138775-03-8Relevant articles and documents
ISOBARIC MASS LABELS
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Paragraph 0023; 0024; 0174; 0175, (2019/01/04)
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: [in-line-formulae]X-L-M-Re[/in-line-formulae] wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a ma
Synthesis of Enantiopure Piperazines via Asymmetric Lithiation-Trapping of N-Boc Piperazines: Unexpected Role of the Electrophile and Distal N-Substituent
Firth, James D.,O'Brien, Peter,Ferris, Leigh
, p. 651 - 659 (2016/01/29)
A new method for the synthesis of enantiopure α-substituted piperazines via direct functionalization of the intact piperazine ring is described. The approach utilizes the asymmetric lithiation-substitution of an α-methylbenzyl-functionalized N-Boc piperaz
Asymmetric synthesis of chiral organofluorine compounds: Use of nonracemic fluoroiodoacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors
Myers,Barbay,Zhong
, p. 7207 - 7219 (2007/10/03)
Two stereoselective routes to a series of diastereomeric inhibitors of HIV protease, monofluorinated analogues of the Merck HIV protease inhibitor indinavir, are described. The two routes feature stereoselective construction of the fluorinated core subunits by asymmetric alkylation reactions. The first-generation syntheses were based on the conjugate addition of the lithium enolate derived-from pseudoephedrine α-fluoroacetamide to nitroalkene 12, a modestly diastereoselective transformation. A more practical second-generation synthetic route was developed that is based on a novel method for the asymmetric synthesis of organofluorine compounds, by enolate alkylation using optically active fluoroiodoacetic acid as the electrophile in combination with a chiral amide enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either enantiomeric form of the electrophile in ≥96% ee. Alkylation reactions with this stable and storable chiral fluorinated precursor are shown to proceed in a highly stereospecific manner. With the development of substrate-controlled syn- or anti-selective reductions of α-fluoro ketones 44 and 45 (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, Ki = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated in vitro, and the variation of potency as a function of inhibitor stereochemistry is discussed.