Synthesis of both D- and L-Fmoc-Abu[PO(OCH2CHCH2)2]-OH for solid phase phosphonopeptide synthesis

The Synthesis of Methylated, Phosphorylated, and Phosphonated 3′‐Aminoacyl‐tRNASec Mimics

“…The asymmetric synthesis of N ‐Fmoc‐ and O ‐allyl‐protected ( S )‐2‐amino‐4‐phosphonobutyric acid ( 9 ) that was required for the solid support 10 , was optimized from an early report in the literature22 and based on Schöllkopfs bislactim ether 6 and the bromoethylphosphonate ester 7 (Scheme ). Importantly, although the hydrolysis of the bislactim ether function of 8 to the corresponding amino acid ester can be performed under very mild acidic conditions, enzymatic hydrolysis of the ester by using chymotrypsin had to be used to generate the free carboxylic acid moiety (see the Supporting Information).…”

“…Consequently, the same approach could, in principle, be extended to methylated and/or phosphorylated peptidyl–tRNA conjugates. Also, the serine analogue Abu(p), introduced as a functional part of an adenosine‐modified solid support, could be used as an amino acid building block (Fmoc‐Abu(pAll 2 )) for incorporation at internal positions of the peptidyl moiety 22. Finally, our work included the development of an efficient one‐pot, three‐strand tRNA ligation protocol for tRNA Sec , which is generally applicable to other tRNA species containing a long variable loop.…”

“…Also, the serine analogue Abu(p), introduced as a functional part of an adenosine-modified solid support, could be used as an amino acid building block (Fmoc-Abu(pAll 2 )) for incorporation at internal positions of the peptidyl moiety. [22] Finally, our work included the development of an efficient one-pot, three-strand tRNA ligation protocol for tRNA Sec , which is generally applicable to other tRNA species containing a long variable loop. We have prepared structurally complex tRNA Sec mimics that carry modified amino acid moieties, which may, interfere with discrete steps in the biosynthetic cycle of selenocysteine.…”

ω -Phosphinyl-α -Amino Acids: Synthesis, and Development towards Use as Therapeutic Agents

“…Section 2.2.2) has also been generated using Schöllkopf's methodology [32]. In addition, high 2,5-trans-diastereoselectivity in the alkylation/addition of R-52 has been achieved to generate (2S,5R)-57 using an equimolar solution of O,O-diethyl bromoethylphosphonate (Component A, Scheme 8b) containing 5% of the vinylphosphonate (Component B) [34,40]. Diastereoselectivity in this case was rationalised as due to the faster rate of reaction with 'B' (>> 'A'), and continual replenishment of this component through trapping of the resulting phosphonate carbanion by 'A', leading to dehydrohalogenation.…”

Design and synthesis of a reagent for solid-phase incorporation of the phosphothreonine mimetic (2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) into peptides in a bio-reversible phosphonyl-bis-pivaloyloxymethyl (POM) prodrug form

“…However, in cellular systems the bioavailabilty of phosphopeptides may be limited by the enzymatic lability of the phosphoryl ester bond toward phosphatases and poor membrane transport of the phosphoryl di-anionic species. While replacement of the phosphoryl ester oxygen by methylene or fluoromethylenes has addressed issues related to phosphatase hydrolysis for pTyr (Burke and Lee 2003), pSer (Shapiro et al 1993; Perich 1994; Nair et al 1995; Panigrahi et al 2009) and pThr (Berkowitz et al 1966; Otaka et al 2000; Liu et al 2009), cell membrane transit can still be limited by the di-anionic charge of the resulting phosphonic acids.…”