Yohimbine-type alkaloids synthesis

Two important books on the biogenesis of indole alkaloids have been published (5, 6), therefore we do not intend to cover the literature of the biogenesis of corynantheine- and yohimbine-type alkaloids. Our chapter begins with the structure elucidation of the alkaloids isolated during the past two decades and proceeds with the synthesis, transformation, as well as spectroscopy of the alkaloids in question. 

The second approach (224-226) employs O-methylhexadehydroyohimbine (420), prepared from spiroindeno-2-(l -tetrahydro-0-carboline)-l-onederivative 416 by photolysis and subsequent reduction, as the key intermediate. The side product (418) of the photolysis was also utilized for the preparation of 420 via subsequent phosphoryl chloride treatment and sodium borohydride reduction. Birch reduction of 420 resulted in enol ether 421, which could be transformed to 15,16-didehydroyohimbinone (410), prepared previously by Szantay et al. (74, 221) as a universal precursor of the synthesis of yohimbine-type alkaloids. 

Waldmann used (R) and (5>aminoacid methyl esters and chiral amines as chiral auxiliaries in analogous aza-Diels-Alder reactions with cyclodienes.111 The diastereoselectivity of these reactions ranged from moderate to excellent and the open-chain dienes reacted similarly. Recently, the aza-Diels-Alder reaction was used by Waldmann in the asymmetric synthesis of highly functionalized tetracyclic indole derivatives (Eq. 12.45), which is useful for the synthesis of yohimbine- and reserpine-type alkaloids.112... 

So far, reductive photocyclization has been successfully applied to the synthesis of yohimbine-type compounds (54), benzo[/]quinolines, and ergot alkaloids including lysergic acid (55-57) (Scheme 19). 

The hydrogen abstraction, in this instance, presumably occurs at the P-carbon of the enone (139). The resultant biradical ring closes to afford the observed products. The ic-ic excited triplet state is involved in the conversion of the enone (141) into the spiroketone (142). The reaction again involves hydrogen abstraction by the ft-carbon followed by cyclization within the biradical. Photocyclization of enamides such as (143) has led to a new synthetic approach to the yohimbine anreserpine type alkaloids. " The photocyclization of the enone (144) provides a route for the synthesis of 3.10-dimethoxyprotoberberines. ... 

Yohimbine (obsolete synonyms johimbine, quebra-chine, aphrodine). C21H26N2O3, Mk 3S4.4S. The parent indole alkaloid of the yohimbine type occurring in nature as the (-t-l-form, the racemate is accessible by synthesis. Other, naturally occurring stereoisomers of Y. have been isolated a-Y. (rauwolscine, corynanthidine, isoyohimbine, mesoyohimbine, 16/3,17ct, 20a-Y.), allo-Y. (16a,17a,20a-Y), 3-epi-a-Y. (isorauhim-bine), /3-Y. (amsonine), and corynanthine (rauhimbine, 16, 17a-Y). 

The transformation of indole into corresponding oxindole alkaloids has been possible for some time now the reverse sequence has been achieved. The type of 2,3-seco-intermediate (47) arrived at by total synthesis above has been pro-duced " and then cyclized, in both heteroyohimbine (Scheme 12) and yohimbine... 

Intramolecular acylations of the Bischler-Napieralski type have been used as crucial steps in the synthesis of indole alkaloids of the yohimbine class <94JCS(Pl)299, 94TL1071>. Also, the aluminum chloride-catalysed reaction of the indolosuccinic anhydride (46) gave the bridged cyclic product (47) rather than the cyclopentanone (49), presiunably because the reaction involves initial acylation at C-3 and reaction via the less strained intermediate is favored. Formation of the cyclopentanone (49) can be achieved using the polyphosphate ester cyclodehydration of the modified intermediate (48) (Scheme 13) <90JCS(Pi)2487>. 

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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