Heteroyohimbine group, synthesis

In connection with partial synthesis in the ring-E-seco alkaloids and the heteroyohimbine group, several Nb-oxides have been prepared. Dihydrocory-nantheine, on oxidation with m-chloroperbenzoic acid, affords two epimeric Nb-oxides whereas its pseudo isomer, hirsutine, gives only one. Desmethyl-hirsuteine Nb-oxide (91), when treated with trifluoroacetic anhydride in methylene chloride, undergoes the Polonovski reaction reduction of the product by means of buffered sodium cyanoborohydride then affords a mixture of desmethylcorynantheine (92), 3-i5o-rauniticine (93), and akuammigine (94) (Scheme 12). Clearly, formation of an immonium ion can occur in the Polonovski reaction either towards C-3 [- (95)], which results in the ultimate epimeriza-... 

During the past two decades a great number of papers have been published on the isolation, structure elucidation, synthesis and transformation, biogenesis, chemotaxonomy, and pharmacology of indole alkaloids. In this chapter we summarize the new results that appeared from 1968 to mid 1984 for the cory-nantheine-yohimbine group of monoterpene indole alkaloids with greater emphasis on their chemistry, excluding the related oxindoles and heteroyohimbines. 

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... 

To show the way in which one of the piperidine isomers was synthesized and how each was utilized to make heteroyohimbine alkaloids, the full synthesis of ( )-tetrahydroalstonine (44a) and ( )-akuammigine (44b) is detailed in Scheme 11. As well as the effective dehydrogenation of the ethyl group, notable in the sequence is the intramolecular oxymercuration, (45) — (46), which in the cis-series leads, by kinetic control, only to the 19 -isomer. Also of interest is the absence, apparently, of inside isomers (such as have been reported in other similar cyclizations, see below) in the closure of the C-ring, i.e. (47) — (44). 

Intramolecular enolate addition to an -fluoroacrylate was a key step in the synthesis of a heteroyohimbine indole alkaloid containing a 2,3-dihydrofuran moiety <01SL1125>. An endo ring closure at the s/j-hybridized carbon center of an allenyl unit to form a 2,3-dihydrofuran as shown below was observed when the allenyl sulfoxide containing a primary 6-hydroxy group was allowed to react with potassium rert-butoxide <01OL3385>. 

In the first slide I summarized what I am going to talk today, the list of target indole alkaloids. My talk consists of two parts, the first part is on the synthesis of yohimbine and its group and the second part on the synthesis of corynantheine and heteroyohimbine types of alkaloids. 

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