Alkaloid yohimbane alkaloids

Wender and Aube have independently described the use of the Bischler-Napieralski reaction in the synthesis of Yohimban alkaloids. Aube s approach involved the cyclization of indole 50 followed by reduction of the resulting dihydroisoquinoline... 

The iron-mediated [2 + 2 + 1]-cycloaddition to cyclopentadienones has been successfully applied to the synthesis of corannulene [24] and the yohimbane alkaloid ( )-demethoxycarbonyldihydrogambirtannine [25]. A [2 + 2 + l]-cydoaddition of an alkene, an alkyne and carbon monoxide mediated by pentacarbonyliron, related to the well-known Pauson-Khand reaction [26], has also been described to afford cyclopentenones [27]. 

In a previously described approach, a largely similar strategy was employed in order to generate enantio-selectively (—)-allo-yohimbane [84]. Yohimbane alkaloids such as reserpine and yohimbine were of long-standing interest from pharmacological and synthetic points of view, and the first enantio-selective (—)-alloyohimban synthesis was reported some time ago by Isobe et al. [88]. 

The process has been applied to the synthesis of derivatives of the yohimbane alkaloid... 

Sensitized photocyclization was used as a key step in the synthesis of the -ring functionalized alkaloid, yohimbane 267 (Scheme 63) [310]. 

The asymmetric total synthesis of rauwolfia alkaloids (-)-yohimbane and (-)-alloyohimbane was carried out by S.C. Bergmeier et al. by utilizing a novei aziridine-allylsilane cyclization and the Bischler-Napieralski isoquinoline synthesis as key steps.These alkaloids have a characteristic pentacyclic ring framework and exhibit a wide range of interesting biological activities such as antihypertensive and antipsychotic properties. 

Complex examples of the diene-alkyne [4+2] cycloaddition reaction have been illustrated in syntheses of a yohimban alkaloid and vitamin D analogs (Scheme 3-21). A representative procedure for the synthesis of a vitamin D analog is provided below. 

Indole Alkaloids Yohimbane, heteroyohimbane and oxindole groups. 

The known yohimbane alkaloids have been correlated with the key compounds on p. K9 by chemical and chiroptical means [1 ]. ORD/CD of the four yohimbane types [5]. 

The route employed to prepare indanone 51 involved the cycloaddition-hydrolysis-aldol sequence shown in Scheme 3.9. Accordingly, condensation of cyclopentenone 52 with ynamine 53 (84) afforded the bicyclic enamine 54 which was converted to indanones 51 and 55 by hydrolytic cyclobutane ring opening followed by intramolecular aldol condensation. Interestingly, treatment of 54 with aqueous formic acid yielded indanone 51 which has stereochemistry complementary to that at C(15) and C(20) in reserpine. In contrast, hydrolysis of this substance with aqueous hydrochloric acid afforded the trans-fused indanone 55. Subsequent to this work, the Ficini group found that esterification of 51 followed by photochemically induced addition of methanol afforded adduct 56 which has four of the reserpine stereocenters in place (23). While no further work on this problem has been reported, these preliminary investigations demonstrate a novel use of [2 -h 2] photocycloaddition chemistry in potential approaches to yohimbane alkaloid synthesis. 

Thus the critical synthetic 1,6-dihydropyridine precursor for the unique isoquinuclidine system of the iboga alkaloids, was generated by reduction of a pyridinium salt with sodium borohydride in base (137-140). Lithium aluminum hydride reduction of phenylisoquinolinium and indole-3-ethylisoquinolinium salts gave enamines, which could be cyclized to the skeletons found in norcoralydine (141) and the yohimbane-type alkaloids (142,143). 

Yohimbine (36) is a well-known and reasonably available alkaloid from Corynanthe yohimbe, inter alia. For this reason, and partly because of its intrinsic pharmacological activity (including reputed aphrodisiac activity), chemists have frequently studied its properties. Oppenauer oxidation is usually attended by saponification and decarboxylation in this series, and yohimbone (37) is the product. Wolf-Kischner reduction to yohimbane (38), followed by sodium hydride mediated alkylation, leads to the analgesic agent, mimbane (39). °... 

The quaternary alkaloid anhydroalstonatine (70), which has a completely aromatic yohimbane ring system, has been isolated from Alstonia venenata R.Br. (64). 

Epiallo Series. Among alkaloids containing the epiallo yohimbane skeleton, only 3-epi-a-yohimbine (105) was formerly known. In the past decade, four additional members of this alkaloid subgroup have been isolated, namely, quatematine (106) from Alstonia quaternata (84), venenatine (107) and its N-oxide (venoxidine) from Alstonia venenata R.Br. (79, 80, 82a, 85) and 16-epivenenatine (108) also from Alstonia venenata R.Br. (81). 

The previously known reserpine-type alkaloids (3) are shown below. They are reserpine (109), deserpidine (110), rescinnamine (111), veneserpine (112), pseudoreserpine (113), raunescine (114), rescidine (115), raugustine (116), and isoraunescine (117). It should be mentioned that all reserpine-type alkaloids are trisubstituted at ring E and that the substituents at C-16, C-17, and C-18 are all in equatorial positions on the epiallo yohimbane ring system existing predominantly... 

The conversion of indole alkaloids to oxindole derivatives has been studied extensively. Since this review does not deal with the literature of oxindole alkaloids, only the most important transformations of the alkaloids having indo-loquinolizine as well as yohimbane skeletons are to be mentioned. 

A series of publications appeared regarding the transformation of corynanthe-type alkaloids to yohimbane derivatives (285-287). The saponification of cory-nantheine (52) in methanol yielded a complex mixture of corynantheic acid (588), two C-16-epimer acetal acids (589), and demethoxycarbonylcory-nantheine (590). All four compounds upon hydrolysis in acid resulted in cory-... 

It has been shown that CD measurement is a proper tool to determine the absolute configuration of the C-3 stereo center in corynantheine and yohimbine alkaloids (300). The chiroptical properties of stereoisomeric yohimbanes and 17-ketoyohimbanes also have been studied. Cotton effects due to aromatic and ketone absorptions have been considered in terms of the appropriate sector and... 

Reserpine Reserpine is methyl ester 2a,ll-dimethoxy-3-(3,4,5-trimethoxybenzoyloxy)-yohimban-1-carboxylic acid (12.3.1). Reserpine is one of the alkaloids isolated from a perennial shrub of the Rauwolfia family [67-72]. It can also be synthesized [73-76]. 

As summarised here for the chemo-enzymatic approach of (—)-allo-yohimbane, synthon was once again the key lactone 1 (derived enzymatically from the above-mentioned meso-diacetate). Through condensation with tryptamine, a lactam was obtained which was then sequentially converted into (—)-allo-yohimban, indicating the high potential of this chemo-enzymatic approach for production of optically pure alkaloids of the terpenoid indoles. 

The numbering system for the alkaloids in this chapter is based on biogenetic relationships, i.e., an atom is assigned the same number as its supposed equivalent in yohimban,... 

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