Mild acetal cleavage using B-chlorocatecholborane in the synthesis of rearrangement-sensitive 2-arachidonoylglycerol

Roche, Michael; Madren, Seth; Tallent, Clyde; Carroll, F. Ivy; Seltzman, Herbert H.

doi:10.1016/j.tetlet.2012.04.039

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…Upon omitting the silane, we observed a partial cleavage of the 4,6-O-benzylidene moiety (Table 3, entry 5), presumably resulting from nucleophilic attack of chloride on the PhBCl 2 -activated acetal, as already observed with Bchlorocatecholborane. 78 This last experiment established that it is important to add Et 3 SiH prior to PhBCl 2 to avoid such side reaction. Taken together, these results confirm that, when using the PhBCl 2 /Et 3 SiH reagent system in CH 2 Cl 2 , the kinetics of the reductive opening reaction is much faster than both the chlorosilane reduction/hydroboration cascade and 4,6-O-benzylidene cleavage.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…To further explore the minimum requirements for the reaction, we decreased the amount of PhBCl 2 to 1.1 equiv; however, the reaction did not proceed to completion, and we recovered 43% of starting material 1 along with 54% of compound 3a (Table , entry 4). Upon omitting the silane, we observed a partial cleavage of the 4,6- O -benzylidene moiety (Table , entry 5), presumably resulting from nucleophilic attack of chloride on the PhBCl 2 -activated acetal, as already observed with B-chlorocatecholborane . This last experiment established that it is important to add Et 3 SiH prior to PhBCl 2 to avoid such side reaction.…”

Section: Resultsmentioning

confidence: 99%

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Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them

et al. 2022

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Arylidene acetals are widely used protecting groups, because of not only the high regioselectivity of their introduction but also the possibility of performing further regioselective reductive opening in the presence of a hydride donor and an acid catalyst. In this context, the Et3SiH/PhBCl2 system presents several advantages: silanes are efficient, environmentally benign, and user-friendly hydride donors, while PhBCl2 opens the way to unique regioselectivity with regard to all other Brønsted or Lewis acids used with silanes. This system has been extensively used by several groups, and we have demonstrated its high regioselectivity in the reductive opening of 4,6- and 2,4-O-p-methoxybenzylidene moieties in protected disaccharides. Surprisingly, its use on 4,6-O-benzylidene-containing substrates 1 and 2 led to unreproducible yields due to the unexpected formation of several side products. Their characterizations allowed us to identify different pitfalls potentially affecting the outcome of reductive opening of arylidenes with the Et3SiH/PhBCl2 reagent system: alkene hydroboration, azide reduction, and/or Lewis acid-promoted cleavage of the arylidene. With this knowledge, we optimized reproducible and high-yielding reaction conditions that secure and extend the scope of the Et3SiH/PhBCl2 system as a reagent for the regioselective opening of arylidenes in complex and multifunctional molecules.

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Section: ■ Results and Discussionmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them

et al. 2022

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“…To date, 2-AG is synthesized by either chemical [16][17][18][19] or chemoenzymatic methods To date, 2-AG is synthesized by either chemical [16][17][18][19] or chemoenzymatic methods [20][21][22][23]. The chemical methods described for the synthesis of 2-AG are based on the same procedure: acylation of suitable 1,3-protected glycerol, or glycidol, precursors with an activated arachidonic acid derivative, followed by deprotection and separation of the isomeric arachidonoylglycerols.…”

Section: -Arachidonoylglycerol (2-agmentioning

confidence: 99%

“…B-Chlorocatecholborane was also used for acetal cleavage of cis-arachidonoylbenzylidene glycerol [19] that demonstrated the mildness of the reagent on an especially sensitive transformation while also affording an improved quality of product of current interest. Nevertheless, the silyl [24] and benzyl [17,19] protected glycerol approaches experienced at least 5% rearrangement, demonstrating the sensitivity of this molecule to deblocking conditions and identifying it as a probe of the mildness of reaction conditions.…”

Section: -Arachidonoylglycerol (2-agmentioning

confidence: 99%

2-Arachidonoylglycerol Synthesis: Facile and Handy Enzymatic Method That Allows to Avoid Isomerization

Ottria

Casati²,

Rota³

et al. 2022

Molecules

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A simple and practical synthesis of 2-arachidonoyl glycerol (2-AG), an endogenous agonist for cannabinoid receptors, based on a two-step enzymatic process and a chemical coupling, was achieved with a good yield and negligible amount of the isomerization product 1-AG. Commercial preparation of immobilized lipase from Mucor miehei (MML) was selected as the most suitable enzyme to catalyze the efficient protection of glycerol using vinyl benzoate as an acyl transfer reagent in tetrahydrofuran. The same enzyme was used to remove the protective groups in positions 1 and 3. Owing to the mild neutral conditions and easy suitability of the method, 2-AG was obtained without any isomerization to the more stable 1-AG and air oxidation of acid chain. The synthetic method proposed here allows us to easily obtain 2-AG from the protected precursor in a one-step reaction without purification requirement.

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“…Although some researchers have successfully synthesized pure 2-AG by chemical methods (Roche et al, 2012;Cartoni et al, 2004), 2-AG is extremely unstable. The ratio of 1-AG and 2-AG at equilibrium state is 9:1 (Andrews et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel method for the synthesis of symmetrical triacylglycerols by enzymatic transesterification

Tang

Wang

Huang

et al. 2015

Bioresource Technology

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Mild acetal cleavage using B-chlorocatecholborane in the synthesis of rearrangement-sensitive 2-arachidonoylglycerol

Cited by 5 publications

References 13 publications

Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them

Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them

2-Arachidonoylglycerol Synthesis: Facile and Handy Enzymatic Method That Allows to Avoid Isomerization

A novel method for the synthesis of symmetrical triacylglycerols by enzymatic transesterification

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