N. Ya. Grigorieva

Bio: N. Ya. Grigorieva is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Strobilurins & Stereoselectivity. The author has an hindex of 4, co-authored 16 publications receiving 52 citations.

Formal synthesis of strobilurins A and X

Abstract: Known synthetic precursors of strobilurins A and X, i.e., methyl (3Z,5E)-6-aryl-3-methylhexa-3,5-dienoates (aryl is phenyl, 4-methoxyphenyl), were synthesized by highly stereospecific reactions from 2-(2-tert-butyldimethylsilyloxyethyl)- and 2-[2-(4-methoxybenzyloxy)-ethyl]-5-arylpenta-2E,4E-dien-1-ols. These dienols were efficiently dehydroxylated to (1E,3Z)-4-methyl-6-(4-methoxybenzyloxy)hexa-1,3-dienylarenes with their subsequent demethoxyben-zylation to (3Z,5E)-6-aryl-3-methylhexa-3,5-dien-1-ols. The latter through the step of corresponding aryldienals and aryldienoic acids were transformed to the target methyl (3Z,5E)-6-aryl-3-methylhexa-3,5-dienoates, which completes a formal synthesis of strobilurins A and X. Configuration of the C=C bonds of the conjugated aryldiene system is preserved in the considered transformations by 95–97%.

Synthesis of Dolichyl Phosphates with a Fluorescent Label in the gamma-Isoprene Unit of the Chain

Abstract: Stereoselective synthesis of the dolichyl phosphate derivatives WT3C2S-OP and WT2C6,7S-OP* containing the 1-naphtylamino group in the gamma-isoprene unit of the chain was performed. The synthetic scheme includes directed aldol condensation to construct (E)-alfa,beta-disubstituted acroleins, their reductive amination with 1-aminonaphthalene, and phosphorylation of the resulting amino alcohols.

Highly stereoselective synthesis of 2,5-disubstituted (E, E)-penta-2,4-dienals

Abstract: A condensation of α,β-unsaturated aldehydes with O-protected 4-hydroxybutanal N-(tert-butyl)-imine has been exemplified for the first time using (E)-cinnamic and (E)-4-methoxycinnamic aldehydes. (E,E)-2,5-Disubstituted penta-2,4-dienals, which are key intermediates in the synthesis of strobilurins A and X, were prepared in good yields and close to 100% stereoselectivity.

Strobilurin biosynthesis in Basidiomycete fungi

Abstract: Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides However, molecular details of the biosynthesis of strobilurins have remained cryptic Here we report the sequence of genomes of two fungi that produce strobilurins and show that each contains a biosynthetic gene cluster, which encodes a highly reducing polyketide synthase with very unusual C-terminal hydrolase and methyltransferase domains Expression of stpks1 in Aspergillus oryzae leads to the production of prestrobilurin A when the fermentation is supplemented with a benzoyl coenzyme A (CoA) analogue This enables the discovery of a previously unobserved route to benzoyl CoA Reconstruction of the gene cluster in A oryzae leads to the formation of prestrobilurin A, and addition of the gene str9 encoding an FAD-dependent oxygenase leads to the key oxidative rearrangement responsible for the creation of the β-methoxyacrylate toxophore Finally, two methyltransferases are required to complete the synthesis

Synthesis and enzymatic phosphorylation of a photoactivatable dolichol analogue

Abstract: The synthesis of the photochemical probes 6 and 7 is described. These photoprobes are analogues of dolichol and dolichol phosphate, obligatory intermediates in the N-linked glycosylation pathway in the endoplasmic reticulum. The synthesis of 6 and 7 follows a new strategy. It involves the sequential alkylation of a monoterpenoid hydroxysulfonyl dianion with allyl chlorides. The photoreactive group, a 3-(trifluoromethyl)-3-aryldiazirine, was connected to the hydroxylated methyl group of the β-prenyl unit of the fully assembled polyprenyl chain. The photoactivatable dolichol analogue 6 is a substrate for dolichol kinase from yeast membranes, an essential enzyme involved in the N-linked glycosylation pathway.

Structural studies and mechanism of Saccharomyces cerevisiae dolichyl-phosphate-mannose synthase: insights into the initial step of synthesis of dolichyl-phosphate-linked oligosaccharide chains in membranes of endoplasmic reticulum.

Abstract: Dolichyl-phosphate-mannose (Dol-P-Man) synthase catalyzes the reversible formation of a key intermediate that is involved as a mannosyl donor in at least three different pathways for the synthesis of glycoconjugates important for eukaryotic development and viability. The enzyme is found associated with membranes of the endoplasmic reticulum (ER), where it transfers mannose from the water soluble cytoplasmic donor, guanosine 5'-diphosphate (GDP)-Man, to the membrane-bound, extremely hydrophobic, and long-chain polyisoprenoid acceptor, dolichyl-phosphate (Dol-P). The enzyme from Saccharomyces cerevisiae has been utilized to investigate the structure and activity of the protein and interactions of the enzyme with Dol-P and synthetic Dol-P analogs containing fluorescent probes. These interactions have been explored utilizing fluorescence resonance energy transfer (FRET) to establish intramolecular distances within the protein molecule as well as intermolecular distances to determine the localization of the active site and the hydrophobic substrate on the enzyme's surface. A three-dimensional (3D) model of the enzyme was produced with bound substrates, Dol-P, GDP-Man, and divalent cations to delineate the binding sites for these substrates as well as the catalytic site. The FRET analysis was used to characterize the functional properties of the enzyme and to evaluate its modeled structure. The data allowed for proposing a molecular mechanism of catalysis as an inverting mechanism of mannosyl residue transfer.