"Dilaudid" <ddaayy@[EMAIL PROTECTED]
> wrote in message
news:4781326e$0$22638$4c368faf@[EMAIL PROTECTED]
> Is this guy for real?
>
>
>
> On Methods Concerning the Synthesis of Opium
>
> David Allen Winne
>
>
>
>
>
>
>
> It is within the scope of vision to imagine a day when creation of
> medicinal compounds will be achieved stereochemically. This definition,
> "stereochemical" refers to a multifaceted, multidimensional derivation
of
> molecular compounds through complex interactions inclusive of the entire
> components without first reducing them to their singular constituents.
The
> purpose of this distinction is not to enhance the reader's comprehension
> of stereochemistry rather to demonstrate the author understands the
> similarities and digressions outlined within the discipline of
> stereochemistry as defined1 and the proposal identified herein. Although
> such medicinal advances remain imaginable, there is no proposed
suggestion
> as to when accomplished derivatives of this methodology will finally see
> complete fruition.
>
>
>
> Alkaloids derived through analysis of opium have been quantized and
> isolated to their singular components. Leaving the most potent analgesic
> derived as diacetylmorphine (excluding etorphine etc.derived from
> oripavine, which is also a secondary transformation). It does not take a
> stretch of imagination to draw the conclusion that acetylation of
morphine
> base with acetic acid instead of acetic anhydride will yield
> monoacetylmorphine (in the alcoholic 6-hydroxyl group). This conclusion
> was immediately prevalent when first reviewing the structure of
> diacetylmorphine. It also was not an original conclusion as shown below.
>
>
>
> "6-monoacetylmorphine already has a free 3-hydroxy group and shares
> the high lipophilicity of heroin, so it penetrates the brain just as
> quickly and does not need to be deacetylated at the 3-position in order
to
> be bioactivated; this makes 6-monoacetylmorphine somewhat more potent
than
> heroin, but it is rarely encountered as an illicit drug due to the
> difficulty in selectively acetylating morphine at the 6-position without
> also acetylating the 3-position. This can however be accomplished by
using
> acetic acid with an appropriate catalyst to carry out the acetylation,
> rather than acetic anhydride, as acetic acid is not a strong enough
> acetylating agent to acetylate the phenolic 3-hydroxy group but is able
to
> acetylate the 6-hydroxy group, thus selectively producing 6-MAM rather
> than heroin."(http://en.wikipedia.org/wiki/Monoacetylmorphine).
>
>
>
> Considering an objective to obtain opiate derivatives through
> acetylation of raw opium, stochastically deriving potent analogs,
without
> first isolating the constituent components, a reasonable analogy being
the
> process of learning to play a musical instrument, the student must at
> first learn to identify single notes (and fractions thereof), then
scales,
> and finally chords. Through years of study and instruction, the student
> may then choose which notes fall into harmonious or dissonant
conclusions
> within the musical piece being created. Notably, the most colorful
> passages of a piece being assembled from the synthesis of notes falling
> within as well as without the prospective scales inside the structure of
> the key of the piece of music, it is these "blue" notes that create the
> very essence of the artistic effort, through emotions of the author.
> Within the strictest confines of the theory and application, these notes
> may not fit, however, without them the piece is reduced once again to a
> mere scale devoid of artistic emphasis or im****t. Such is the nature of
> all great human endeavors.
>
>
>
> To great benefit, years of effort have been put forth obtaining and
> reducing compounds to their lowest common denominators by isolating
> im****tant discoveries and enabling humankind to grasp the building
blocks
> of molecular compounds. The process requires this most tedious and
devoted
> effort to isolate and identify interactions at their very basic
> fundamental level. Chemicals such as morphine, codeine, hydrocodone,
> hydromorphone, and so on, have provided incalculable benefit to the
human
> species. Additionally, the process may through necessity continue
unabated
> over the next several hundred years only to find completion upon
> exhaustion of all potential isolations and reductions available. This
> leaves the origin of chemical analysis in its infancy at present just
> beginning to crawl and upon mastery then to begin walking prior to a
> steady run. Once again to begin recombination of essential singular
> molecular compounds one by one until all necessary derivatives have been
> catalogued a second time over. The final arrival at stereochemical
> projection of complex molecular compounds recombining in a quaternary
> synergy only obtained through three-dimensional interactions
intrinsically
> integral to the unique recombination of the original complex molecular
> compounds themselves a fingerprint unique specifically to each
individual
> synergistic interaction.
>
>
>
> Diacetylmorphine in and of itself appears a stereochemical compound
> with the acetylation of morphine base with acetic anhydride creating two
> isomers of monoacetylmorphine. This synthesis does not appear
synergistic,
> for example, a chemical compound expressing a synergistic effect would
be
> hydrocodone mixed with aspirin (or acetaminophen). The synthesis of the
> two compounds creates a synergistic effect elevating the strength
through
> lesser amounts of either component (although not stereochemical). This
> does not have any relevance upon the stereochemical composition of
> diacetylmorphine merely that the "di"-acetylation synthesis bears no
> significant synergistic contribution (and is likely accidental). This
> distinction is critical in relation to this papers definition given for
> stereochemistry. The stereochemical composition of diacetylmorphine with
> the necessary inclusion of two isomers of 3-monoacetylmorphine and
> 6-monoacetylmorphine yields the appropriate non-reactive isomer
> 3-monoacetylmorphine as a chiral counterpart to the reactive
> 6-monoacetylmorphine. This is congruent to the acetic anhydride
molecules
> mirror-like stereo projection of two acetic acid molecules prior to the
> acetylation of morphine base into diacetylmorphine. While the
> interrelation****p of the chemistry outlined is consistent with the
> classical definition of stereochemistry. It digresses for clarity of
> purpose when understanding proposed methodology, the indicated method
> herein being a "stereochemical" approach to stereochemistry. A
quaternary
> enterprise entertaining the process of visualizing the entire molecular
> compound from every direction at once as well as attempting to parallel
> isomers with chiral counterparts and potential inclusion of racemization
> of one enantiomer into another.
>
>
>
> The intent and purpose of synthesizing complex molecular compounds
in
> one transition is to obtain the additional benefit of a multidimensional
> synthesis as outlined above. Taking advantage of one molecular
transition
> as well as the additional benefit of a second transition only available
> due to the complex molecular compound and the state of flux created upon
> the initial transition phase. This enables a molecular transition unseen
> in simple compound composition due to the absence of multiple molecular
> transitions being available. Not only does the complex molecular
compound
> transform but also as it is transforming, the state of transition opens
> op****tunities for additional molecular transitions unforeseen in any
> simple molecular compound transaction. This effectively creates
limitless
> potential parameters for the ac***ulation of medicinal compounds. The
> actual limit is defined by the ability of the human being to predict and
> derive the necessary transitions required and attempt to verify them
> through experimentation. It is as the three-body problem in classical
> physics, anything beyond becomes too difficult to calculate in terms of
> obtaining a useful result.
>
>
>
> Returning once again to our musical analogy, scales comprised of
> specific root notes retain both their major and minor properties
enabling
> entirely different moods to become prevalent by mere redesignation of
the
> root note. Taking this to its furthest extent enables modal use of
scales
> thereby creating twelve uniquely different scalar functions through the
> alternative assignment of root notes. Hence, Aeolian, Ionian, Phrygian,
> Lydian, Mixolydian, and Dorian modes etc.are derived from one scale at
> numerous root positions. This very same modal composition can be applied
> to any molecular compound thereby deriving several different components
> with unique properties by simply manipulating the key atom in the root
> position. This can go on indefinitely without end effectively creating a
> "harmony of the spheres" sufficient to roll Johannes Kepler in his
grave.
>
>
>
> Additionally, in congruence with musical analogy is the necessary
> inclusion of harmonic, tonic, and diatonic triad inversions equating to
> the chemical conversion of a single molecular compound into a
> stereochemical product. The result includes the necessary construction
of
> "Chords" the musical equivalent of "stereochemically" doing
> stereochemistry.
>
>
>
> Effectively, the result is working with complex molecular compounds
> attempting to synthesize key components within, three-dimensionally,
> remains the equivalent, of chord building technology in music theory.
> Naturally imagining a musical product entirely devoid of chords is the
> equivalent of investigating modern advances in chemistry. We are at the
> scale and note building phase of the industry. Only time can tell when
> medicines derived from chorale counterparts becomes available.
Certainly,
> anyone can pick up a pile of pills, swallow them, and experience several
> diverse effects (both good and bad). This is exactly why it will take so
> long to accomplish the necessary analysis and understanding of chemical
> compounds. Very few people would appreciate the consequences of such
> activity necessitating appropriate precautions in effect in current
study
> of molecular compounds.
>
>
>
> The inclusion of all opium alkaloids creates cir***stances both
> complimentary and contradictory in nature imparting a synergy not
apparent
> through isolation of specific compounds, metabolites, or isomers. The
> author makes no pretense in the assumption that synergistic compounds
will
> be produced through the intended approach; merely that it is a
> distant-future possibility. A possibility that awaits progress obtained
> only through diligent isolation of endless singular molecular compounds
> and recombination of those compounds with endless others developing a
> broad enough foundation to begin contemplation of elevated synthesis of
> complex molecular compounds.
>
>
>
> Summary:
>
>
>
> The purpose behind the approach envisioned is summarized through
> experiences related to the administration of pharmaceutical compounds
> derived and isolated from opium alkaloids. Examples such as hydrocodone,
> morphine, codeine, and oxycodone all have limited useful parameters such
> as fast onset with short duration or limited (not to be confused with
> potent) psychoactive properties in comparison to simple opium extract
> containing the entire spectrum of alkaloids.
>
>
>
> In addition, the after effects of any of these pharmaceuticals leave
> one feeling "strung out" or "hung over" in comparison to basic opium
> extract. A large degree of this feeling is attributed to some of the
> additive ingredients typically associated with some opiates such as
> acetaminophen, aspirin, etc.However; the entire effect is not
attributable
> to the additives. Moreover, extensive analysis of the properties of
these
> isolated compounds derived for medicinal use tends to leave the
impression
> (rightfully so) of specific medicinal focus. Specifically, they tend to
> hit hard and taper off fast opposed to a slower onset with longer
> duration.
>
>
>
> The experience increases in pro****tion to use of these
pharmaceuticals
> adjunct to pure opium extracts. I.e. using opium extracts daily then
> switching over to pharmaceuticals conveys an effective sense of the
> limitations imposed through isolation of specific alkaloids. An analogy
> would be suggesting that one took morphine, codeine, and thebaine
> (hydrocodone, acetyldihydrocodeine, oxycodone, and oxymorphone) all at
> once. It readily becomes evident exactly how strong and effective opium
is
> with its complete compliment of alkaloids. However, the effects of the
> pure opium extract are subtle as well as powerful and the observed onset
> of analgesia is decidedly weak in comparison to certain isolated
> derivatives above.
>
>
>
> It is with this observation that an attempt to synthesize
constituent
> components included within opium, eliminating certain intermediary
> transitions is intended to satisfy potential objectives otherwise
> accomplished through isolation of specific compounds. Notably,
acetylating
> the 6-hydroxyl group in morphine alone will sufficiently amplify the
> pharmacological effects of raw opium. Additionally, the extraction and
> isolation of compounds such as morphine from opium derived from dried
> poppy pods becomes somewhat pointless since the overall effect of the
> product is generally stronger and less time consuming. It merely is not
as
> analgesic as the isolated compounds (this is due largely in part to the
> degree of consumption) when taken in concentration.
>
>
>
> Method:
>
>
>
> The first time the author-extracted alkaloids from the opium poppy, a
> container of extract decanted from dried, ground pods placed within an
> Espresso machine and run through with a solution of 5% acetic acid. The
> solution obtained therein placed upon a burner and simmered slowly until
> all evidence of liquid eva****ated. The crystalline residue obtained by
> scraping the sides of the container ignited within a pipe leaving the
> author feeling happy and well disposed. Upon this occasion, no
substantial
> quantity of material was derived to investigate additional properties
> therein. It is noted that this author knew nothing regarding the
chemistry
> of opium at the time and was merely looking for a more effective way to
> extract tea from poppies.
>
>
>
> On the second occasion this method was conducted, only stems from
the
> Papaver Sominiferum species were used and twelve cups of a solution of
5%
> acetic acid were decanted from a coffee maker (run through twice).
> Approximately 1.5 cups (dry measure) of poppy straw was used. The
solution
> was then placed upon a burner to slow simmer until distillation
> substantially reduced the quantity of liquid therein (approximately
three
> hours). The entire solution was then relocated to a three-cup pot
> (extremely small) to simmer over night. Upon examination, the next day
the
> ½-inch solution had eva****ated to less than a 1/8-inch across the bottom
> with crystalline deposits from the ½-inch mark to the top of the
solution.
> Into this solution was introduced approximately 15 ml of hydrochloric
acid
> with no apparent reaction. Then approximately ½ teaspoon of bicarbonate
of
> soda was added to the mixture causing the entire pot to foam for about
ten
> minutes. Soon thereafter, introducing a small round brush (made of
> horsehair) into the liquid rapidly stirring caused the mixture to die
down
> to a viscous state.
>
>
>
> Letting the pot sit for about ten minutes, the author then began
> rotating the pot twisting the liquid at a 45-degree angle thereby
causing
> the liquid to rise upon the walls eva****ating rapidly and quickly
becoming
> a uniform paste. The pot was then cooled while the paste was obtained
upon
> a small putty knife, (the material collected amounted to approximately a
> teaspoon). In addition to the Brown paste-like substance, was a hard
> crystalline deposit along the bottom ½ inch of the side of the pot (it
is
> likely that the paste would have become crystalline if left
undisturbed).
> This material was chipped away yielding a thimble full of material. The
> material placed within a pipe and smoked left some small effect upon the
> subject. The additional consumption of four pea-size rolled balls of
paste
> left the author with exceptional sensitivity to light and some
> urine-retention effects. Compounding this feeling was a definite
> "opiate-like" state however, the extent of the effects are largely lost
> upon the author's tolerance for opiates. In addition, the degree of
> morphine within the sample is highly suspect since the sample was
> ac***ulated from poppy straw instead of poppy pods, which is the usual
> part kept for the extraction.
>
>
>
> Hypothesis:
>
>
>
> The use of acetic acid when acetylating morphine base creates
> 6-monoacetylmorphine. There is no point with present day knowledge to
> obtain Diacetylmorphine for licit or illicit purposes. The only active
> metabolites derived from the process are 6-monoacetylmorphine, and
> morphine. These metabolites obtained without the additional step of
> creating Diacetylmorphine alleviate the body's metabolism from
> deacetylation of the 3-hydroxyl group maintaining equivalent
> pharmacological results.
>
>
>
> Extending this application to opium extract decanted from poppy pods
> with a solution of 5% acetic acid effectively acetylating the 6-hydroxyl
> group in morphine alone will sufficiently amplify the pharmacological
> effects of raw opium thereby creating a more bioavailable compound for
> use. There remains the additional possibility of a phase transition
> enabling additional alkaloids to become transformed. It remains
uncertain
> if this additional transition will be synergistic or beneficial to the
> overall product. This
>
> "extract" tea from poppies process excludes the possibility of
injectable
> medicinal value without the inclusion of a cleansing and purification
> stage.
>
>
>
> "According to Small and Lutz in The Chemistry of the Opium
Alkaloids,
> a re****t commissioned by the U.S. Public Health Service in 1932, "when
> morphine is heated with acetic anhydride two acetyl derivatives are
> formed; [alpha]-acetylmorphine and ß-acetylmorphine probably have
> respectively the phenolic and alcoholic hydroxyl groups acetylated."
That
> is, [alpha]-acetylmorphine is 3-monoacetylmorphine (3-MAM) and
> ß-acetylmorphine is 6-monoacetylmorphine (6-MAM)."
>
>
>
>
>
>
>
> [On the Action of Organic Acids and their Anhydrides on the Natural
> Alkaloids. C.R.A. Wright, D.Sc., Lecturer on Chemistry, St. Mary's
> Hospital Medical School, London. (Journal of The Chemical Society, Vol.
27
> (1874), pp. 1031-1043.)]
>
>
>
> Conclusion:
>
>
>
> One of the most significant advances in modern medicine in the
> nineteenth century was the stereochemical synthesis of diacetylmorphine
> from morphine. This is clearly demonstrated by the relative order of
> magnitude increase in the strength of the final product. The fact that
the
> greater majority of modern medical institutions elect to leave this
> solution out as an analgesic choice for their patients serves as tacit
> confirmation of the significance of stereochemical product strength.
>
>
>
> While this fact may be evident in the case of diacetylmorphine, the
> real objective is to obtain moderate synergistic effects from complex
> molecular compounds through enhancement of existing properties of their
> alkaloid origin. This selective method hopes to enhance the effective
> properties of the chemistry without losing the inherent natural basis of
> origin. The summary of contents in chemical analysis in this approach
> hopes to accomplish greater results with less of the side effects that
> plague methodologies using isolation and reduction tactics.
>
>
>
> Isolating diacetylmorphine from its parental alkaloid group strips
it
> of any redeeming properties found within the other constituents. This
> fundamental failure contributes to its overwhelming success in the
> strength category while stigmatizing its benefit with the addictive
stigma
> that may have otherwise been avoided had the entire alkaloids properties
> been retained. This is not intended to suggest that addictive properties
> would no longer be present merely that they may not have been magnified
to
> such great extent with additional opposing alkaloid components.
>
>
>
> 1. "Stereochemistry, a subdiscipline of chemistry, involves the study of
> the relative spatial arrangement of atoms within molecules. An im****tant
> branch of stereochemistry is the study of chiral molecules,"
> http://en.wikipedia.org/wiki/Stereochemistry
>
>
>
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