Yohimbine alkaloids

Similarly to the corynantheine-type alkaloids, yohimbines could also be divided into four groups according to the relative configurations of the stereo centers C-3, C-15, and C-20. 

The C=C double bond in 4-methylcou-marin has been hydrogenated at a Hg cathode in the presence of alkaloids with 17% ee [388]. By systematic variation of pH, supporting electrolyte, working potential, substrate, and alkaloid (yohimbine) concentration, the enantioselectivity has been increased to 67% ee. A mechanism supported by electroanalytical data and preparative scale electrolysis is proposed. 

Selective a -adrenoblockers such as the alkaloid yohimbin have limited chnical use. 

Since the adsorption of plant metabolite onto adsorbent is a strong function of pH, the effect of pH upon the adsorption capadty of a plant metabolite should be investigated to understand and quantify product adsorption. The pH dependence of indole alkaloids, yohimbine and ajmalicine, and berberine onto XAD-7 has been reported [ 16,20]. As a model system, XAD-7 was examined to quantify berberine adsorption, especially in terms of pH and concentration dependence, which were used for the in situ berberine separation in Thalictrum ru-gosum cultures [19, 20]. Dependence of berberine adsorption on pH and concentration was investigated as shown in Fig. 4. Equilibrium ratio (Q/C), an affinity of berberine, could be calculated by Eq. (1) ... 

The combinatorial decoration or derivatization of existing natural products is a popular method for library creation. Among targets for such exercises are the alkaloids yohimbine and scopolamine, terpenoids and steroids, and the heterocyclic peptide antibiotic GE-2270A (Figure 11). In the latter case, combinatorial variation was instrumental in the discovery of a developmental candidate now in clinical trials at Vicuron. Pfizer, the world s largest pharmaceutical company, recently acquired Vicuron for the sum of 1.9 billion, a mark of approval for natural product-based combinatorial chemistry. 

Examples of ai-blockers include compounds of diverse structures, such as the synthetic heterocyclics prazosin, indoramin, phentolamine the ergot alkaloids crgotamine and dil droergotamine and the haloalkylamine irreversible alkylators, e.g. phenoxybenzamine. Examples of antagonists relatively selective for a2-receptors over a,-receptors, are the natural indolealkylamine alkaloid yohimbine and its diastereoisomer rauwoisdnc (though they also have affinity for 5-HT receptors). However, mariy of the tt -blockers (especially prazosin) also have some affinity at the a2-adrenoceptor site. 

The indole alkaloids provide an even richer source of biogenetic interrelationships. Thus, condensation of tryptamine and dihydroxyphenyl-acetadehyde (or equivalent precursors) under conditions similar to those already described gives a tetrahydro-harman derivative (diagram 26 cf. 336,338). Further condensation of this with formaldehyde (cf. 335) (which may be biogenetically derived from, say, serine or glycine) gives the same basic skeleton as in the alkaloid yohimbine. 

Systematic structure activity relationships (SARs) around the scaffold of the natural alkaloid yohimbine led to the discovery of 1,2,3,4-tetrahydro-p-carboline (THpC) derivatives that have been shown to be very potent and highly selective 5HT2b receptor antagonists. Of particular interest are 1-substituted-THpC compounds (1 to 4) that were selected for further development (Figure 6.1). 

Most information regarding the action of alkaloids relates to the alpha 2 receptor, where the indole alkaloids yohimbine and its isomer, rauwolscine, bind with high affinity and block the receptor [187, 191]. Dihydrocorynantheine, an indole alkaloid of similar structure preferentially binds to the alpha 1 receptor, as do some aporphines [192,... 

Monoterpenoid Alkaloids.— Yohimbine-Corynantheine-Heteroyohimbine and Related Oxindoles) Group. Holeinine ° from Bleekeria vitiensis ° (and Ochrosia sandwicensis) is isoreserpiline metho-salt the former source contains, inter alia, 10,11 -dimethoxyalstonine. ... 

The standard dose is 5.0 to 6.0 mg of the contained alkaloid (yohimbine), three to four times daily (Martindale and Reynolds 1996 Osol and Farrar 1955). 

Examples of this technique are described for artificial receptors for the alkaloid yohimbine binding peptides obtained from a phage display library [57], for the steroid libraries related to lla-hydroxyprogesterone [58], corticosterone [58] (reported in Fig. 12), and cortisol [59]. A molecularly imprinted polymer working as a synthetic receptor for a series of chiral benzodiazepines [47], artificial receptors for the tricyclic antidepressant drug nortriptyline—obtained by covalent and noncovalent molecular imprinting and studied by capillary liquid chromatography with a simulated combinatorial library [60,61]—were also examined. 

Thus, the remaining steps to the alkaloids yohimbine and alloyo-himbine gave us no problem, thus furnished a novel and practical synthesis of both alkaloids as summarized in the scheme. 

The alkaloid yohimbine eliminates i molecule of water when it combines with acids to form salts. ... 

One of the earliest reports on the combinatorial modification of natural products described the derivatization of the Rauwolfia indole alkaloids yohimbine and rauwolscine (Figure 11.58). The... 

Bark may contain up to 6 % total alkaloids, of which 10-15 % is yohimbine [120]. Concentrations of yohimbine in commercial products ranged from less than 0.1 to 489 parts per million (ppm) compared with 7,089 ppm in the authentic material. The alkaloid yohimbine also is obtained from Aspidosperma quebracho-bianco and Rauwolfia serpentina [121]. Its interest outside the African continent was first recorded in Germany, where yohimbine, the main alkaloid of the drug and also known as aphrodine, quebrachine, or corynine, was isolated for the first time by Spiegel in 1896 [130]. Recent advancements in the development of yohimbe-based... 

Corynanthe yohimbe (Pausinystalia yohimbe Rubiaceae) is a evergreen tree native to the southern part of Africa and to Cameroon, Nigeria, and Zaire. Occasionally it is planted in tropical countries. Its bark coontains a total of 0.3%-1.5% alkaloids. The well known indole alkaloid yohimbine has been obtained as a major alkaloid from the bark. The bark has been used traditionally as an aphrodisiac by African natives. Yohimbine hydrochloride is used as an adrenergic blocker for humans. 

Traditional Medicine. Bark reportedly used as an aphrodisiac for centuries, though little evidence support claims that it has an effect on sexual desire or performance. The majority of pharmacological data are on the alkaloid yohimbine, rather than the erode drug. 

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