Yohimbine precursor

The tricyclic lactone, 163, was also transformed to a yohimbine precursor by Polniaszek and Stevens (Scheme 3.26). Treatment of 163 with methoxide induced a double bond migration which was followed by Michael addition of methoxide. Subsequent oxidation and thermolysis effected selenoxide elimination to provide 166. Ozonolysis of the double bond followed by reduction yielded a mixture of bis-hemiacetals which were reduced with triethylsilane in trifluoroacetic acid to provide the tricyclic pyran 167. Reduction of the lactone and tritylation of the primary alcohol function afforded 168 which was subjected to xanthate ester elimination to give the enol ether 169. Oxymercuration-reduction and detritylation afforded the methylpyranoside... 

D-tubocurarine from Chondrodendron tomentosum Ruiz et Pav. and Rauvolfia serpentina Benth. et Kurz and horse radish peroxidase 3 mg/ml, which prevent the peroxide formation, block the fruit formation as a whole, while yohimbine and gaillardine inhibit the seed formation. Neostigmine stimulates the fruit and seed yield, although its precursor physostigmine has no significant effect (Roshchina and Melnikova, 1998). 

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. 

Pseudoakuammicine is the first racemic base to be discovered in the strychnine-yohimbine series of alkaloids, and the question of its origin naturally arises. The only stage in the extraction of Picralima seeds during which racemization of akuammicine might have occurred involved prolonged percolation with hot methanol however, as already discussed, akuammicine is not racemized under these conditions but suffers a more extensive decomposition. In any event, such a racemization would necessarily involve fission of the 3,7 and 15,16 bonds, followed by a nonspecific resynthesis, which is considered to be a very unlikely possibility. It was therefore suggested that, in the plant, pseudoakuammicine is produced by a nonspecific biosynthesis this would accord with its formation from a tryptophan-phenylalanine precursor, but not from an optically pure prephenic acid derivative (40). 

The indole alkaloids provide an even richer source of biogenetic interrelationships. Thus, condensation of tryptamine and dihydroxyphenyl-acetadehyde (or equivalent precursors) under conditions similar to those already described gives a tetrahydro-harman derivative (diagram 26 cf. 336,338). Further condensation of this with formaldehyde (cf. 335) (which may be biogenetically derived from, say, serine or glycine) gives the same basic skeleton as in the alkaloid yohimbine. 

Two routes to the pentacyclic yohimbine skeleton carrying ester groups at C-16 have been described. Dieckman cyclization " (Scheme 8) of (37), a synthetic precursor of (38), leads to a major product in which closure occurs in the desired sense, in contrast to a comparable reaction on (38). 

An alternative to the aromatic amino acids hypothesis is one which invokes their proximate precursor, viz. a hydrated prephenic acid in which the potential ring E of yohimbine is already in a reduced state and has in addition the carboxyl. An important conclusion arising out of this theory was the prediction of a uniform stereochemistry in indole alkaloids of Type I at the carbon equivalent C-15 of yohimbine. This hypothetical biogenesis—the prephenic acid theory is Ulustrated in Chart 2.3. 

In the present state of biogenetic theory, it cannot be assumed that the combination of the ten carbon precursor and tryptophan must always lead to a basic compound. The recent isolation of certain aspidosperma alkaloids which owe their basicity and therefore the reason they were isolated to the indoline nitrogen may mean inter alia that the analogous yohimbine derivative (lactam carbonyl group at C-5 in Chart 2.3) is also a natural product. 

As shown in Chart 5.1, a wide variety of alkaloid skeleta are derivable from Type I precursor and tryptamine by further ring closures. It is worth pointing out that in so far as they have been investigated, they all have had the same stereochemistry for the carbon equivalent to C-15 of yohimbine. In this chapter, certain tetrahydro-j8-carboline alkaloids, viz., the yohimbines, their ring E seco equivalents and ring E oxygen heterocycles will be discussed since they show much chemistry in common. Over the years most of their degradation products have been synthesized, they have been interrelated, their absolute stereochemistries derived, and some have been synthesized. For these reasons they have become valuable reference compounds. 

Eric N. Jacobsen of Harvard University has devised a family of catalysts for the enantioselective Pictet-Spengler reaction of tryptamine 21. He has now (Organic Lett. 2008, 10, 745) used this approach to prepare the triene 22 in 94% ee. The Diels-Alder cyclization of 22 proceeded with high diastereocontrol to give 23, the immediate precursor of (-)-yohimbine 24. 

The Diels-Alder reaction is yet another cycloaddition process which has been used extensively to construct the D and E-ring system of the yohimbines. In synthetic organic chemistry, both intermolecular (85-90) and intramolecular (91-93) [4 -h 2] cycloadditions have served as powerful tools for the construction of functionalized 6 membered rings. The intermolecular version of this reaction has been used to generate appropriately substituted cyclohexane precursors of reserpine (24-30). Moreover, the intramolecular variant of the... 

The primary alcohol was converted to methyl ester 171 which was hydrolyzed to hemiacetal 172, the ring closed form of aldehydo-alcohol 173 and a precursor of 3-epialloyohimbine (9). While the syntheses of the target molecules were not completed, the work of Polniaszek and Stevens illustrates how Cope rearrangements can be used effectively to generate cis-fused DE-ring precursors of the yohimbine alkaloids. 

Chatteijee has synthesized a variety of yohimbine alkaloids utilizing 3-isochromanone derivatives as DE-ring precursors (Scheme 3.89) (140). For... 

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