Alkaloidal hydrochloride salts

Generally, alkaloidal salts are insoluble in nonpolar solvents but their free bases are quite soluble in the solvents. Therefore, the basified modifier should be introduced into the SFE to solubilize alkaloids in CO,. For the evaluation of the effects of basified modifiers, diethylamine was added to methanol or water at a 10% (v/v) concentration level. Then, the basified modifiers were continuously incorporated into the extraction cell at concentrations of 1, 5, and 10 % (v/v). The effects of methanol basified with diethylamine as a modifier on the solubilities of hyoscyamine (1) and scopolamine (2) are shown in Figure 8. The addition of diethylamine (10% v/v) into methanol dramatically enhanced the solubilities of the alkaloidal hydrochloride salts compared with those of pure methanol alone. This may be due to the fact that methanol basified with diethylamine changed the salts to the free bases. 

The noraporphine nandigerine, C18H17O4N, was isolated from Hernandia ovigera L. (Hernandiaceae). The base crystallized from methanol either as solvent free needles (mp 176°-177° [ajp - -248° in ethanol), or as plates of the methanol solvate, C]8Hi704N-CH30H (mp 99°-100°). The alkaloid hydrochloride salt melted at 245°-247° (decomp.) (33b). 

During the enantiospecihc total synthesis of ajmalin-related alkaloids, (-)-suaveoline and (-)-raumacline, N-debenzylation of the hydrochloride salt of the alkaloids was performed with 10% Pd/C (0.12 mol Pd/mol compound) in absolute EtOH at room temperature and 1 atm of hydrogen for 1 or 2 hours. When this catalytic debenzylation was performed, however, using 10% Pd/C (0.28 mol Pd/mol compound) in MeOH for 5 hours, N-methyl derivatives were produced in good yield (Scheme 4.91).339,340... 

Once the cocaine has been legally produced from the coca leaf, it is exported to various countries for medicinal use, basically as a topical local anesthetic (applied to the surface, not injected, only treating a particular area). In the United States the crystalline powder is imported to pharmaceutical companies who process and package the cocaine for medical use. Merck Pharmaceutical Company and Mallinckrodt Chemical Works distribute cocaine in crystalline form (Hydrochloride Salt) in dark colored glass bottles to pharmacies and hospitals throughout the United States. Cocaine, in the alkaloid form (base drug containing no additives such as hydrochloride in the crystalline form) is rarely used for medicinal purposes. Cocaine hydrochloride crystals or flakes come in Vs, A and 1 ounce bottles from the manufacturer and has a wholesale price of approximately 20 to 25 per ounce (100% pure). 

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]. 

Because of these two separate and largely inaccessible chiral centers there are, in theory, four distinct isomers of ibogaine which are difficult to resolve. When the term "synthetic" is used in regard to ibogaine in the scientific journals, it usually applies to the resynthesis of the parent alkaloid from the demethylated metabolite. For reference purposes, here are the finger print number from the infrared spectra For the free base IR (in cm-1) 741, 799, 830, 1037, 1111, 1148 mp 152-153 °C. For the hydrochloride salt IR (in cm-1) 638, 810, 832, 925, 1031, 1149 mp 299-300 °C (dec). 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Although there were some differences on the effects of temperature and pressure according to each particular compound, the free bases of hyoscyamine (1), scopolamine (2), and pseudoephedrine (6) were all found to be highly soluble in supercritical CO,. However, the hydrochloride salts of these compounds were scarcely extracted by pure CO, under any conditions employed. These results were consistent with preliminary evidence indicating that these alkaloids are not extracted from plant materials by pure CO,. This means that the alkaloids in living cells in the plant are not in the form of their free bases but rather as water-soluble salts in the cell vacuole [40]. Therefore, it was necessary to develop a procedure to enhance the solubilities of alkaloidal salts in CO,. 

Under optimized reaction conditions this two step synthesis for asymmetric preparation of /1-lactams is performed as follows. First, the organocatalyst 46 is added as a shuttle base to a solution of the acid chloride, 47, and the proton sponge , 49, at low temperature. Within a few minutes the soluble ketene and the hydrochloride salt, 49 HC1, as a white precipitate, are formed. Subsequently, the imino ester 44 is added to this solution at —78 °C, which results in the asymmetric formation of the /Mactam. Thus, the alkaloid 46 acts both as a dehydrohalogena-tion agent and as an organocatalyst for subsequent lactam formation [49, 52]. 

Extracts from skins of the neotropical frog Dendrobates tricolor from Ecuador have given the alkaloid 8-hydroxy-6-(2-methylhexylidene)azabicyclo[4.3.0]non-ane (4), the structure and absolute configuration of which have been determined by X-ray crystallography of the hydrochloride salt. This alkaloid is the first structurally defined member of the pumiliotoxin A class of dendrobatid alkaloids. Spectroscopic studies (m.s. and n.m.r.) have allowed the formulation of the... 

The improved synthesis of an antipsychotic pyrrolo[2,3-g]isoquinoline from an areca alkaloid shown in Scheme 3 <84JOC5109> began with a condensation of arecolone with dimethyl or diethyl malonate to give diketone (49). This diketone could be isolated and characterized as either the hydrochloride salt or the free base but was more conveniently subjected in crude form to Knorr... 

The benzylisoquinolines represent one of the largest group of plant alkaloids (146,147), and catecholic representatives occur in mammalian tissues and fluids. The best known is tetrahydropapaveroline, shown in Fig. 22 as the (5) enantiomer TIQ 75a. Racemic material is often referred to as THP (160,161). The synthesis of TIQ 75a as well as that of the plant alkaloid (5)-N -bisnorreticuline (77a) is shown in Fig. 22. (5)-Tetrahydropapaverine (74a), on treatment with concentrated hydroiodic acid at 125 C, afforded TIQ 75a, which was fully characterized as its hydrochloride (156). TIQ 77a, possibly an intermediate in the plant biosynthesis of (5)-norreticuline (78a) and derived TIQs, and possibly mammalian morphine as well, was prepared from the benzyl-protected TIQ 76a. Deblocking was achieved over Pd catalyst and hydrogen in the presence of hydrochloric acid, leading directly to the hydrochloride salt of TIQ 77a... 

Mecambroline was isolated from Meconopsis carnbrica Vig. (Papaver-aceae), and the elemental data indicated the value C18H17O3N. The alkaloid melts at 145°, and exhibits [aj +76° (in CHCI3). A hydrochloride salt was obtained (inp 264°-266°) as well as a picrate (mp 179°-180°). Color tests showed the presence of a methylenedioxy and a phenolic group. The UV-spectrum had 308 and 275 mp, (log e 4.0 and 4.2), with a shoulder at 269 mp (log e 4.1), typical of a 1,2,10-tri-substituted aporphine. 0-Methylation with diazomethane gave a base (mp 111°-112°) 6). 

Smoking the base alkaloid (as crack or freebase) and nasal insufflation of the hydrochloride salt are the most common routes of exposure in abuse. Intravenous injection and application of the hydrochloride salt to mucous membranes are also methods of abuse. In therapeutic use, a solution of hydrochloride salt is applied to mucous membranes. 

Concentration of 0.001% (or lower) to 1% of alkaloids can be performed. Alkaloids as salts (nitrates, hydrochlorides, hydrobromides, sulfates and acetates) were qualitatively separated at the cathode of an electrolytic cell. Of the several kinds of electrodes tested, aluminum as anode (wrapped in parchment) and a steel one as cathode were the most satisfactory. 

The specific rotations for the synthetic calystegine A, enantiomer hydrochlorides were +12.4° and -12.2s, respectively. Since the rotation of the hydrochloride salt of calystegine A3 has not been reported the synthesis does not unequivocally define the absolute configuration of the natural product, but the assumption was made that the alkaloid has the same absolute configuration as calystegine B i.e. IR,2S,3R,5R as shown in structure (14). 

The orchid alkaloid (- )-dendroprimine (327) was dealt with in Volume 28 of this treatise (7). The hydrochloride salt of an epimer, ( - )-8a-epidendroprimine (328), was recently synthesized from L-proline (372). 

It is important to use sulfuric acid at this point to ensure efficient extraction. The sulfate salt of the alkaloid is more soluble in water and less soluble in organic solvents than the hydrochloride salt. In the ADH of other alkenes the preferred system is sulfuric acid/diethyl ether. However stilbene diol Is only sparingly soluble in diethyl ether, which necessitates the use of ethyl acetate. Chlorinated hydrocarbon solvents should be avoided since both alkaloid salts have appreciable solubility in them. When diethyl ether is used as the organic phase, not all of the reaction mixture dissolves in it, but the material that remains undissolved is derived solely from 4-methylmorpholine. 

Morphine s poor aqueous solubility as the free alkaloid (about 1 5000) means that the drug is invariably used as the sulfate or hydrochloride salt, with which stable aqueous solutions (1 15 or better) for parenteral or oral use are readily prepared. In this respect, morphine is,... 

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