S. William Pelletier

Reversal of absolute stereochemistry of the pyrrolo[2,1-b]quinazoline alkaloids vasicine, vasicinone, vasicinol and vasicinolone

Abstract The previously assigned 3 R configuration of (−)-vasicinone has been reversed and this pyrrolo[2,1-b]quinazoline-9-one has been shown to have the 3 S -configuration ( 3 ) on the basis of an X-ray diffraction study of (+)-vasicinone hydrobromide. Likewise, the 3 R stereochemistry assigned earlier to (−)-vasicine (peganine) ( 1 ) on the basis of an X-ray analysis of its hydrochloride has also been reversed by reinvestigation of the X-ray diffraction analysis of the hydrobromide. The absolute stereochemistry of the alkaloids (+)-vasicinol ( 2 ) and vasicinolone ( 5 ) which have been inter-related, should also have the 3 S -configuration. A study of the 1 H nmr spectroscopy of (−)-vasicine by the use of Moshers method using MTPA [α-methoxy-α-(trifluoromethyl)phenylacetic acid] esters indicated an exception to this model for establishing the absolute configuration.

New alkaloids from Delphinium elatum L.

Abstract A study of the alkaloids present in the seeds of Delphinium elatum L. has led to the isolation of three new C 19 -diterpenoid alkaloids: elasine ( 1 ), isodelpheline ( 3 ) and eladine ( 5 ), besides seven known alkaloids: delpheline ( 7 ), deltaline ( 8 ), methyllycaconitine ( 10 ), nudicauline ( 11 ), 14-deacetylnudicauline ( 12 ), lycoctonine and elatine ( 13 ). The structures of these alkaloids were determined by spectral data and correlation with alkaloids of established structures. Thus methylation of elasine ( 1 ) and eladine ( 5 ) yielded deltaline ( 8 ) and delpheline ( 7 ), respectively.

Alkaloids of Delphinium barbeyi

Abstract Chemical investigation of the aerial parts of Delphinium barbeyi resulted in the isolation of three new alkaloids, 14-acetyldictyocarpine, barbinine and barbinidine, as well as 13 known alkaloids. Structures and stereochemistry were deduced by spectroscopic methods. The structures of 14-acetyldictyocarpine and barbinidine were confirmed by chemical correlation with dictyocarpine.

13C nuclear magnetic resonance spectroscopy of atisine and veatchine-type C20-diterpenoid alkaloids from aconitum and garrya species

Abstract 13 C NMR spectra of the atisine- and veatchine-type alkaloids, as well as certain of their derivatives, have been obtained by the Fourier transform technique at 25.03 MHz. With the help of single-frequency off-resonance proton decoupling techniques, additivity relationships, and the effects induced by certain structural changes, self-consistent assignments of nearly all the resonances have been made. The 13 C NMR spectra are also analyzed to identify skeletal features of the atisine and veatchine-type alkaloids of use in the structure determination of new C 20 -diterpenoid alkaloids. On the basis of the 13 C NMR analysis of atisine and veatchine as well as a temperature-dependence study of atisine, the existence of C-20 epimers in these alkaloids is demonstrated. A 13 C NMR study of the behavior of the oxazolidine ring of atisine in non-ionic and ionic solvents indicates that the C-20 epimers of atisine do not exist in an equilibrium mixture in solution and are not interconvertible via a zwitterion as reported earlier.

An alumina catalyzed addition of secondary amines to exocyclic α,β-unsaturated ketones

Abstract A Michael addition of secondary amines to exocyclic α,β-unsaturated ketones has been achieved in excellent yield in the presence of alumina. In the absence of alumina, the reaction does not proceed or takes place in low yield with many side products after a long reaction time.

The synthesis of certain 11,14-dimethoxydeoxypodocarpic acid derivatives. an application to the synthesis of (+)-winterin from drimys winteri

Abstract This paper reports the synthesis of several 11,14-dimethoxydeoxypodocarpic acid derivatives from (+)-podocarpic acid. The synthesis of the naturally occurring sesquiterpene, (+)-winterin, from Drimys winteri illustrates a synthetic application of the 11,14-dimethoxy intermediates and establishes the absolute configuration for winterin.

Effect of diterpenoid alkaloids on cardiac sympathetic efferent and vagal afferent nerve activity

The diterpenoid alkaloid, lappaconitine, at a dose of 150 micrograms/kg (i.v.) increased cardiac vagal afferent nerve activity (16.2%) and reduced cardiac sympathetic efferent nerve activity (12.5%). A polar analog, N-deacetyllappaconitine, at this same dose, increased cardiac vagal afferent nerve activity (40%) and reduced cardiac sympathetic efferent nerve activity (23.5%). Both of these agents also reduced arterial blood pressure and heart rate. A larger dose of lappaconitine (300 micrograms/kg i.v.) produced the same changes in nerve activities and cardiac function as the lower dose. Two other structurally related agents, lycoctonine and aconine, failed to alter these variables in doses up to 300 micrograms/kg. These data suggest that certain diterpenoid alkaloids activate autonomic reflex receptors, including cardiac reflex receptors. The polar agent, N-deacetyllappaconitine, appears to be more effective on cardiac reflex receptors than the non-polar agent, lappaconitine. Such agents may be useful in the treatment of hypertension.

Deoxygenation reactions of C19-diterpenoid alkaloids

Efficient methods for deoxygenation of secondary and tertiary alcohols of some C19-diterpenoid alkaloids are presented. Thus deltaline (1) was converted to delpheline (2) or to 10-deoxydeltaline (7); deltamine (8) to 6-deoxydetamine (10); and delpheline (2) to 6-deoxydelpheline (12). An unusual elimination product 4 was formed when chloro-derivative 3 was reduced with LiAlH4.

The structures of four new C 19 - diterpenoid alkaloids from Aconitum forrestii stapf

From the root extracts of Aconitum forrestii Stapf, we have isolated four new alkaloids: acoforine (6), acoforesticine (8), acoforestine (10) and acoforestinine (14), besides crassicauline A, forestine and yunaconitine. The structures of these alkaloides were determined on the basisi of spectral data and correlation with alkotoids of established structures. The structure and stereochemistry of acoforestine (10) was confirmed by an X-ray crystal structuer determination.

The structure of barbeline, an unusual C19-diterpenoid alkaloid from delphinium barbeyi huth

Abstract From the ethanolic extract of Delphinium barbeyi Huth, a novel C 19 -Diterpenoid alkaloid barbeline ( 4 ) has been isolated and its structure determined by spectroscopic data and an X-ray crystal diffraction study. Barbeline is the only example of an alkaloid containing a C(19)=N- azomethine group among the 230 naturally occurring C 19 -diterpenoid alkaloids. Two other new alkaloids, 6-acetyldelpheline and 6-deoxydelpheline, as well as the known alkaloids browniine, delphatine and glaucenine have also been isolated from this plant.