Oxindoles double

Alkaloid Solvent —NH- Ester and oxindole Double carbonyl bond Others... 

An unusual case of addition of a carbanion to an unconjugated carbon-carbon double bond is shown in Scheme 47a. The subsequent transfer of the amide group is also noteworthy (80CC1042). The intramolecular addition of a carbanion to an aryne is a more widely established process. Such reactions have been applied to the synthesis of indoles (Scheme 47b) (75CC745> and oxindoles (Scheme 47c) (63JOC1,80JA3646). 

Their most detailed investigations focused on the Heck cyclization of iodide 18.1c to form oxindole 17.3a (Scheme 8G.18) [38a,b]. A chiral-amplification study [47] established that the catalytically active species is a monomeric Pd-BINAP complex, a conclusion also corroborated by NMR studies by Amatore and co-workers [42d,43], In addition, two possibilities for the enantioselective step of the neutral pathway were easily eliminated [38a], Oxidative addition was precluded as the enantioselective step, because iodides cyclize with very different enantioselectivities in the presence of Ag(I) salts. A scenario where migratory insertion is reversible and [l-hydridc elimination is the enantioselective step was also ruled out, because this is not consistent with the dependence of enantioselectivity on the geometry of the double bond of the cyclization precursor. 

The partial synthesis70 of macroline (136) from normacusine B (140) was inspired by its postulated biosynthesis from a sarpagine-type precursor. Normacusine B (140), prepared by a previously published route from perivine, was protected at the primary alcohol group and then methylated on Na. Direct epoxidation of the product (141) failed however, osmylation gave the desired diol together with the related oxindole obtained by simultaneous oxidation of the indole double-bond, followed by rearrangement. Conversion of these diols into the related epoxides gave a mixture of (142) and (143), from which the desired epoxide (142) could be separated satisfactorily by fractional crystallization. 

Aside from the oxindole fragment of the molecule, this formulation was largely speculative the presence of an A-methyl group and a terminal double bond was well founded, but there was no incontrovert-... 

The constitution (I) for gelsemine is clearly incapable of explaining all these experimental data, but those which were subsequently proposed were also inadequate in one or more respects. On the basis of the bromina-tion experiments, and the probable proximity of the double bond to the oxindole group, the alternatives Va and Vb were advanced (66, 71). In both formulas, the position of the ether link was not specified, although... 

The condensation products from the reactions of isatins with cyanoacetates can be reduced at the carbon-carbon double bond with Zn dust in HC1 or by hydrogenation with Pd/C. Subsequent decarboxylation can be achieved by refluxing in 2-ethoxy ethanol. Further reduction of the nitrile yields an ethylamine oxindole (Scheme 98). 

The main tool compounds available for mechanistic research at present are EHNA 15 (sub-micromolar inhibitor of PDE2A, the first selective inhibitor of PDE2A described in the literature [156]), BAY 607550 16 (depending on the construct a nanomolar to sub-nanomolar inhibitor of PDE2A, structurally related to EHNA [153]), and the chemically distinct oxindole 17 (double-digit nanomolar inhibitor of PDE2A with good selectivity [105]) as shown in Fig. 8. 

The oxindole structure (XXIX) of this alkaloid was established by consideration of a combination of spectral evidence. Thus, its mass spectrum confirmed the analytically found molecular formula of C23H30N2O6 bj showing a molecular ion at m/e 430. Further, it exhibited a strong peak at m/e 225 due to the fragment e, two mass units higher than the corresponding ion in the mass spectra of mitraphylline and carapanau-bine which have a C-16, C-17 double bond. Other peaks in the spectrum are also shifted by the appropriate number of mass units expected for... 

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