Thiol group of L-cysteine or GSH could act as a
nucleophile to react with the alkylation agent, namely [alpha], [beta]-unsaturated ketone group in the D-ring of diterpenoids.
In this experiment we used benzene as a solvent; p-toluenesulfonic acid (TsOH), which has strong acidity but low nucleophilicity, as a catalyst; and acetylacetone, ethyl acetoacetate, and diethyl malonate as
nucleophiles. As a result, when acetylacetone and ethyl acetoacetate were used, the expected 6-substituted indoles (21, 22) were obtained.
The redder the area is, the higher the electron density is susceptible to electrophilic attack and the bluer the area is, the lower the electron density is that could easily bind with a
nucleophile.
The other signals observed in both spectra were very similar to those observed in the isomer spectra, though, in this case both the hydroxyl groups, at positon 1 or 3 carbon may serve as
nucleophiles for intramolecular substitution reaction.
We measured the distance of
nucleophile attack; the distance between [O.sub.[gamma]] of S162 and the carbon atom of carbonyl group in pNPC12 is 3.1 [Angstrom] of WT-pNPC12 complex; however, in I100F-pNPC12 complex, the distance is 3.7 [Angstrom] (Figure 6).
However, the [S.sub.N]2(C) pathway competes at neutral pH (8) and with a "soft"
nucleophile such as [I.sup.-] or [Br.sup.-], and also in a cetyltrimethylammonium (CTA) micellar system.
(16) They proposed that the
nucleophile would approach at 107[degrees] away from the carbonyl oxygen, where the HHPA axial carbonyl carbon was sterically shielded by the 3 and 5 protons of the ring.
It is interesting to note that [alpha], [beta]-unsaturated ketones epoxidize under strongly alkaline conditions by peroxides [14] and in these cases peroxide reacts as a
nucleophile. It is also known that t-BuOOH is ineffective toward enones in the presence of [Et.sub.3]N [15].
Essentially every compound targeted and prepared is new because of the difficulty inherent in traditional and other methods, and the syntheses represent another group of reactions where an anionic
nucleophile is condensed with an anionic electrophile.
This is because using 0.5 M (NH4)2SO4 is insufficient to provide necessary SO4 2-to form superacid; while using the high concentration (1.5 M), NH3 the decomposition product of NH4 is
nucleophile inhibiting the formation of Bronsted acid sites.
Nitrosocarbonyls are in fact short-living species, just 180 [micro]s as reported by Cohen and coworkers [20] and, if not instantly trapped, can add the excess NMO to give the intermediate 7i that evolves to add nucleophilic species which can be present in the reaction mixtures even in small amounts to afford N-methylmorfoline, [N.sub.2]O, and the adduct between the benzoyl group and the
nucleophile Nu (in case of water, benzoic acid) [21].
The nucleophilic attack by a nitrogen
nucleophile, such as hydrazine, hydrazide and hydroxylamine, in carbonyl-containing functionalities, such as an aldehyde or ketone, has been an extensively explored orthogonal approach for protein labeling.