Aldol additions of dihydroxyacetone phosphate to N-Cbz-amino aldehydes catalyzed by L-fuculose-1-phosphate aldolase in emulsion systems: inversion of stereoselectivity as a function of the acceptor aldehyde

The potential of L-fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N-protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100 mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N-protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)-N-Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N-Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N-Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N-Cbz-glycinal and N-Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after C-C bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results.     

Stereoselective aldol additions of titanium enolates of N-acetyl-4-isopropyl-thiazolidinethione

The addition of chlorotitanium enolates of N-acetyl isopropyl thiazolidine-2-thione to aldehydes was investigated. The stereoselectivity of the aldol products was controlled by the number of equivalents of base added. The syn aldol product was obtained preferentially when 2 equiv of Lewis acid and 1 equiv of base were employed. The anti aldol product was obtained preferentially when 1 equiv of Lewis acid and 2 equiv of base were employed for unsaturated aldehydes. Unexpected results were found with hindered aldehydes when 2 equiv of base were employed.     

Stereoselective aldol additions catalyzed by dihydroxyacetone phosphate-dependent aldolases in emulsion systems: preparation and structural characterization of linear and cyclic iminopolyols from aminoaldehydes

The potential of dihydroxyacetone phosphate (DHAP)-dependent aldolases to catalyze stereoselective aldol additions is, in many instances, limited by the solubility of the acceptor aldehyde in aqueous/co-solvent mixtures. Herein, we demonstrate the efficiency of emulsion systems as reaction media for the class I fructose-1,6-bisphosphate aldolase (RAMA) and class II recombinant rhamnulose-1-phosphate aldolase from E. coli (RhuA)-catalyzed aldol addition between DHAP and N-benzyloxycarbonyl (N-Cbz) aminoaldehydes. The use of emulsions improved the RAMA-catalyzed aldol conversions by three to tenfold relative to those in conventional DMF/water mixtures. RhuA was more reactive than RAMA towards the N-Cbz aminoaldehydes regardless of the reaction medium. With (S)- or (R)-Cbz-alaninal, RAMA exhibited preference for the R enantiomer, while RhuA had no enantiomeric discrimination. The linear N-Cbz aminopolyols thus obtained were submitted to catalytic intramolecular reductive amination to afford the corresponding iminocyclitols. This reaction was diastereoselective in all cases examined; the face selectivity was controlled by the stereochemistry of the newly formed hydroxyl group originating from the aldehyde. Characterization of the resulting iminocyclitols allowed the assessment of the diastereoselectivity of the enzymatic aldol reactions with respect to the N-protected aminoaldehyde. RAMA formed single diastereoisomers from N-Cbz-glycinal and from both enantiomers of N-Cbz-alaninal, while 14 % of the epimeric product was observed from N-Cbz-3-aminopropanal. Diastereoselectivity from RhuA was lower than that observed from RAMA. Interestingly, a single diastereoisomer was formed from (S)-Cbz-alaninal, whereas only a 34 % diastereomeric excess was observed from its enantiomer (i.e., (R)-Cbz-alaninal).     

Synthesis of β-hydroxymalonates: the direct aldol addition of malonates to aldehydes in the presence of SiCl4 and i-Pr2EtN

The direct aldol addition of malonates to aromatic, hetero-aromatic and unsaturated aldehydes leading to β-hydroxymalonates is described. The stability of these products, the trimethyl silyl protection of the hydroxyl group as well as the role of both SiCl₄ and i-Pr₂EtN in attaining the final products are also discussed.     

Influence of alkyl length on properties of piezofluorochromic aggregation induced emission compounds derived from 9,10-bis[(N-alkylphenothiazin-3-yl)vinyl]anthracene

Three 9,10-bis[(N-alkylphenothiazin-3-yl)vinyl]anthracene derivatives with different propyl, hexyl, and dodecyl side chains (AnPh₃, AnPh₆, and AnPh₁₂) were synthesized and confirmed by standard spectroscopic methods. All of the compounds exhibited obvious aggregation induced emission (AIE) and piezofluorochromic (PFC) properties. The PFC behaviors were investigated and showed that proportional alkyl-length dependent relationship existed not only in the ground states of the compounds, but also in the melted states compared with the fumed states of the compounds. The PFC mechanism was explored and ascribed to the crystalline–amorphous phase transformation. More importantly, these derivatives showed reversible significant PFC properties and reproducibility in various states including fumed, ground, annealed, and melted states, making them promising stimuli-responsive and smart luminescent materials for pressure-sensors, information-recording, and light-emitting device applications.     

Influence of the side chain protecting group on the stereoselectivity of the 1,3-dipolar cycloaddition of d-talo-configured nitrones

Two new five-membered cyclic d-talo-configured nitrones were synthesized from d-mannose, and examined in 1,3-dipolar cycloadditions with vinyl acetate and vinylene carbonate. The stereoselectivity of the cycloadditions depends greatly on the protecting group of the vicinal diol attached to the nitrone C-5 carbon atom. Methyl protection resulted in limited syn/anti-selectivity, giving mixtures of the two isomeric exo-syn and exo-anti isoxazolidines in comparable amounts. On the other hand, the cyclohexylidene-substituted nitrone reacted more selectively in favour of the syn isomer. The difference in the diastereoselectivity was attributed to the specific spatial orientation of the nitrone C-5 substituent.