Yohimbine, 18-hydroxy

In the yohimbine group, reserpine Nfoxide has been found in the aerial parts of Melodinus balansae Baillon var. paucivenosus (S. Moore) Boiteau, and yohimbine, 18-hydroxy-yohimbine, reserpine, and rescinnamine in the stem bark of Rauwolfia cumminsii. Other extractions have resulted in the isolation of yohimbine, methyl reserpate, and (possibly) 18-hydroxy-yohimbine from the stem bark of R. vomitoria. ... 

The following yohimbine alkaloids, containing a methoxycarbonyl substituent at C-16 and a hydroxy group at C-17, were known when the previous review on that topic appeared in The Alkaloids (4) yohimbine (74), 0-yohimbine (75), corynanthine (76) (known also as rauhimbine), 1 l-methoxy-0-yohimbine (77), and 19,20-dehydroyohimbine (78). 

It should be noted that dialcohols 486, 487, and 488, obtained during the synthesis are stereoisomers of 18-hydroxy-a-yohimbine, which has an al-... 

A series of publications by Albright et al. report the investigation of methods for the oxidation of hydroxy groups in yohimbine-type alkaloids and the functionalization of yohimbone (305) at the C-18 position (293-297). 

Characteristic H-NMR (100 MHz) Data of Normal and Allo 18-Hydroxy yohimbines (254,255)... 

In general, it has been suggested that in the yohimbine series the planarity of the A, B, C and D rings is necessary for the affinity to a-adrenoceptors [57]. The selectivity between cti- and a2-adrenoceptor blocking activities is determined by the orientation of the carbomethoxy or the hydroxy group in ring E. 

Recent extractions440 of the leaves of Cinchona ledgeriana have resulted in the isolation of quinamine (previously observed), 3-ep/-quinamine, aricine, and a new alkaloid which may prove to be stereoisomeric with quinamine. 11-Hydroxy-pleiocarpamine occurs in Vinca erecta 4b and herbacine and herbaine in V. herbacea.44c Yohimbine appears to be the major alkaloid of the trunk bark of Pausinystalia macroceras, in which it occurs with four other alkaloids of this group.44d Pleiocarpamine occurs in association with nine alkaloids of the aspidospermine-eburnamine group in the stem and root bark of Hunteria elliottii (Stapf.) Pichon.44e... 

EtOH), were first isolated in 1872 and 1877, respectively (14). Quin-amine was observed to give indole color reactions (7, 15), and 2,3-dimethylindole was a result of zinc dust distillation of the alkaloid (15). With chromic acid (9), the quinuclidine carboxylic acid (III) was obtained, and with nitric acid 3,6,8-trinitro-4-hydroxyquinoline was isolated (15, 16). This quinoline is a consequence of fission of the indole and recyclization, with nitration preceding and following these steps [cf. ozonolysis of yohimbine to furnish a 2,3-disubstituted 4-hydroxy-quinoline (17)]. 

With the structure of quinamine firmly established, its other reactions can now be considered (Chart II), all of which proceed via VIII. When the alkaloid was refluxed with acetic anhydride or acetyl chloride, acetyl-apoquinamine (O-acetyl-d3- 14-cinchonamine, XII), picrate, mp 143° was obtained. The change may be formulated, quinamine VIII-XII, with the last step being a special case of a general reaction of hydroxy-indolenines (20). The analogous transformation can be realized very easily when 7-hydroxy-7/f-yohimbine methiodide (X) is boiled in methanol (21). 

Hydroxy-7//-yohimbine (294) derived from 7-acetoxy-7/7-yohimbine (277) on hydrolysis, underwent rearrangement to give yohimbine pseudoindoxyl (295) on treatment with 2 N potassium hydroxide in boiling methanol, whereas treatment with methanolic hydrochloric acid gave the hydrochloride of A -dehydroyohimbine (296) (Scheme 35). Treatment of 7-acetoxy-7//-ajmalicine (298) derived from ajmalicine (297) with methanolic sodium methoxide led to ajmalicine pseudoindoxyl (299). For structural determination of the pseudoindoxyl alkaloids by mass spectroscopy, Finch et al. 88) prepared 3-deuterio-,l4,I4-dideuterio-, 3,5,6-trideuterio-, and 3,14,14-trideuterioajmalicine pseudoindoxyls by the same methodology as above. 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

Serotonin is metabolized to bufotenin, and much of this is excreted in the urine as a glucuronide conjugate [56]. Vindoline and related alkaloids of Catharanthus roseus are extensively metabolized by mammals through the actions of esterases, peroxidases, and P-450 oxidases [57]. Oxidation of vindoline and vinblastine occurs in human serum, catalyzed by ceruloplasmin [58], The major metabolite of yohimbine is 11-hydroxyyohimbine, but the 10-hydroxy derivative is also produced [59], Strychnine injected into rats gives as its major metabolite its 21,22-epoxide, but other epoxidized and hydroxy derivatives are also prodced [60]. Harman is hydroxylated at C-6 by mice [61]. 

The structure and stereochemistry of the alkali-sensitive alkaloid powerine, which have previously eluded investigators, have now been established by the X-ray crystal structure analysis of its methanol solvate powerine proves to be 10-hydroxy-17-epi-a -yohimbine (105). 

Yohimbine 17a-Hydroxy-yohimban-16a-carboxylic acid methyl ester 354.44 g/mol(base) 390.90 g/mol (hydrochloride) C21H26N2O3 White crystalline powder odorless 226, 280,291 mn [120, 121]... 

Bark contains a number of alkaloids, the most important of which is yohimbine (reportedly up to 6% in crude bark) (17a-hydroxy-yohim-ban-16a-carboxylic acid methyl ester) also yohimbinine, a-yohimbane, yohimbenine, isoyohimbine (mesoyohimbine), dihydroyohimbine, corynantheine, and others. ... 

Szantay also utilized the Dieckmann cyclization strategy to prepare other 18-hydroxy yohimbine analogs (Scheme 3.46) (53). For example, Wadsworth-Emmons condensation of tetracyclic ketone 281 followed by hydrogenation provided diester 289. Dieckmann cyclization of 289 then afforded the epimeric pentacyclic esters 290 and 291. Treatment of 291 with sodium methoxide effected epimerization to the desired C(18)a methoxy epimer 290. Sodium... 

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