidal conformation. The absolute stereoselective exchange of hydrogen atoms by deuterium at 11β, 13β and bis-14 positions makes it possible to establish the contribution of specific ν(CH)app and ν(C2H)app bands to the shape and intensity of the “trans” band. A semi-quantitative measurement of the relative intensities of ν(C2H) bands at ∼2200 and ∼2000 cm−1 in deuterated III and IV gave promising results which could be used for the determination of the conformational equilibria.