Pseudoyohimbine

Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

Bohlmann et al. (118-121) observed that an infrared absorption band between 2700-2800 cm is characteristic of a piperidine derivative possessing at least two axial carbon-hydrogen bonds in antiperiplanar position to the free-electron pair on the nitrogen atom. The possibility of forming an enamine by dehydrogenation can be determined by this test. Compounds which do not fulfill this condition cannot usually be dehydrogenated (50, 122,123). Thus, for example, yohimbine can be dehydrogenated by mercuric acetate,whereas reserpine or pseudoyohimbine do not react (124). The quinolizidine (125) enamines (Scheme 4), l-azabicyclo(4,3,0)-nonane, l-azabicyclo(5,3,0)decane, l-azabicyclo(5,4,0)undecane, and l-azabicyclo(5,5,0)dodecane have been prepared in this manner (112,126). 

Pseudo Series. Besides the previously known pseudoyohimbine (88), there is only one additional alkaloid found in Rauwolfia capuroni Mgf. (68) that belongs to the pseudo series, namely, 11-methoxypseudoyohimbine (89). 

The first total synthesis of D/E-trans annellated yohimbines, e.g., ( )-yohim-bine (74) and ( )-pseudoyohimbine (88), was published in preliminary form by van Tamelen and co-workers (218) in 1958, while full details (219) appeared only in 1969. Key building block 393, prepared from butadiene and p-quinone, was condensed with tryptamine, yielding unsaturated amide 394, which was subsequently transformed to dialdehyde derivative 396. Cyclization of the latter resulted in pseudoyohimbane 397. Final substitution of ring E was achieved via pyrolysis, oxidation, and esterification steps. As a result of the reaction sequence, ( )-pseudoyohimbine was obtained, from which ( )-yohimbine could be prepared via C-3 epimerization. 

Reduction of imino ether 540 with sodium borohydride led to 2,3-seco-2,3-dihydroyohimbine (413), which could be tecyclized by mercuric acetate oxidation, followed by acid treatment, yielding yohimbine (74) and pseudoyohimbine (88) (271-272). 

The preparation and stereochemistry of some indole alkaloid N-oxides was studied by Sakai and co-workers (276). The N-oxidation of yohimbine (74) with m-chloroperbenzoic acid under mild reaction conditions led to two isomeric N-oxides (556 and 557) in a ratio of 10 1. MCPBA oxidation of pseudoyohimbine (88) afforded a single product (558). 

Reaction of yohimbine (74) with cyanogen bromide in ethanol-chloroform afforded an isomeric mixture of (3/ )- and (3S)-ethoxy-3,4-secocyanamide derivative (562 and 563, respectively) (277, 278). It was found that the relative amounts of 562 and 563 depend on the molar ratio of ethanol to the substrate applied during the reaction. Stereospecific ring closures of 562 and 563 with hot acetic acid yielded yohimbine and pseudoyohimbine (88), respectively. 

The oxidation probably involves a mercurated complex through the electron pair on nitrogen followed by a concerted removal of a proton from the a-carbon and then cleavage of the mercury-nitrogen bond. The suggestion that a trans elimination occurs is reinforced by the evidence that yohimbine can be hydrogenated by mercuric acetate, whereas reserpine methyl reserpate, deserpine, or pseudoyohimbine does not react [122]. 

The acid-catalysed epimerization reaction often contributes to the change of conformation that alters the sterical shape of a compound. This may have a severe effect on pharmacological properties as with reserpine (1) and isoreserpine (2). The same seems to apply to the C-3 epimers yohimbine (78) and pseudoyohimbine (79). Yohimbine (78) blocks ai-receptors, whereas pseudoyohimbine (79) has little affinity for this... 

Pseudoyohimbine has been found much less potent than yohimbine to inhibit the stimulation-evoked release of labelled GABA [58]. Some early studies on the stereochemical and pharmacological properties of yohimbine and its isomers have been reviewed [59]. 

The four major stereochemical types of yohimbine alkaloids are illustrated by yohimbine (normal) [368], pseudoyohimbine (pseudo) [369], cr-yohimbine (alio) [370], and 3-ep/-a-yohimbine (epiallo) [371]. Of particular diagnostic importance are the C(3), C(6), and C(15) shifts... 

Another convenient method for the preparation of enamines involves the dehydrogenation of saturated bases with mercuric acetate. A trans- 1,2-elimination probably occurs. The electron pair on the nitrogen atom and the hydrogen atom to be eliminated must both be axial. Thus, for example, yohimbine (24) can be dehydrogenated by mercuric acetate, whereas reserpine (25) or pseudoyohimbine (26) do... 

This isomer (LXI) was obtained from corynanthine by the procedure used to obtain pseudoyohimbine from yohimbine (14). 

For example, yohimbine containing an a-oriented axial hydrogen at C3 can be dehydrogenated by mercuric acetate, whereas reserpine or pseudoyohimbine with /1-oriented hydrogen does not react305,309-312. Sparteine (83) is oxidized to a mixture of isomers A5,11-didehydrosparteine (84) and A5-dehydrosparteine (85). The other two stereoisomers of sparteine, i.e. a-isosparteine (86) and jS-isosparteine (87) dehydrogenate to 84290,313-315. 

A detailed study of the previously uninvestigated U. borneensis was also carried out. The major alkaloids were the tetracyclic oxindoles isorhynchophylline, rhynchophylline, isocorynoxeine, and corynoxeine accompanied by minor yohimbine alkaloids, pseudoyohimbine, alloyohimbine and 3-epi-P-yohimbine (81). The unique and predominant occurrence... 

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