233277-99-1Relevant articles and documents
Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors
Kammer, Lisa Marie,Lipp, Benjamin,Opatz, Till
, p. 2379 - 2392 (2019)
The synthesis of vinyl sulfones and (α,β-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777.
Asymmetric Synthesis of γ-Amino-Functionalised Vinyl Sulfones: De Novo Preparation of Cysteine Protease Inhibitors
Cunningham, Laura,Evans, Paul,Shen, Wen
, (2022/02/10)
The enantioselective azo-based -amination of an aldehyde followed by a Horner Wadsworth Emmons-based vinyl sulfone formation is reported. The thus obtained optically active N,N'-diprotected trans-(phenylsulfonyl)vinyl hydrazine products were then converted into the corresponding N-functionalised trans-(phenylsulfonyl)vinyl amines. Specifically, reaction of 4-phenylbutanal with di-tert-butyl azodicarboxylate (DBAD) in the presence of L- or D-proline, followed by addition of diethyl [(phenylsulfonyl)methyl]phosphonate, gave either enantiomer of di-tert-butyl trans-1-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]hydrazine-1,2-dicarboxylate. The enantiomeric excesses of the (+)- and (-)-enantiomers prepared in this manner were in the range 86 89%. The conversion of these -hydrazino vinyl sulfones into the corresponding -amino-substituted compounds was achieved following a Boc deprotection, Zn reduction, N-functionalisation sequence. This three-step sequence was reasonably efficient (approx. 50%) and no erosion of enantiopurity was found to have taken place. The compounds accessed via this process include both enantiomers of tert-butyl trans-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]carbamate and epimeric dipeptide mimetics including 4-methyl-N-{(S)-1-oxo-3-phenyl-1-[((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino]propan-2-yl}piperazine-1-carboxamide (also known as K777).
Total Synthesis of K777: Successful Application of Transition-Metal-Catalyzed Alkyne Hydrothiolation toward the Modular Synthesis of a Potent Cysteine Protease Inhibitor
Kiemele, Erica R.,Wathier, Matthew,Bichler, Paul,Love, Jennifer A.
, p. 492 - 495 (2016/02/18)
We report the total synthesis of K777 and a series of analogues via alkyne hydrothiolation catalyzed by Wilkinson's complex (ClRh(PPh3)3). The alkyne hydrothiolation reactions proceeded with excellent regio- and diastereoselectivity