Stereoselective allyl transfer to chiral α-methoxycarbaldehydes: A model study related to the C-9/C-15 fragment of geldanamycin

Horneff, Tony; Herdtweck, Eberhardt; Randoll, Sören; Bach, Thorsten

doi:10.1016/j.bmc.2006.05.056

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…The benzyl esters of α-hydroxy stearate 4 was synthesized [ 29 ] by heating α-hydroxystearic acid 3 , with benzyl bromide in presence of triethylamine, and catalytic amount of TBAI in toluene for 12 h in a yield of 56%. The benzyl ester of β-hydroxy stearate 9 is prepared in a similar way.…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of nucleolipids as possible activated precursors for oligomer formation via intramolecular catalysis: stability study and supramolecular organization

et al. 2014

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BackgroundFatty acid vesicles are an important part of protocell models currently studied. As protocells can be considered as pre-biological precursors of cells, the models try to contribute to a better understanding of the (cellular) origin of life and emphasize on 2 major aspects: compartmentalization and replication. It has been demonstrated that lipid-based membranes are amenable to growth and division (shell replication). Furthermore compartmentalization creates a unique micro-environment in which biomolecules can accumulate and reactions can occur. Pioneering research by Sugawara, Deamer, Luisi, Szostak and Rasmussen gave more insight in obtaining autocatalytic, self-replicating vesicles capable of containing and reproducing nucleic acid sequences (core replication). Linking both core and shell replication is a challenging feat requiring thorough understanding of membrane dynamics and (auto)catalytic systems. A possible solution may lie in a class of compounds called nucleolipids, who combine a nucleoside, nucleotide or nucleobase with a lipophilic moiety. Early contributions by the group of Yanagawa mentions the prebiotic significance (as a primitive helical template) arising from the supramolecular organization of these compounds. Further contributions, exploring the supramolecular scope regarding phospoliponucleosides (e.g. 5’-dioleylphosphatidyl derivatives of adenosine, uridine and cytidine) can be accounted to Baglioni, Luisi and Berti. This emerging field of amphiphiles is being investigated for surface behavior, supramolecular assembly and even drug ability.ResultsA series of α/β-hydroxy fatty acids and α-amino fatty acids, covalently bound to nucleoside-5′-monophosphates via a hydroxyl or amino group on the fatty acid was examined for spontaneous self-assembly in spherical aggregates and their stability towards intramolecular cleavage. Staining the resulting hydrophobic aggregates with BODIPY-dyes followed by fluorescent microscopy gave several distinct images of vesicles varying from small, isolated spheres to higher order aggregates and large, multimicrometer sized particles. Other observations include rod-like vesicle precursors. NMR was used to assess the stability of a representative sample of nucleolipids. 1D 31P NMR revealed that β-hydroxy fatty acids containing nucleotides were pH-stable while the α-analogs are acid labile. Degradation products identified by [1H-31P] heteroTOCSY revealed that phosphoesters are cleaved between sugar and phosphate, while phosphoramidates are also cleaved at the lipid-phosphate bond. For the latter compounds, the ratio between both degradation pathways is influenced by the nucleobase moiety. However no oligomerization of nucleotides was observed; nor the formation of 3′-5′-cyclic nucleotides, possible intermediates for oligonucleotide synthesis.ConclusionsThe nucleolipids with a deoxyribose sugar moiety form small or large vesicles, rod-like structures, vesicle aggregates or large vesicles. Some of these aggregates can be considered as intermediate forms in ve...

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Section: Resultsmentioning

confidence: 99%

Design and synthesis of nucleolipids as possible activated precursors for oligomer formation via intramolecular catalysis: stability study and supramolecular organization

et al. 2014

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“…The trans configuration for the C11-N1-C1-C2 part is typical. Two structural analogues of (II), with a methoxy group attached to atom C4, have been described (Horneff et al, 2006) and they have different stereochemistries at atoms C2 and C3 [(2S,3S) and (2R,3R)], as well as different conformations of the aliphatic chain.…”

Section: Commentmentioning

confidence: 99%

(2S,3S)-2,6-Dimethylheptane-1,3-diol, the oxygenated side chain of 22(S)-hydroxycholestrol, and its synthetic precursor (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2,6-dimethylheptanoyl]-1,3-oxazolidin-2-one

et al. 2013

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(2S,3S)-2,6-dimethylheptane-1,3-diol, C9H20O2, (I), was synthesized from the ketone (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2,6-dimethylheptanoyl]-1,3-oxazolidin-2-one, C19H27NO4, (II), containing C atoms of known chirality. In both structures, strong hydrogen bonds between the hydroxy groups form tape motifs. The contribution from weaker C-H···O hydrogen bonds is much more evident in the structure of (II), which furthermore contains an example of a direct short Osp(3)···Csp(2) contact that represents a usually unrecognized type of intermolecular interaction.

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“…The Western part 3, which evolved from the above-mentioned retrosynthetic considerations, seemed easily available from d-mannitol based on previous work. [12] The stereogenic center at C12 was retained from the chiral pool material upon oxidative cleavage and the stereogenic center at C14 was established by a directed hydrogenation. The stereogenic centers at C10 and C11 were formed by an enantioselective crotylation reaction.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Preparation of (E)‐Configured 1,2‐Disubstituted Propenes from Two Aldehydes by a Two‐Carbon Stitching Strategy: Convergent Synthesis of 18,21‐Diisopropyl‐Geldanamycin Hydroquinone and Its C7 Epimer

Hampel

Neubauer

Leeuwen

et al. 2012

Chemistry A European J

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The title compounds were synthesized in a longest sequence of 27 linear steps and with an overall yield of 2.9 and 3.9%. In the course of the synthesis, two aldehydes representing carbon fragments C1-C7 (Eastern fragment) and C9-C21 (Western fragment) were prepared from D-mannitol, each of which incorporated a key stereogenic center at the respective secondary methyl ether group (C6, C12) from the chiral pool material. The assembly of the two aldehydes was achieved employing α-chloroethyl magnesium chloride as a two-carbon building block. The carbenoid reagent was generated from α-chloroethyl para-tolylsulfoxide by sulfoxide-magnesium exchange and it added smoothly to the highly sensitive aldehyde of the Eastern fragment (C1-C7). Upon oxidation, an α-chloroethyl ketone was generated, which underwent a clean and high-yielding reductive SmI(2) -promoted addition to the other aldehyde fragment. Dehydration delivered the key double bond between C8 and C9 in an overall yield of 72% over four steps. The method was shown to be generally applicable to the racemization-free conversion of several aldehydes into the respective α-chloroethyl ketone (11 examples, 64-95%) and to the coupling protocol (5 examples, 66-90%). The further course of the geldanamycin hydroquinone synthesis included a diastereoselective reduction at C7 and the implementation of the amino group at C20. Since deprotection of the two isopropyl protecting groups could not be achieved in significant yields, the structure of 18,21-diisopropyl-geldanamycin hydroquinone was proven by its independent synthesis from the natural product.

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Stereoselective allyl transfer to chiral α-methoxycarbaldehydes: A model study related to the C-9/C-15 fragment of geldanamycin

Cited by 9 publications

References 44 publications

Design and synthesis of nucleolipids as possible activated precursors for oligomer formation via intramolecular catalysis: stability study and supramolecular organization

Design and synthesis of nucleolipids as possible activated precursors for oligomer formation via intramolecular catalysis: stability study and supramolecular organization

(2S,3S)-2,6-Dimethylheptane-1,3-diol, the oxygenated side chain of 22(S)-hydroxycholestrol, and its synthetic precursor (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2,6-dimethylheptanoyl]-1,3-oxazolidin-2-one

Stereoselective Preparation of (E)‐Configured 1,2‐Disubstituted Propenes from Two Aldehydes by a Two‐Carbon Stitching Strategy: Convergent Synthesis of 18,21‐Diisopropyl‐Geldanamycin Hydroquinone and Its C7 Epimer

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