Structure and chemistry of a zwitterionic amine–aldehyde adduct

Kirby, Anthony J.; Komarov, Igor V.; Bilenko, Vitaliy A.; Davies, John E.; Rawson, Jeremy M.

doi:10.1039/b206639d

Cited by 26 publications

(28 citation statements)

References 8 publications

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“…This outcome is in line with the unusually strong proximity effect, responsible for the peculiar reactivity. In fact, the carbonyl group in saraine A was unable to be reduced by NaBH 4 [5] and the zwitterionic form could not to be trapped by reaction with iodomethane, which is similar to the reactivity of the synthetic compound by Kirby et al [11] In the latter case, the zwitterioniclike form could be trapped with Meerwein's reagent (trimethyloxonium tetrafluoroborate), known as a very strong methylating agent. Similarly, by treatment of saraines A -C with the same reagent we obtained methyl derivatives 10-12 (Scheme 2), whereas iodomethane were unreactive.…”

Section: Structural Analysis and Chemical Reactivitymentioning

confidence: 77%

“…This is also in line with the report that Hdonor solvents like methanol are very effective in forming the protonated form bearing the quaternary ammonium unit. [11] ESI-MS analysis provided new experimental evidence to support the structure of these metabolites. The spectrum recorded in the positive ion mode through direct injection into the source of a CH 3 + .…”

Section: Structural Analysis and Chemical Reactivitymentioning

confidence: 86%

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New Structural Insights into Saraines A, B, and C, Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai

et al. 2011

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The structural peculiarity of saraines A, B and C, wherein a zwitterionic‐like form is present due to the coordination of a nitrogen atom to the C‐2 aldehyde by a strong proximity effect, has been further extended by experimental and theoretical evidences. They include the detection of [2M + H]+ clusters in electrospray ionization mass spectrometry in the positive ion mode of a water/acetonitrile solution, whereas only signals corresponding to [M + H]+ ions are detectable after addition of trifluoroacetic acid to the same solution. The zwitterionic form can be trapped to give O‐methyl derivatives only by reaction with a strong alkylating agent such as Meerwein's reagent. DFT calculations carried out on the core structural model suggest that the nucleophilic N‐1 atom in the minimized conformation is at a suitable distance from the carbonyl group and also defines an approach angle in good agreement with the Bürgi–Dunitz model. Antibacterial and hemolytic activities and inhibition of acetylcholinesterase (AChE) assays have been evaluated for saraines A–C in comparison to those of saraines 1–3 and isosaraine 1, all the metabolites isolated from the sponge Reniera (Haliclona) sarai collected in the Northern Adriatic sea.

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Section: Structural Analysis and Chemical Reactivitymentioning

confidence: 77%

Section: Structural Analysis and Chemical Reactivitymentioning

confidence: 86%

New Structural Insights into Saraines A, B, and C, Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai

et al. 2011

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“…We reported recently that the amino aldehyde 1 exists predominantly in polar solvents, and exclusively in the crystal, as the CO addition structure 2 [7]. The thermodynamically stable adamantane unit provides an energy sink deep enough to accommodate the high-energy tetrahedral zwitterion.…”

mentioning

confidence: 99%

“…Not only is 2 a single compound, it is observed in the crystal −under one particular set of conditions, in the crystal in the presence of one molecule of water of crystallization× [7]. Calculations suggest that it would exist in the ring-opened form in the gas phase, and NMR evidence is consistent with increasing amounts of NÀC bond-formation in more polar solvents [7]. So the detailed structure is expected to depend on the environment ± in solution on the polarity of the solvent, and in the crystal on the presence or absence of water of crystallisation.…”

mentioning

confidence: 99%

“…We are not unmindful of an important caveat that we have articulated as follows: −for most purposes evidence based on a single structure is basically anecdotal× [2]. Not only is 2 a single compound, it is observed in the crystal −under one particular set of conditions, in the crystal in the presence of one molecule of water of crystallization× [7]. Calculations suggest that it would exist in the ring-opened form in the gas phase, and NMR evidence is consistent with increasing amounts of NÀC bond-formation in more polar solvents [7].…”

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confidence: 99%

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Structural Correlations for Nucleophilic Addition to the CO Group: The Solvation Angle

Davies¹,

Kirby²,

Komarov

2003

Helvetica Chimica Acta

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Dedicated to Professor Jack D. Dunitz on the occasion of his 80th birthdayWe report some new observations in B¸rgiÀDunitz territory ± structureÀstructure correlations for the addition of N nucleophiles to the CO group. The amino aldehyde 1 exists predominantly in polar solvents, and exclusively in the crystal, as the carbonyl-addition structure 2, but appears to demand hydrogen-bonding solvation as part of the process. In terms of CÀO bond lengthening, the new system lies somewhere nearly halfway between an amino aldehyde and a stable quaternary ammonium aminal: we present the structure 2 ¥ Me of the N ÀCÀOMe derivative of 2 as an example. We have investigated the effects on the cyclisation equilibrium in this system of hydration, which is important, and of the degree of methylation of the azaadamantane skeleton, which ± unexpectedly ± is not. In terms of the reverse process, i.e., breaking the CÀN bond: in each case, the bond is lengthened by (n (O) Às* (CÀN) ) electron-pair donation from the O-atom (the generalised anomeric effect, as in 2 ¥ Me 6 3, below) [4]. This effect is strongest when the O-atom is negatively charged, reduced by hydrogen-bonding, and minimised by alkylation.Introduction. ± The work of the Dunitz school has had a major and lasting impact on the way we think about ± and teach ± some very fundamental chemistry. The idea that crystal structures ± to a first approximation static representations of stable molecules ± can provide important insights into reactivity is by now so familiar, and supported by so much evidence, that it no longer seems counterintuitive. We accept, for example, that the B¸rgiÀDunitz angle defines the preferred trajectory of approach of a nucleophile as it adds to a CO group, and, thus, contains fundamental information about the geometry of the orbital interactions involved in bond formation [1].We have learned also that crystal structure correlations can illustrate, or even reveal, quite subtle conformational and basic stereoelectronic preferences in suitable systems [2]. If the relevant data set is large enough, it is generally a reasonable assumption that intramolecular and packing forces specific to individual structures will −average out×, so that small molecules at least adopt the same conformation in the crystal and in solution. For example, the conformational preferences determined by the anomeric effect are observed in detail in series of crystal structures [2]; making the leaving group XO À better drives the conformations of benzylic systems ArCH(Me)-ÀOX towards the conformation required for optimal pÀs* overlap and subsequent cleavage [3], and the directionality of H-bonding to a CO group can be related to the shape of the electron density in the nonbonding orbitals of sp

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Total Synthesis of (−)‐Sarain A

2006

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Structure and chemistry of a zwitterionic amine–aldehyde adduct

Abstract: The zwitterionic tetrahedral addition product 1 is the preferred form of the amino-aldehyde 4 in polar solvents and in the crystal, where a molecule of water controls the structure.

Cited by 26 publications

References 8 publications

New Structural Insights into Saraines A, B, and C, Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai

New Structural Insights into Saraines A, B, and C, Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai

Structural Correlations for Nucleophilic Addition to the CO Group: The Solvation Angle

Total Synthesis of (−)‐Sarain A

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