Date: Wed, 19 Mar 1997 05:23:42 -0500 (EST)
From: Chris Jenks <jenks>
To: Multiple recipients of list <>
Subject: Re: CHEMISTS - HELP!

At 03:58 PM 3/18/97 -0500, you wrote:
>Does Ibogaine come only in the L form or is there a D form?
>I have been informed that Ibogaine only comes in the L form.  I just had a
>conversation with a third researcher who confirms this and adds that D forms
>have not been synthesized. Voacangine conversions to Ibogaine would not
>produce both D and L forms of Ibogaine but, only L forms.
>Comments welcome.

  First, to define some terms. Something is "chiral" if it looks different
in a mirror, such as a right hand. In this case, the left hand would be the
"enantiomer" of the right hand, appearing as its reflection. When polarized
light passes through an identical set of chiral molecules, it rotates to an
extent particular to the type of molecule. If the molecules are replaced by
their enantiomers, polarized light would be rotated the same amount but in
the opposite direction. This is called "optical rotation". The polarized
light does not rotate when passed through equal amounts of the two
enantiomers, also known as a "racemic mixture".
  A rule in organic chemistry is that to make only one enantiomer of
something requires the use of one enantiomer of chiral ingredients or
catalysts, otherwise a racemic mixture will be obtained. Some chiral
molecules can be converted easily to their enantiomers, but unless this is
done by something chiral the conversion will stop half way, and a racemic
mixture will result. This process is called "racemization".
  Voacangine isolated from a plant will be one enantiomer, probably the
same orientation as ibogaine, because the enzymes which make things in
plants are one enantiomer. If anyone can propose a feasible synthetic route
from one enantiomer of voacangine to racemic ibogaine, or even a way to
racemize ibogaine, I'll eat my lab coat! The trouble is, to racemize
ibogaine requires it to turn inside out, breaking two of its strongest
bonds in doing so. It isn't going to happen.
  The possibility of racemic ibogaine being synthesized from, say,
5-methoxyindolacetic acid, is quite feasible, as the following reference
suggests. The reason is that the ingredients used in this synthesis are not
chiral, and thus look the same as their mirror images, and no single
enantiomers were employed anywhere during the synthesis. Since there was
nothing to make one enantiomer form faster or easier than the other, equal
amounts of both were obtained.

Claus Herdeis and Claudia Hartke-Karger, "Short and Stereoselective
Synthesis of (+/-)-Ibogamine via a Vinylsulfone Intermediate, IV", Liebigs
Ann. Chem., 1991, 99-104.

   The (+/-) refers to the lack of rotation for polarized light. It would
be feasible to test a sample of ibogaine to see which enantiomer, if
either, it is. Place two polarized filters, such as used in sun glasses or
LCD displays, on either end of a narrow, glass, flat-bottom test tube and
place a light below the bottom filter. Fill the tube with ethanol for any
form of ibogaine, or water for an ibogaine salt. Orient the top filter
until it blocks all light passing through the bottom filter and record its
position. Dissolve ibogaine in the test tube and compare the position
needed by the top filter to block light with its previous position - it
should need to be turned counterclockwise, according to the Merck index.
  Fortunately, there is an even easier way - measure the melting point of
the ibogaine. Ibogaine hydrochloride melts at 299-300 degrees celsius with
decomposition when one enantiomer is involved, while the base melts at
152-153. Racemic ibogaine will melt at lower temperatures, as will impure
ibogaine, which will also melt over a greater temperature range.
If a sample of only a few milligrams of trustworthy, pure ibogaine from a
natural source can be obtained, finding that an equal mixture of it with
the sample in question melts at the same temperature as either before
mixing would strongly suggest that they are identical.
  While looking through papers for syntheses of ibogaine I came across your
ibogaine treatment patents, which claim in part:

  "A single treatment or series of treatments of ibogaine, ibogamine,
tabernanthine or their salts or derivatives in doses ranging from 1 mg/kg
to 60 mg/kg, administered orally or rectally interrupted the use heroin,
cocaine, alcohol, nicotine, methadone, caffeine, amphetamines or
desoxyephedrine in various combinations for one to eighteen months or
longer." (sic)

  I didn't know that! I would very much like to know about the efficacy of
ibogamine or tabernanthine, or their derivatives, compared with that of
ibogaine in human subjects. This brings up another possible explanation for
treatments taking less ibogaine in the sixties - maybe the ibogaine then
was less pure, contaminated by more potent alkaloids. There is no reason to
think that ibogaine is the most potent alkaloid in T. iboga just because it
happens to be greatest in amount.

              Hope this helps.

                   - Chris