X-ray diffraction of alkaloids

Quinolizidine alkaloid analysis also utilizes the X-ray method, which is based on the absorption of X-rays, diffraction of X-rays, wavelength, and radiant power measurements of X-rays. When an atom is excited by the removal of an electron from an inner shell, it usually returns to its normal state by transferring an electron from some outer shell to the inner with the consequent emission of energy as an X-ray. The X-ray method is applied to quinolizidine alkaloids which have a crystalline form. In this sense it is the same as the RTG methods, which can be applied only to crystalline materials. X-rays can be absorbed by material and this gives rise to X-ray absorption spectra . The spectrum provides material for the identification of compounds. 

The relative stereochemistry of stephadiamine (16) was clarified by X-ray diffraction analysis, using the direct method, and the absolute configuration was solved by the heavy-atom method, using the N-p-bromobenzoyl derivative (6). Stephadiamine (16), a C-norhasubanan alkaloid, is not regarded as a hasubanan congener in the strict sense, but as a new member of oe-amino acid derivatives (6). 

Bisquinolizidine alkaloids have also been widely studied by this technique. For instance, the crystal structure of (—)-A16(17 ,-dehydrolupaninium perchlorate 23 was obtained from sealed-tube and synchroton X-ray diffraction data, and showed that the A, B, C, and D rings assume distorted half-chair, chair, distorted sofa, and chair conformations, respectively it was also used to determine the most precise dimensions so far known for the iminium group <1999JST245>. The crystal structure of quinolizinium hexafluorophosphate has also been studied <2001CSC174>. 

The configurations of the stereo centers for ervatamine alkaloids were established by chemical correlations (189, 190) with the vobasine series and supported further by an X-ray diffraction study of 44 (191). 

The X-ray diffraction studies have not only helped in elucidating the complete structure of a compound in its crystalline state but also in establishing its configuration. The noteworthy feature of the method is that no recourse is taken to chemical work. Thus the structure of the alkaloid the-lepogine, C20 H31NO has been settled without chemical work. For the last two decades the method has been widely employed because it takes less time due to the use of automatic diffractometers and electronic computers. 

The first alkaloid based on these ring systems was discovered in 1992 in the European species Exochomus quadripustulatus.Aiter recrystallization of its hydrochloride salt, a single-crystal X-ray diffraction study of exochomine (18) established the structure and absolute configuration of this alkaloid [32]. 

A third alkaloid of this type, chilocorine B (20), was isolated from C. cacti. In this molecule, NMR experiments showed that the 2-methylperhydro-9i -aza-phenalene and the 3,4-dimethyloctahydro-8b-azaacenaphtylene subunits are linked in a spirocyclic fashion. An X-ray diffraction analysis fully determined the structure and relative stereochemistry of this alkaloid [34]. 

The roots of the same plant has yielded one new alkaloid together with two known compounds lycoctonine and lappaconitine. The structure of the new alkaloid (cochlearenine) (11) is quite similar to that of cochleareine (9). Due to this resemblance the stracture determination of the compound 11 was carried out not only by spectral data but also by single-crystal x-ray diffraction studies [19]. 

Moreover, polycyclic indole alkaloid-type molecules 225 with a ketopiperazine were prepared by Wang et al. using Ugi-Pictet-Spengler process [68]. Ketocar-boxylic acids 227 were used as bifunctional substrates in Ugi reaction to yield lactams of varying ring sizes (Scheme 41). A diastereomer of hexacyclic indole derivative was crystallized and yielded X-ray diffraction suitable crystal to assign the stereochemistry. 

The marine hydroid Tridentata marginata contained the aromatic alkaloids tridentatols A-C (186-188). Tridentatol A (186) inhibited feeding by the planehead filefish. The structure of tridentatol C (188) was elucidated by a single crystal X-ray diffraction study [179]. 

Croomine is a major alkaloid of the roots and rhizomes of Croomia heterosepala. Its structure (10) has been settled by its chemical reactions and spectroscopic properties, and confirmed by X-ray diffraction analysis of its methiodide. On mild oxidation (dehydrogenation) with silver oxide, the alkaloid affords the corresponding pyrrole.8... 

Hetisine (125) was isolated as a minor alkaloid from the roots of A. heterophyllum Wall (80) in 1942 by Jacobs and Craig (118, 119). Later it was also isolated from D. cardinale Hook (120). Several papers were published (121, 122) regarding the chemistry and structure elucidation of hetisine, but the structure of hetisine (125) was eventually established by an X-ray diffraction study (123, 124). Earlier work on the chemistry of hetisine has been reviewed in Volume XII of this treatise (6). 

In 1991, Cardellina, II and co-workers isolated clavepictines A and B from the tunicate Clavelina picta, and these alkaloids showed substantial cyctotoxic activity against human solid cell lines. In the same year, Faulkner and co-worker isolated pictamine, the bis-nor congener of clavepictine A, from the same marine species. Although the relative stereochemistry of these alkaloids was determined on the basis of extensive NMR studies for clavepictine A in conjunction with X-ray diffraction analysis for clavepictine B, the absolute stereochemistry of these alkaloids was unknown. 

Sceletium Alkaloids.—(-)-Mesembrane has been isolated from S. namaquense L. Bolus X-ray diffraction analysis of its hydrochloride monohydrate revealed its relative and absolute configuration (10). (-)-Mesembrine has the absolute configuration (11), in accord with (10), and it is now firmly established that alkaloids of this family belong to a single antipodal series.13... 

Anatoxin-a is a toxic alkaloid occurring in the filamentous blue-green alga Anabaena flos-aquae and has been responsible for fatalities amongst livestock and wildlife. Mass and n.m.r. spectroscopy, and X-ray diffraction analysis of its N-acetyl derivative, pointed to structure and absolute stereochemistry (12) for ana-... 

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