Heteroyohimbine alkaloid

The above structure/activity tendency is seen again in heteroyohimbine alkaloids. Tetrahydroalstonine (83) exhibits considerable selectivity towards presynaptic ct2-adrenoceptors but raubasine (ajmalicine) (84)... 

Brown s one-pot synthesis54" affords mainly (19S)-heteroyohimbine alkaloids (e.g. tetrahydroalstonine) by a kinetically controlled process involving preferential formation of an ( )-alkene (61 ) from the initially formed dienamine... 

A 400 MHz n.m.r. study640 of the eight parent heteroyohimbine alkaloids has permitted the chemical shifts of all the protons to be established. Carbon-13 n.m.r. data have also been recorded646 for the alio- and epiallo-oxindole alkaloids containing a heterocyclic ring E. 

Over seven-hundred references are concerned with the isolation and chemistry of alkaloids, and approximately one-third of these are devoted to synthesis and biosynthesis. It is perhaps in these areas that the most notable research is to be found. Although it is probably invidious to attempt the exercise, a personal selection of highlights would include new results on the biosynthesis of quinoliz-idine alkaloids (p. 4), the first synthesis of an eleven-membered macrocyclic pyrrolizidine diester (p. 49), the synthesis of Poranthera alkaloids (p. 68), and, in the indole field, the synthesis of tryptoquivalines G and L (p. 152), of a chiral intermediate in the construction of heteroyohimbine alkaloids (p. 167), and of a catharanthine intermediate, using palladium catalysts (p. 186). 

Ajmalicine (=raubasine) is a heteroyohimbine alkaloid with positive effects on postischemic hypoxia and cerebral protection [25-27] and has anti-hypertensive, sedative and oxygen supplying activities in brain tissue. It can be enzymatically... 

Bayer-Villager oxidation of the cyclopentanone derivative (442 R = chiral auxiliary) with MCPA gives the saturated pyranopyridone derivative (443) which has been used in the total synthesis of the heteroyohimbine alkaloid, 3-isorauniticine (444) <9iJA966o>. 

Mitraphylline and rhynchophylline undergo characteristic fragmentation processes on electron impact, hence their mass spectra are markedly different from those of the tetrahydro-/3-carboline alkaloids in general, and of the heteroyohimbine alkaloids (e.g., ajmalicine) in particular. Consequently, the mass spectra of the oxindole alkaloids promise to be very valuable in the structural elucidation of new members of this subgroup the structure of one such base, carapanaubine, a constituent of Aspidosperma carapanauba M. Pichon, has already been elucidated by this method, and the structure deduced has subsequently been confirmed by partial synthesis from isoreserpiline (82). 

The heteroyohimbine alkaloids can be effectively hydroxylated at the (aromatic) C-10 and C-11 positions. For example ajmalcine (51) is 10-hydroxy lated in 92% yield by Curminghamella elegans (ATCC 9245) and tetrahydroalstonine (52) is 11-hydroxylated in 72% yield by a plant-derived ntold. This latto transformation is particularly difficult to achieve by chemical methods. 

A similar Polonovski reaction with the N-oxide of desmethylhirsuleine (3) leads to two heteroyohimbine alkaloids, 3-isorauniticine (4) and akuammigine (5), and desmethylcorynantheine (6), formed by epimerization of 3. ... 

Steric cours of hydrogen transfer during enzymatic formation of 3a-heteroyohimbine alkaloids. Biochemistry 1983 22 3448-3452. 112. 

A more economical use of 40, in terms of carbon atoms and chiral centers, was devised to produce the heteroyohimbine alkaloid ajmalicine and its 19-epimer [54]. As shown in Scheme 11.13, deoxygenation of 40 at C6 followed by oxidative cleavage of the vinyl group gave the corresponding aldehyde 43, which was equilibrated to the equatorial isomer 44. Subsequent reaction with tryptamine gave the piperidinone 45. Bisher-Napieralsky cyclization provided the alkaloid skeleton, which was elaborated to ajmalicine 46. 

In connection with the development of a partial synthesis of heteroyohimbine alkaloids from corynantheine (109), thereby obviating a possibly troublesome... 

In continuation of his biomimetic syntheses of heteroyohimbine alkaloids Brown" has succeeded in converting secologanin tetra-acetate (117) into elenolic acid (118), and in completing the synthesis of ajmalicine (80) essentially by the route published" earlier (Scheme 14). Contrary to the previous workers, who apparently isolated only ajmalicine. Brown eta/." obtained ajmalicine (80), 19-epiajmalicine (119) and tetrahydroalstonine (120). Since one of the lactams (121) afforded only 19-epiajmalicine (119) and in the general reaction sequence the proportion of (80), (119), and (120) in the final product depended on the length of time allowed for Schiff base formation rather than on the ratio of isomers present in the methyl elenolate [ester of (118)], it is apparent that interconversion of the imines (122) via the equilibria shown in Scheme 14 is responsible for the non-stereospecificity of the synthesis. 

In a gas chromatographic study of the effect of methoxy substitution and configuration of heteroyohimbine alkaloids on the retention times on a 1 % SE-30 packed column, Beckett... 

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

The heteroyohimbine alkaloids and their oxindole counterparts form a large group of compounds that provide an ideal exercise in conformational analysis the oxindole bases, which contain in C-7 an additional asymmetric center, have been particularly thoroughly studied. The oxindole alkaloids that occur in Mitragyna and related genera have previously been discussed in Volumes VIII and X of this series and by 1967 the complete conformations of most of these alkaloids had been elucidated. The known facts concerning the stereochemistry of these alkaloids at that time have been summarized by Shamma et al. (46, 47), and the stereochemistry of the uncarines-A-F has also been... 

Akuammigine and (+ )-tetrahydroalstonine have also been synthesized by a novel route as part of a large program of synthesis directed toward the Cinchona and heteroyohimbine alkaloids 27, 28). This synthesis is particularly noteworthy for the original method used for the construction of ring E. The first major objective in this approach... 

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