Chirality pairing recognition, a unique reaction forming spiral alkaloids from amino acids stereoselectively in one-pot

Bai, Bing; Li, Dashan; Huang, Sheng‐Zhuo; Ren, Jie; Zhu, Hua‐Jie

doi:10.1007/s13659-012-0003-6

Cited by 7 publications

(1 citation statement)

References 8 publications

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“…The TME's amine reacts with the first ketone group of 2,3-diketobutane initiating the Pictet-Spengler reaction to afford a six-membered ring moiety. [24,25] This is followed by a second TME reacting with the keto group via another Pictet-Spengler sequence to form compounds 3 (racemates 3(1) and 3(2)) and 4 (racemates (4(1) and 4(2)) [26,27] (Scheme 1, Items 2-6, Figures S1-S7 and Tables S1-S10 in SM) using various methods. [28][29][30][31] Since the two compounds polarities were quite close, it is difficult to obtain their very purity in a high yield.…”

Section: Theoretical Investigation Of Chiral Amplification Without An...mentioning

confidence: 99%

Amplification of Enantiomeric Excess without Any Chiral Source in Prebiotic Case

Zhu¹,

Jia²,

Li³

et al. 2023

Preprint

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A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.

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Section: Theoretical Investigation Of Chiral Amplification Without An...mentioning

confidence: 99%

Amplification of Enantiomeric Excess without Any Chiral Source in Prebiotic Case

Zhu¹,

Jia²,

Li³

et al. 2023

Preprint

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Chirality

2015

Organic Stereochemistry

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A Diversity‐Oriented Approach to Spiroindolines: Post‐Ugi Gold‐Catalyzed Diastereoselective Domino Cyclization

et al. 2012

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Gold-catalyzed carbocyclization and heteroannulation strategies have recently attracted much attention owing to the selective and efficient activation of the CC bond towards a wide range of nucleophiles that these methods provide. [1] Domino approaches involving gold-catalysis lead to complex heterocyclic compounds under exceedingly mild reaction conditions. [2] Although gold-catalyzed approaches are rising to prominence, they suffer in terms of diversity and procedural length. Multistep sequences are usually required for assembling the starting material for cyclization. We have recently reported a concise route to indoloazocines by a sequential Ugi/gold-catalyzed intramolecular hydroarylation approach. [3] Inspired by these findings and as a result of our continued synthetic interest in the indole core, [4] multicomponent reactions [5] and transition metal-catalysis, [6] we have developed a post-Ugi gold-catalyzed domino cyclization method to generate spiroindolines.The Ugi four-component reaction (4-CR) [7] of indole-3carboxaldehyde (1 a) with p-methoxybenzyl amine (2 a), 2-butynoic acid (3 a) and tert-butyl isonitrile (4 a) in methanol at 50 8C gave Ugi-adduct 5 a in 71 % yield. When this was treated with 5 mol % of Au[PPh 3 ]OTf (OTf = trifluoromethanesulfonate) in CDCl 3 at RT, the expected outcome of the reaction was indoloazepinone 6 a' through an endo-dig cyclization [1m,n, 3] followed by rearrangement (Scheme 1). Surprisingly, an exo-dig cyclization followed by intramolecular trapping of the spiro intermediate occurred instead, resulting in the diastereoselective formation of tetracyclic spiroindoline 6 a in 61 % yield (Scheme 1).This observation was remarkable, as the attack on the a-position of an alkyne conjugated with an amide is rare, and trapping of the spiro intermediate by a sterically hindered tert-butyl amide is rather unexpected, as was the diastereoselectivity observed. Spiroindolines [8] are prominent molecular motifs that are frequently encountered among the large family of alkaloids; for example, it is present in communesines [8,9] and perophoramidines [8,10] (Figure 1), which display distinct pharmacological properties. [8][9][10] These fused polycyclic systems, which feature quaternary stereocenters, present a nontrivial challenge for organic chemists to develop synthetic approaches. [11]

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Chirality pairing recognition, a unique reaction forming spiral alkaloids from amino acids stereoselectively in one-pot

Abstract: Abstract:A novel chirality pairing recognition was found between D-and L-amino acid derivatives. Novel spiral alkaloids formed in the recognition reaction. Possible mechanism was proposed for the stereoselective and chemoselective reactions.

Cited by 7 publications

References 8 publications

Amplification of Enantiomeric Excess without Any Chiral Source in Prebiotic Case

Amplification of Enantiomeric Excess without Any Chiral Source in Prebiotic Case

Chirality

A Diversity‐Oriented Approach to Spiroindolines: Post‐Ugi Gold‐Catalyzed Diastereoselective Domino Cyclization

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