Synthesis and LC-MS/MS analysis of desmosine-CH<sub>2</sub>, a potential internal standard for the degraded elastin biomarker desmosine

Murakami, Yuko; Suzuki, Rina; Yanuma, Hiroto; He, Jiangtao; Ma, Shuren; Turino, Gerard M.; Lin, Yong Y.; Usuki, Toyonobu

doi:10.1039/c4ob01438c

Cited by 18 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, this two-electron sequence can be traced back to the coupling of alkynyl unit 62 and its requisite amino acid partner 61 , but nonstrategic manipulations detract from its conciseness and scalability. 27 By exploiting the radical synthon 63 , accessed from glutamic acid derivative 64 , 60 was synthesized in one step following its direct coupling to the alkynyl zinc 65 . This alkynylation reaction also proceeds on one-mole scale with little change in yield.…”

Section: Tactical Applications Of Radical Cross-couplingmentioning

confidence: 99%

See 1 more Smart Citation

Radical Retrosynthesis

2018

View full text Add to dashboard Cite

In The Logic of Chemical Synthesis, E. J. Corey stated that the key to retrosynthetic analysis was a "wise choice of appropriate simplifying transforms" ( Corey , E. J. ; Cheng , X.-M. The Logic of Chemical Synthesis ; John Wiley : New York , 1989 ). Through the lens of "ideality", chemists can identify opportunities that can lead to more practical, scalable, and sustainable synthesis. The percent ideality of a synthesis is defined as [(no. of construction rxns) + (no. of strategic redox rxns)]/(total no. of steps) × 100. A direct consequence of designing "wise" or "ideal" plans is that new transformations often need invention. For example, if functional group interconversions are to be avoided, one is faced with the prospect of directly functionalizing C-H bonds ( Gutekunst , W. R. ; Baran , P. S. Chem. Soc. Rev. 2011 , 40 , 1976 ; Brückl , T. ; et al. Acc. Chem. Res. 2012 , 45 , 826 ). If protecting groups are minimized, methods testing the limits of chemoselectivity require invention ( Baran , P. S. ; et al. Nature 2007 , 446 , 404 ; Young , I. S. ; Baran , P. S. Nat. Chem. 2009 , 1 , 193 ). Finally, if extraneous redox manipulations are to be eliminated, methods directly generating key skeletal bonds result ( Burns , N. Z. ; et al. Angew. Chem., Int. Ed. 2009 , 48 , 2854 ). Such analyses applied to total synthesis have seen an explosion of interest in recent years. Thus, it is the interplay of aspirational strategic demands with the limits of available methods that can influence and inspire ingenuity. E. J. Corey's sage advice holds true when endeavoring in complex molecule synthesis, but together with the tenets of the "ideal" synthesis, avoiding concession steps leads to the most strategically and tactically optimal route ( Hendrickson , J. B. J. Am. Chem. Soc. 1975 , 97 , 5784 ; Gaich , T. ; Baran , P. S. J. Org. Chem. 2010 , 75 , 4657 ). Polar disconnections are intuitive and underlie much of retrosynthetic logic. Undergraduates exposed to multistep synthesis are often taught to assemble organic molecules through the combination of positively and negatively charged synthons because, after all, opposites attract. Indeed, the most employed two-electron C-C bond forming reactions today are those based upon either classical cross-coupling reactions (e.g., Suzuki, Negishi, or Heck) or polar additions (aldol, Michael, or Grignard). These reactions are the mainstay of modern synthesis and have revolutionized the way molecules are constructed due to their robust and predictable nature. In contrast, radical chemistry is sparsely covered beyond the basic principles of radical chain processes (i.e., radical halogenation). The historical perception of radicals as somewhat uncontrollable species does not help the situation. As a result, synthetic chemists are not prone to make radical-based strategic bond disconnections during first-pass retrosynthetic analyses. Recent interest in the use of one-electron radical cross-coupling (RCC) methods has been fueled by the realization of their uniquely chemoselective profiles a...

show abstract

Section: Tactical Applications Of Radical Cross-couplingmentioning

confidence: 99%

“…This direct tactical approach obviates the necessity for toxic Sn reagents and prefunctionalization, providing a facile, programmable installation of the fluoromethyl moiety. 27…”

Section: Tactical Applications Of Radical Cross-couplingmentioning

confidence: 99%

Radical Retrosynthesis

2018

View full text Add to dashboard Cite

show abstract

“…The development of such a reaction was motivated by several useful alkynes that are extremely laborious to access. An illustrative example is depicted in Figure A, wherein an alkynyl amino acid derivative ( 3 ) was accessed from a parent amino acid ( 1 ) in four steps . This type of unnatural amino acid has proven to be of critical value to practitioners in chemical biology and drug discovery .…”

Section: Figurementioning

confidence: 99%

“…The reaction of protected glutamic acid 2 was successful via isolation of the RAE (72 % yield) and in situ activation (69 % yield). This simple method provides for a significant improvement to the state of the art in preparing this valuable intermediate . Furthermore, this reaction was conducted on 1 mol scale, and the product was isolated in 73 % yield with no erosion of enantiopurity.…”

Section: Figurementioning

confidence: 99%

Decarboxylative Alkynylation

et al. 2017

View full text Add to dashboard Cite

The development of a new decarboxylative cross‐coupling method that affords terminal and substituted alkynes from various carboxylic acids is described using both nickel‐ and iron‐based catalysts. The use of N‐hydroxytetrachlorophthalimide (TCNHPI) esters is crucial to the success of the transformation, and the reaction is amenable to in situ carboxylic acid activation. Additionally, an inexpensive, commercially available alkyne source is employed in this formal homologation process that serves as a surrogate for other well‐established alkyne syntheses. The reaction is operationally simple and broad in scope while providing succinct and scalable avenues to previously reported synthetic intermediates.

show abstract

“…An illustrative example is depicted in Figure 1A, wherein an alkynyl amino acid derivative ( 3 ) was accessed from a parent amino acid ( 1 ) in 4 steps. 8 This type of unnatural amino acid has proven to be of critical value to practitioners in chemical biology and drug discovery. 2d In contrast, a mild decarboxylative alkynylation strategy could dramatically simplify the pathway to 3 because the native carboxylate of a glutamic acid ( 2 ) could be viewed as a progenitor of the alkyne unit without redox-manipulations.…”

mentioning

confidence: 99%

Decarboxylative Alkynylation

et al. 2017

View full text Add to dashboard Cite

The development of a new decarboxylative cross-coupling protocol that affords terminal and substituted alkynes from various carboxylic acids is described using both nickel- and iron-based catalysts. The use of N-hydroxytetrachlorophthalimide (TCNHPI) esters is crucial to the success of the transformation, and the reaction is amenable to in situ carboxylic acid activation. Additionally, an inexpensive, commercially-available alkyne source is employed in this formal homologation process that serves as a surrogate for other well-established alkyne syntheses. The reaction can be conducted on a mole scale, and the conditions are mild, operationally simple, and broad in scope while providing succinct avenues to previously reported synthetic intermediates.

show abstract

Synthesis and LC-MS/MS analysis of desmosine-CH₂, a potential internal standard for the degraded elastin biomarker desmosine

Cited by 18 publications

References 35 publications

Radical Retrosynthesis

Radical Retrosynthesis

Decarboxylative Alkynylation

Decarboxylative Alkynylation

Contact Info

Product

Resources

About

Synthesis and LC-MS/MS analysis of desmosine-CH2, a potential internal standard for the degraded elastin biomarker desmosine

Cited by 18 publications

References 35 publications

Radical Retrosynthesis

Radical Retrosynthesis

Decarboxylative Alkynylation

Decarboxylative Alkynylation

Contact Info

Product

Resources

About

Synthesis and LC-MS/MS analysis of desmosine-CH₂, a potential internal standard for the degraded elastin biomarker desmosine