Asymmetric Syntheses and Absolute Stereochemistry of 5,6-Dihydro-α-pyrones, A New Class of Potent HIV Protease Inhibitors

Judge, Thomas M.; Phillips, Gillian; Morris, Joel; Lovasz, K. D.; Romines, Karen R.; Luke, George P.; Tulinsky, John; Tustin, J. M.; Chrusciel, R. A.; Dolak, Lester A.; Mizsak, S. A.; Watt, W.; Velde, S. L. Vander; Strohbach, and J. W.; Gammill, Ronald B.

doi:10.1021/ja963434w

Cited by 45 publications

(22 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of the acidity of the solution and the catalyst was probed, and showed that Ir catalysts are significantly more acidic than their Rh counterparts. It transpired from the study that as the electron 45 density at the iridium increased, the hydride became less acidic, and conversely electron withdrawing groups on the iridium increase their acidity.…”

Section: Heterocycle Tuningmentioning

confidence: 99%

“…40 Following the reasoning outlined in 40 the ligand design section, the tuning of the ligand was pivotal to obtaining good results, hence the use of highly similar catalysts. The choice of the N linker atom to the phosphine group combined with the choice of a thiazole heterocycle lead to a highly enantioselective iridium catalyst, which was able to hydrogenate 45 with the electron poor alkenes efficiently. This demonstrates the importance of harnessing and matching the electronics of the olefin substrate.…”

Section: Trifluoromethylated Olefinsmentioning

confidence: 99%

“…45 The importance of the reaction can be derived from the number of attempts and competing methods devised to carry it out. Both copper and ruthenium have been employed in asymmetric reductions of α,β-unsaturated carbonyls, 46 however they are difficult reactions to 45 carry out due to the water sensitivity of the hydride donors. 47 This reaction was also conducted using enzyme catalysis, however the reaction was both slow and poor in yield.…”

Section: Estersmentioning

confidence: 99%

“…Kagan's DIOP ligand 8 and the aforementioned DIPAMP, developed by Knowles for the L-DOPA process (based on Wilkinson's catalyst) are amongst the most famous examples of this. Similarly, the optimisation of N,P- 45 ligated iridium complexes lead Pfaltz to publish in 1998 a new catalyst, a chiral analogue to Crabtree's, using a PHOX type ligand to bind to the metal. This discovery birthed the field of iridium catalysed asymmetric hydrogenation, and his group has since remained at the forefront of the field.…”

Section: Introductionmentioning

confidence: 99%

“…A similar DFT study was conducted by Burgess for an N,C-ligated complex and also points toward an Ir (III/V) process. 17 Due to the similarity of the two proposed cycles and the difficulty to detect the intermediates in situ, neither has been 45 disproved yet, as they provide hints but no definite evidence. Ligand design and optimisation Figure 2.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Iridium catalysis: application of asymmetric reductive hydrogenation

Cadu

Andersson

2013

Dalton Trans.

View full text Add to dashboard Cite

PostprintThis is the accepted version of a paper published in Dalton Transactions. This paper has been peerreviewed but does not include the final publisher proof-corrections or journal pagination. Iridium, despite being one of the least abundant transition metals, has known several uses. N,P-ligated 5 iridium catalysts are used to perform many highly selective reactions. These methodologies have been developed extensively over the past 15 years. More recently, the application of iridium N,P catalysts in asymmetric hydrogenation has been a focus, to find novel applications and to expand on their current synthetic utility. The aim of this perspective is to highlight the advances made by the Andersson group.

show abstract

Section: Heterocycle Tuningmentioning

confidence: 99%

Section: Trifluoromethylated Olefinsmentioning

confidence: 99%

Section: Estersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Iridium catalysis: application of asymmetric reductive hydrogenation

Cadu

Andersson

2013

Dalton Trans.

View full text Add to dashboard Cite

show abstract

Structure-based discovery of tipranavir disodium (PNU-140690E): A potent, orally bioavailable, nonpeptidic HIV protease inhibitor

Thaisrivongs

Strohbach

1999

Biopolymers

View full text Add to dashboard Cite

Peptidomimetics for Drug Design

Estiarte

Rich

2003

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The past and present role of peptidomimetics to drug discovery and protein design is summarized. The historical evolution of this area of research and the current state‐of‐the‐art research strategies are described. A detailed description of each of the peptidomimetics types that have appeared in the literature so far is discussed. Some examples are used to illustrate the drug design process that proceeds from the native peptide to a completely non‐peptide peptidomimetic structure. Special attention is given to important pharmaceutical targets such as the cysteine, metallo, serineor aspartic proteases, integrins, G‐protein–coupled receptors, etc. The principles currently used are highlighted in the discussions of some of the most successful examples. It is obvious that major progress in this area is primarily derived of recent advances in all aspects of science. Molecular modeling, X‐ray crystallography, and high field NMR have greatly contributed to this endeavor. Peptidomimetic inhibitors were traditionally developed by modifying peptide bonds, by mimicking the transition states for enzyme‐catalyzed reactions, or by constraining the conformational mobility of a peptide‐derived chain; the latter was used to overcome some of the pharmacokinetic barriers encountered in using peptides as drugs. Lately, these difficulties have been partially solved with rational drug design of de novo compounds. Several methods have been successfully applied, with noteworthy examples currently in clinical trials, and many others are expected in the near future. It would be wrong, however, to imply that this process is a universal panacea. New ideas are urgently needed to produce clinical candidates faster and to solve some of the undesired pharmacokinetic issues.

show abstract

Asymmetric Syntheses and Absolute Stereochemistry of 5,6-Dihydro-α-pyrones, A New Class of Potent HIV Protease Inhibitors

Cited by 45 publications

References 9 publications

Iridium catalysis: application of asymmetric reductive hydrogenation

Iridium catalysis: application of asymmetric reductive hydrogenation

Structure-based discovery of tipranavir disodium (PNU-140690E): A potent, orally bioavailable, nonpeptidic HIV protease inhibitor

Peptidomimetics for Drug Design

Contact Info

Product

Resources

About