Diethyl phosphorocyanidate (DEPC): a versatile reagent for organic synthesis

Harusawa, Shinya; Shioiri, Takayuki

doi:10.1016/j.tet.2016.09.070

Cited by 20 publications

(7 citation statements)

References 300 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several strategies have utilized direct phosphorylation as part of both medicinal chemistry efforts and natural product synthesis. − A recent example by Kempson and co-workers at Bristol-Myers Squibb utilized direct phosphorylation in their scale-up synthesis of a potent GluN2B inhibitor and its prodrug . The initial attempts at direct phosphorylation of 4 using various phosphorylating agents, including H 3 PO 4 /P 2 O 5 , PCl 5 , H 3 PO 4 /Cl 3 CCN, and Na 4 P 2 O 7 , failed to deliver psilocybin in isolable quantity.…”

Section: Resultsmentioning

confidence: 99%

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

et al. 2020

View full text Add to dashboard Cite

A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The synthesis was designed to address several challenges first encountered with the scale-up of previously described literature procedures, which were not optimized for providing consistent yield and purity of products, atom economy, or being run in pilot plant-scale reactors. These challenges were addressed and circumvented with the design of the second-generation route, which featured an optimized cGMP large-scale Speeter–Anthony tryptamine synthesis to the intermediate psilocin with improved in-process control and impurity removal over the three steps. Psilocin was subsequently phosphorylated directly with phosphorous oxychloride for the first time, avoiding a tedious and poor atom economy benzyl-protecting group strategy common to all previously described methods for producing psilocybin. In this report, the challenges encountered in a 100 g scale first-generation literature-based synthesis are highlighted, followed by a detailed description of the newly developed second-generation synthesis to provide over one kilogram of high-purity psilocybin under cGMP.

show abstract

Section: Resultsmentioning

confidence: 99%

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

et al. 2020

View full text Add to dashboard Cite

show abstract

“…28 Subsequently, CPs have been utilized in organic synthesis as useful synthetic intermediates. 29 The treatment of a range of carbonyl compounds with diethyl phosphorocyanidate [(EtO)2P(O)CN, DEPC] 29a in the presence of a catalytic amount of lithium cyanide (LiCN) easily afforded CPs in THF. Use of 1.2 equiv.…”

Section: Tetrazole Fragmentation From Cpsmentioning

confidence: 99%

Generation of Alkylidene Carbenes through Tetrazole Fragmentation: Recent Advances and Applications in Organic Synthesis

Harusawa,

Yoneyama,

Usami

2024

Synthesis

Self Cite

View full text Add to dashboard Cite

Tetrazole-fragmentation under mild condition from 5-hydroxyalkyl-1H-tetrazoles (HATs) or cyanophosphates readily generates the corresponding alkylidene carbenes, which undergo [1,2]-rearrangements or [1,5]-C−H insertions to yield one-carbon homologous alkynes or five-membered unsaturated carbocycles, respectively. Furthermore, azido-HATs　and 2-cyanoazetidines afford propargylic and homopropargylic amines, respectively, via the [1,2]-rearrangements of the corresponding aminoalkyl alkylidene carbenes. These reactions have been successfully applied for the synthesis of various biofunctional molecules. This review summarizes the progress made in this methodology over the last decade.

show abstract

“…As described in the 1972 paper, 4 DPPA is a useful reagent for the amide synthesis by coupling of carboxylic acids with amines. 7 It is especially effective for the peptide synthesis with little or no epimerization during the fragment coupling in both the solution- and solid-phase methods, which was proved by the stringent Young racemization test using the coupling of benzoyl- l -Leu-OH with H-Gly-OEt, 4,5 a the epimerization test using the coupling of Cbz- l -Phe- l -Val-OH with H- l -Pro-OBu t , 8 and the Izumiya test on resin using the coupling of Boc-Gly- l -Ala-OH with H- l -Leu-polystyrene resin. 9…”

Section: Amides and Lactams Synthesismentioning

confidence: 99%

Cutting edge of diphenyl phosphorazidate (DPPA) as a synthetic reagent – A fifty-year odyssey

2022

Self Cite

View full text Add to dashboard Cite

show abstract

Diethyl phosphorocyanidate (DEPC): a versatile reagent for organic synthesis

Cited by 20 publications

References 300 publications

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

Generation of Alkylidene Carbenes through Tetrazole Fragmentation: Recent Advances and Applications in Organic Synthesis

Cutting edge of diphenyl phosphorazidate (DPPA) as a synthetic reagent – A fifty-year odyssey

Contact Info

Product

Resources

About