A new route to hydrophobic amino acids using copper-promoted reactions of serine-derived organozinc reagents

Deboves, Hervé J. C.; Grabowska, Urszula; Rizzo, Adriana; Jackson, Richard F. W.

doi:10.1039/b007032g

Cited by 21 publications

(13 citation statements)

References 11 publications

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“…Copper(I)-promoted S N 2’ reaction of a serine-derived organozinc reagent with allylic electrophiles has been previously used to synthesize amino acids that contain a γ-stereogenic center. 17,18 This method was appealing because it would provide dhML (as the Boc methyl ester) in only two steps from the inexpensive chiral building block, Boc-( S )-serine-OMe. 17 After extensive optimization aimed at improving S N 2’ vs. S N 2 selectivity and conversion (Supplementary Figure 1), we obtained Boc-dhML-OMe 3 in 43% isolated yield (1.6 g) through the use of 50 mol% CuBrDMS and 2 equivalents of crotyl chloride (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

“…17,18 This method was appealing because it would provide dhML (as the Boc methyl ester) in only two steps from the inexpensive chiral building block, Boc-( S )-serine-OMe. 17 After extensive optimization aimed at improving S N 2’ vs. S N 2 selectivity and conversion (Supplementary Figure 1), we obtained Boc-dhML-OMe 3 in 43% isolated yield (1.6 g) through the use of 50 mol% CuBrDMS and 2 equivalents of crotyl chloride (Figure 2a). Boc to Fmoc exchange, followed by ester hydrolysis, provided Fmoc-dhML 5 , which was incorporated into the linear heptapeptide as described below.…”

Section: Resultsmentioning

confidence: 99%

“…The copper(I)-promoted SN2' reaction between a serine-derived organozinc reagent and allylic electrophiles has been previously exploited to synthesize amino acids that contain a gstereogenic center. [12][13] This method was appealing because it would provide dhML (as the Boc methyl ester) in only two steps from the inexpensive chiral building block, Boc-(S)-serine-OMe.…”

Section: Efficient Synthesis Of Dehydromethyl Leucine (Dhml)mentioning

confidence: 99%

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Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3

Wang¹,

Oltion²,

Al-Khdhairawi

et al. 2020

Preprint

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Ternatin and related cyclic peptides inhibit the elongation phase of protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A), a potential therapeutic vulnerability in cancer and viral infections. The cyclic peptide natural product “A3” appears to be related to ternatin, but its complete structure is unknown and only 4 of its 11 stereocenters have been assigned. Hence, A3 could be any one of 128 possible stereoisomers. Guided by the stereochemistry of ternatin and more potent structural variants, we synthesized two A3 epimers, “SR-A3” and “SS-A3”. We found that synthetic SR-A3 is indistinguishable from naturally derived A3 and potently inhibits cancer cell proliferation. Relative to SS-A3 and previously characterized ternatin variants, SR-A3 exhibits a dramatically enhanced duration of action. This increase in cellular residence time is conferred, stereospecifically, by a single β-hydroxy group attached to N-methyl leucine. SR-A3 thus exemplifies a mechanism for enhancing the pharmacological potency of cyclic peptide natural products via side-chain hydroxylation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Efficient Synthesis Of Dehydromethyl Leucine (Dhml)mentioning

confidence: 99%

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Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3

Wang¹,

Oltion²,

Al-Khdhairawi

et al. 2020

Preprint

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“…SCHEME 1 species 16 and used it in the synthesis of unnatural amino acids. 22 Additionally Knochel and coworkers have reacted various zinc iodides with chlorodiphenylphosphine to obtain phosphines in high yields. 23 A combination of these precedents provides a facile route to a number of phosphine amino acids.…”

Section: Synthesis Of Phosphine-containing Alanine Derivativesmentioning

confidence: 99%

Synthesis of phosphine containing amino acids: Utilization of peptide synthesis in ligand design

et al. 2005

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Combinatorial chemistry has recently burst on the scene as a valuable tool for the discovery of new drug candidates. The ability to synthesize hundreds of compounds for screening is a useful complement to rational drug design. There are many similarities between the design of new therapeutic agents and the development of new asymmetric ligands, the most important of which is the limitation of a rational design strategy. For this reason a program was begun that would allow the use of combinatorial technology in the development of new ligands for transition metal catalyzed asymmetric reactions. Because of the large number of catalytic reactions they are involved in the system was based around phosphine ligands. This paper reports the synthesis of phosphine derivatives of alanine, proline, and the aromatic amino acids tyrosine and hydroxyphenylglycine. Examples of the use of these amino acids in the synthesis of peptides possessing helical and beta-turn secondary structures are presented. Metal complexes of these peptide-based ligands are used in hydrogenation and alkylation reactions.

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“…13,14 Jackson has converted this functionalized amino acid to zinc copper species 2 and used it in the synthesis of unnatural amino acids. 15 Additionally Knochel has reacted various zinc iodides with chlorodiphenylphosphine to obtain phosphines in high yields. 16 A combination of these precedents provides a facile route to a number of phosphine amino acids (Scheme 2).…”

mentioning

confidence: 99%

Preparation of Diphenylphosphinoserine and Synthesis of Other Phosphine Containing Amino Acids Using Zinc/Copper Reagents

Greenfield¹,

Gilbertson²

2001

Synthesis

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A new route to hydrophobic amino acids using copper-promoted reactions of serine-derived organozinc reagents

Cited by 21 publications

References 11 publications

Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3

Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3

Synthesis of phosphine containing amino acids: Utilization of peptide synthesis in ligand design

Preparation of Diphenylphosphinoserine and Synthesis of Other Phosphine Containing Amino Acids Using Zinc/Copper Reagents

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