Tadeusz Brukwicki

Conformational equilibria in quinolizidine alkaloids

Abstract A method involving 1H and 13C NMR spectroscopy was used for quantitative determination of conformational equilibria in 12 bis-quinolizidine alkaloids and their two salts. In view of the three criteria, i.e. 13C chemical shifts for C12 and C14 as well as the coupling constant H7H17β, the results were consistent. The coupling constant H7H17β was valid also for three-ring quinolizidine-piperidine alkaloids. Factors influencing the equilibria were discussed.

A comparative study of NMR chemical shifts of sparteine thiolactams and lactams

Abstract The 13 C and 1 H NMR spectra of the four possible thiolactams of sparteine ( 1 ) were recorded and the thiolactam group effects were determined. Most of the effects are greater than those of the lactam group in the oxo analogs. A good linear correlation between the 13 C chemical shifts of CS and those of CO was found. The effects could help in assignment of the spectra and determination of conformation of thiolactams and related thiocarbonyl compounds.

NMR spectra and geometry of epi N-oxides of sparteine and some of its derivatives in solution

Abstract Four epi N-oxides of sparteine and its derivatives were prepared (13α-hydroxysparteine epi N-oxide ( 3 ) and 13α-hydroxylupanine N-oxide ( 5 ) for the first time) and their 1 H and 13 C NMR spectra were assigned using two-dimensional techniques. As sparteine ( 1 ) and 13α-hydroxysparteine ( 10 ) are conformationally homogeneous and their epi N-oxides 2 and 3 retain the same conformation (with a boat ring C), the N-oxidation effect could be determined better than before in this class of compounds. The hydroxyl group and lactam effects were also determined. The HCCH angles calculated for 2 , 3 , 4 , and 5 using the generalized Karplus equation are consistent with those obtained by X-ray diffraction for two salts of 2 .

The first quantitative determination of conformational equilibrium in quinolizidine-piperidine alkaloids

Abstract The fraction of the conformer with the boat ring C in the conformational equilibrium in N-methyl-angustifoline (7) in chloroform and benzene solutions was determined to be ca. 34% using coupling constant J7–13β. In angustifoline (5) J7–13β could not be determined directly from the spectra; a simulation gave the result of 4.25 Hz corresponding to ca. 23% of the boat conformer. In tetrahydrorhombifoline (6), rings B and C have a chair conformation. Low temperature 13C NMR measurements seem to corroborate these results qualitatively. Factors influencing conformational equilibria are discussed.

Geometry of tricyclic quinolizidine-piperidine alkaloids in solution by NMR spectroscopy

Abstract The Haasnoot equation was used to determine HCCH spectroscopy dihedral angles from 1H NMR spectroscopy in tricyclic quinolizidine-piperidine alkaloids in solution: seco(11,12)- 12,13-didehydromultiflorine (1), seco(11,12)- 5,6-didehydromultiflorine (2) and angustifoline (3). Ring C in the three alkaloids has quite a regular chair conformation. Ring B is a flattened chair in 1 and 3 and a sofa in 2. The geometry of 2 is similar to that of cytisine (4).

Lupin alkaloids Part IV. The influence of some structural factors on the conformational equilibrium in bis-quinolizidine systems

Abstract 13 C NMR and IR spectra of minor alkaloids of Lupinus albus such as multiflorine ( I ), 13α-hydroxymultiflorine ( IV ) and their monoperchlorates, 13α-hydroxy-5-dehydromultiflorine ( V ) and 5-dehydromultiflorine ( VI ) were taken. I and IV in CDCl 3 , their monoperchlorates in CD 3 CN and V in CD 3 OD solution occur in conformational equilibrium. The share of the conformation with a boat ring C in I is about 74%, in IV 67%, in I · HClO 4 20%, in IV ·HClO 4 3% and in V 3%. The change in conformational preference results mainly from a decreasing destabilization of the conformation with a chair ring C caused by an increase in the distance between the interacting hydrogen atom pairs 5α–17α, 8β–12β, 12β–17β and 14β–17β, due to protonation induced lengthening of the N (16)-C α bonds. VI and most of the molecules of V remain in solution in conformation with a chair ring C. This conformation in V and VI is less destabilized than in I and IV because of a lower steric hindrance for the chair ring C, as a consequence of the planarity of ring A and a part of fragment B and because of the absence of the 5α–17α interaction.

Quantitative determination of conformational equilibria in 3,7-diazabicyclo[3.3.1]nonane derivatives

Abstract A method of quantitative determination of a conformational equilibrium in 3,7-diazabicyclo[3.3.1]nonane (bispidine) derivatives is described. It is based on a comparison of coupling constants J 1−2 β and others with the corresponding ones from the models of pure conformers. 3-Benzyl-7-methyl-3,7-diazabicyclo[3.3.1]-nonane ( 4 ) proved to exist mainly in a double-chair (CC) conformer, although there is also a significant contribution of chair-boat (CB) and boat-chair (BC) conformers. In 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one ( 5 ), a CB conformer predominates over significant amounts of BC and CC.

The structure of angustifoline, an alkaloid ofLupinus angustifolius, in solution

SummaryThe1H and13C NMR spectra of the lupin alkaloidangustifoline1 in four solvents (cyclohexane-d12, CDCl3, CD3CN, and C6D6) were assigned using 2D H,H and H,C COSY and 2D J-resolved spectra. The torsional HCCH angles calculated from the vicinalJHH coupling constants are essentially in agreement with those expected for the deformed all-chair conformation withendo oriented N(12)-H bond, reported earlier for1 in the solid state. Some arguments seem to point, however, to a small contribution of other conformations: with ring A deformed in another direction, deformed all-chair withexo oriented N(12)-H bond and/or a conformation with ring C in the boat form.ZusammenfassungDie1H- und13C-NMR Spektren des Lupinalkaloids Angustifolin (1) in vier Lösungsmitteln (Cyclohexan-d12, CDCl3, CD3CN und C6D6) wurden mit Hilfe von H,H-COSY-, C,H-COSY und 2D-J-aufgelösten Spektren zugeordnet. Die aus den vicinalen Kopplungskonstanten berechneten Torsionswinkel stimmen mit den für eineall-chair Konformation mitendo-orientierter N(12)-H-Bindung erwarteten und für1 im festen Zustand bereits berichteten überein. Es liegen allerdings auch Hinweise auf geringe Beiträge anderer Konformationen vor: deformierter Ring A, verformteall-chair-Konformation mitexo-orientierter N(12)-H-Bindung und/oder Boot-Konformation von Ring C.

Lupin alkaloids: Part II. Some stereochemical aspects of multiflorine and seco(11,12)-12-dehydromultiflorine previously named N-methylalbine

Abstract From the 13 C NMR spectra of multiflorine ( I ), seco(11,12)-12-dehydromultiflorine ( II ) and their monoperchlorates (in DMSO- d 6 ), the conformation of rings B and C was determined. In the free base of I they are, boat-chair, whereas in the monocation of I as well as both in the free base and the monocation of II , they are chair, chair and chair respectively. The difference in conformation of the two free bases, I and II , is probably due to a repulsive interaction between the hydrogen pairs 8β−12β, 12β−17β and 14β–17β in the “chair” conformation in I . In I ·H + a weak intramolecular hydrogen bond stabilizes the triple-chair conformation.