Synthesis of deuterated fatty acids to investigate the biosynthetic pathway of disparlure, the sex pheromone of the Gypsy Moth, <i>Lymantria dispar</i>

Abad, José Luı́s; Fabriás, Gemma; Camps, Francisco

doi:10.1007/s11745-004-1244-0

Cited by 11 publications

(9 citation statements)

References 13 publications

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“…In the first step, commercially available 1,12-dodecanediol was successfully monobrominated according to a protocol reported earlier by Greaves et al The monobrominated 12-bromo-1-dodecanol could be isolated in a 77% yield in a reaction using a large excess of HBr in cyclohexane. The yield is well within the 65–92% range commonly reported in the literature. − To access compound 1 , the temporary protection of the hydroxyl group as a TBDMS-ether was required. The TBDMS-ether was chosen because of its stability toward basic conditions and the mild and selective installation and deprotection protocols available in the literature .…”

Section: Results and Discussionsupporting

confidence: 74%

The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

et al. 2021

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The tear film lipid layer (TFLL) that covers the ocular surface contains several unique lipid classes, including O -acyl-ω-hydroxy fatty acids, type I-St diesters, and type II diesters. While the TFLL represents a unique biological barrier that plays a central role in stabilizing the entire tear film, little is known about the properties and roles of individual lipid species. This is because their isolation from tear samples in sufficient quantities is a tedious task. To provide access to these species in their pure form, and to shed light on their properties, we here report a general strategy for the synthesis and structural characterization of these lipid classes. In addition, we study the organization and behavior of the lipids at the air–tear interface. Through these studies, new insights on the relationship between structural features, such as number of double bonds and the chain length, and film properties, such as spreading and evaporation resistance, were uncovered.

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Section: Results and Discussionsupporting

confidence: 74%

The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

et al. 2021

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“…The latter usually require one or more CÀC coupling steps, most frequently by alkylating deprotonated primary alkynes or thioketals with primary alkyl halides. [12] Both procedures, however, generally involve the application of the toxic additive HMPA, [13] which is to be strictly avoided nowadays. In some cases, selective deuteration with D 2 by using Wilkinson's catalyst is also feasible.…”

Section: Resultsmentioning

confidence: 99%

Influence of Substrate Dideuteration on the Reaction of the Bifunctional Heme Enzyme Psi Factor Producing Oxygenase A (PpoA)

et al. 2011

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PpoA is a bifunctional enzyme that catalyzes the dioxygenation of unsaturated C18 fatty acids. The products of this reaction are termed psi factors and have been shown to play a crucial role in conferring a balance between sexual and asexual spore development as well as production of secondary metabolites in the fungus Aspergillus nidulans. Studies on the reaction mechanism revealed that PpoA uses two different heme domains to catalyze two subsequent reactions. Initially, the fatty acid substrate is dioxygenated at C8, yielding an 8-hydroperoxy fatty acid at the N-terminal domain. This reaction is catalyzed by a peroxidase/dioxygenase-type domain that exhibits many similarities to prostaglandin H2 synthases and involves a stereospecific homolytic hydrogen abstraction from C8 of the substrate. The C terminus harbors a heme thiolate P450 domain in which rearrangement of the 8-hydroperoxide to the final product, a 5,8-dihydroxy fatty acid, takes place. To obtain further information about the intrinsic kinetics and reaction mechanism of PpoA, we synthesized C5-dideutero- and C8-dideutero-oleic acid by a novel protocol that offers a straightforward synthesis without employing the toxic additive hexamethylphosphoramide (HMPA) during CC coupling reactions or mercury salts upon thioketal deprotection. These deuterated fatty acids were then employed for kinetic analysis under multiple-turnover conditions. The results indicate that the hydrogen abstraction at C8 is the rate-determining step of the overall reaction because we observed a KIE (V(H) /V(D) ) of ∼33 at substrate saturation that suggests extensive nuclear tunneling contributions for hydrogen transfer. Deuteration of the substrate at C5, however, had little effect on V(H) /V(D) but resulted in a different product pattern presumably due to an altered lifetime and partitioning of a reaction intermediate.

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“…To a mixture of 6.45 g (30 mmol) of alkynol 2 and 0.93 g (1 mmol) of Wilkinson catalyst, 4 200 mL of degassed benzene was added under argon atmosphere to afford a reddish solution. The system was purged by a combination of vacuum and passing a D 2 stream throughout it, then D 2 atmosphere was kept from a balloon and the solution was stirred for 48 h. The mixture was filtered through a bed of Celite and the solvent evaporated.…”

Section: Deuteration Of Alkynolmentioning

confidence: 99%

Substrate-Dependent Stereochemical Course of the (Z)-13-Desaturation Catalyzed by the Processionary Moth Multifunctional Desaturase

2007

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The stereochemical course of the Delta13 desaturation involved in the biosynthesis of Thaumetopoea pityocampa sex pheromone was studied using stereotopically labeled and tagged palmitic acids as metabolic probes. In the synthetic pathway, a functionalized acetylene common synthon was used for introducing the four deuterium tags. Further coupling of the tetradeuterated synthon to the appropriated alkynol and a double chemoenzymatic strategy to resolve the alcohol functionality allowed one to obtain the enantiomerically enriched probes used in the mechanistic studies. Mass spectrometric analyses of extracts from tissues cultured with each probe revealed that removal of the C13 and C14 hydrogens in 11-hexadecynoate and (Z)-11-hexadecenoate are pro-(R)- and pro-(S)-specific syn-dehydrogenation processes, respectively. This finding constitutes the first example in the literature of an enzymatic (Z)-desaturation exhibiting a substrate-dependent stereochemical course.

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Synthesis of deuterated fatty acids to investigate the biosynthetic pathway of disparlure, the sex pheromone of the Gypsy Moth, Lymantria dispar

Cited by 11 publications

References 13 publications

The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

Influence of Substrate Dideuteration on the Reaction of the Bifunctional Heme Enzyme Psi Factor Producing Oxygenase A (PpoA)

Substrate-Dependent Stereochemical Course of the (Z)-13-Desaturation Catalyzed by the Processionary Moth Multifunctional Desaturase

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