Mohamed F. El-Mansy and colleagues from Oregon State University developed a proline sulfonamide-catalyzed tandem reaction for the asymmetric synthesis of amine- and alcohol-containing bicyclo[2.2.2]octanes. They optimized reaction conditions and substrate scope for the reaction, and discovered a novel series of bicyclo[2.2.2]octanols. The reaction proceeds through an initial Michael addition followed by an intramolecular Mannich reaction to form the bicyclic products in good yields and stereoselectivities.
QSAR STUDY ON READY BIODEGRADABILITY OF CHEMICALS. Presented at the 3rd Chemo...Kamel Mansouri
The goal of this study was to predict ready biodegradation of
chemicals by QSAR modeling. The dataset used for this purpose was
produced by the Japanese Ministry of International Trade and Industry
(MITI) with experimental results according to the OECD test guideline
301C. Molecular descriptors from Dragon 6 were calculated. Variable
selection coupled with classification methods were applied to find the
most predictive models with low cross-validation error rate. The best
models were after that validated using the preselected test set to check
its prediction reliability and for further analysis.
QSAR STUDY ON READY BIODEGRADABILITY OF CHEMICALS. Presented at the 3rd Chemo...Kamel Mansouri
The goal of this study was to predict ready biodegradation of
chemicals by QSAR modeling. The dataset used for this purpose was
produced by the Japanese Ministry of International Trade and Industry
(MITI) with experimental results according to the OECD test guideline
301C. Molecular descriptors from Dragon 6 were calculated. Variable
selection coupled with classification methods were applied to find the
most predictive models with low cross-validation error rate. The best
models were after that validated using the preselected test set to check
its prediction reliability and for further analysis.
The presentation describes the prevalence of diabetes, secondary complications in diabetes, novel strategy promising to become treatment option, error by scientist leading to toxic compounds, efforts taken to circumvent the toxicity using drug design approach.
Synthesis, Characterization, Spectral (FT-IR, 1H, 13C NMR, Mass and UV) and B...Dr. Pradeep mitharwal
Bio-potent ligands, 2-hydroxy-N-phenylbenzamide hydrazinecarbothioamide(HPHTSCZH2) and 2-hydroxy-N-phenylbenzamide hydrazine carbodithioic benzyl ester (HPHCBESH2) have been synthesized by the condensation of 2-hydroxy-N-phenylbenzamide with hydrazinecarbothioamide and hydrazine carbodithioic benzyl ester, respectively and reacted with hydrated lanthanide chlorides. The coordination moieties of the ligands have been confirmed by various spectral studies. - See more at: http://www.sciencedomain.org/abstract.php?iid=271&id=16&aid=2488#sthash.6v3aFQIi.dpuf
Speciation And Physicochemical Studies of Some Biospecific CompoundsIOSR Journals
Abstract: A green, safer , efficient , eco-friendly approach for the synthesis of novel compounds which reveal biological and spermicidal activity. The nature of the pharmacophore decides the physiological reactivity of the compound.
In recent years, there is increased number of active pharmaceutical ingredients with high therapeutic activity, but very low water solubility. Thus, a great challenge for pharmaceutical technology is to manufacture successful formulations and efficient drug delivery systems to overcome these dissolution problems. In case of poorly water soluble drugs, dissolution is the rate limiting step in the process of drug absorption. So, bioavailability problems are associated with extremely hydrophobic drugs (aqueous solubility < 0.1 mg / ml at 370C)
The presentation describes the prevalence of diabetes, secondary complications in diabetes, novel strategy promising to become treatment option, error by scientist leading to toxic compounds, efforts taken to circumvent the toxicity using drug design approach.
Synthesis, Characterization, Spectral (FT-IR, 1H, 13C NMR, Mass and UV) and B...Dr. Pradeep mitharwal
Bio-potent ligands, 2-hydroxy-N-phenylbenzamide hydrazinecarbothioamide(HPHTSCZH2) and 2-hydroxy-N-phenylbenzamide hydrazine carbodithioic benzyl ester (HPHCBESH2) have been synthesized by the condensation of 2-hydroxy-N-phenylbenzamide with hydrazinecarbothioamide and hydrazine carbodithioic benzyl ester, respectively and reacted with hydrated lanthanide chlorides. The coordination moieties of the ligands have been confirmed by various spectral studies. - See more at: http://www.sciencedomain.org/abstract.php?iid=271&id=16&aid=2488#sthash.6v3aFQIi.dpuf
Speciation And Physicochemical Studies of Some Biospecific CompoundsIOSR Journals
Abstract: A green, safer , efficient , eco-friendly approach for the synthesis of novel compounds which reveal biological and spermicidal activity. The nature of the pharmacophore decides the physiological reactivity of the compound.
In recent years, there is increased number of active pharmaceutical ingredients with high therapeutic activity, but very low water solubility. Thus, a great challenge for pharmaceutical technology is to manufacture successful formulations and efficient drug delivery systems to overcome these dissolution problems. In case of poorly water soluble drugs, dissolution is the rate limiting step in the process of drug absorption. So, bioavailability problems are associated with extremely hydrophobic drugs (aqueous solubility < 0.1 mg / ml at 370C)
1. Mohamed F. El-Mansy, Jun Yong Kang,
Rajinikanth Lingampally and Rich G. Carter*
Department of Chemistry
Oregon State University
ACS meeting, San Diego
March14th, 2016
Paper number: ORGN 326
Proline sulfonamide-catalyzed, tandem process
for asymmetric synthesis of amine- and alcohol-
containing bicyclo[2.2.2]octanes
1
2. 2
• Background on proline sullfonamide catalysis.
• Optimizing the reaction conditions & reaction scope.
• Mechanism.
• Discovery of [2.2.2] bicyclic alcohols.
• Conclusion.
Outline
3. 3
Proline Sulfonamide Organocatalysis
Publications toward Proline Sulfonamides: (a) Yang, H.; Carter, R. G. Org. Lett. 2008, 10, 4649-4652. (b) Yang, H.; Carter, R. G.
J. Org. Chem. 2009, 74, 2246-2249. (c) Yang, H.; Carter, R. G. J. Org. Chem. 2009, 74, 5151-5156. (d) Yang, H.; Carter, R. G.
Tetrahedron 2010, 66, 4854-4859. (e) Yang, H.; Carter, R. G. Org. Lett. 2010, 12, 3108-3111. (f) Yang, H.; Carter, R. G. J. Org.
Chem. 2010, 76, 4929-4938. (g) Yang, H.; Mahapatra, S.; Cheong, P. H.-Y.; Carter, R. G. J. Org. Chem. 2010, 75, 7279-7290. (h)
Yang, H.; Carter, R. G. Synlett 2010, 2827-2838 (Review). (i) Pierce, M.; Johnston, R. C.; Mahapatra, S.; Yang, H.; Carter, R. G.;
Cheong, P. H.-Y. J. Am. Chem. Soc. 2012, 134, 13624–13631. (j) Yang, H., Banerjee, S.; Carter, R. G. Org. Biomol.
Chem. 2012, 10, 4851-4863. (k) Xiao, J.-A.; Liu, Q.; Ren, J.-W.; Liu, J.; Carter, R. G.; Chen, X.-Q.; Yang, H. Eur. J. Org. Chem. 2014,
2014, 5700-5704. (l) El Mansy, M. F.; Kang, J. Y.; Lingampally, R. Eur. J. Org. Chem. 2016, 150-157.
• Novel organocatalyst for facilitating asymmetric catalysis.
• Able to catalyze a range of reactions (e.g. aldol, Mannich, aza-Diels-Alder, Michael
addition, Yamada-Otani reaction).
• Nickname “Hua Cat” comes from postdoc Hua Yang who first prepared it.
• (R)- and (S)-Hua Cat have been commercialized with Sigma-Aldrich.
Cover Article -
Issue 25 (2012)
Catalog # (R) 733016
Catalog # (S) 733008
4. lycopodine Hua Cat
Evolution of Proline Sulfonamide Organocatalysis
Review: Yang, H.; Carter, R. G. Synlett 2010, 2827-2838
(Issue 19 Invited Account).
4
5. Yang, H.; Carter, R. G. Tetrahedron 2010, 66,4854-4859.
Yang, H., Banerjee, S.; Carter, R. G. Org. Biomol. Chem. 2012, 10, 4851-4863.5
Michael / Mannich Reaction Background
6. Optimization conditions
Entry Solvent dr er Yield %
a Neat 11:1 75.5:24.5 71
b Dioxane 8:1 81.0:19.0 53
c DCE 6:1 71.0:29.0 82
d Toluene 10:1 86.5:13.5 72
e PhCF3 9:1 86.7:13.3 80
f PhCF3(4 Å MS) 6:1 82.8:17.2 67
6
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
8. Systematic Approach for Synthesis of Aldehydes
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
8
9. Impact of Varying Electron Withdrawing Group
Entry EWG dr er Yield %
a CO2t-Bu 9:1 86.7:13.3 80
b CO2Et 9:1 nd* 79
c CO2Bn 6:1 83.1:16.9 53
d COSEt 20:1 71.6:28.4 64
e CN 3:1 88.9:11.1 87
9
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
* Compound proved unstable to HPLC analysis.
10. Role of Primary Amine on the [2.2.2] Bicycle Formation
Entry R dr er Yield %
a Bn- 9:1 nd* 79
b Ph- 20:1 73.9:26.1 32
c p-MeOC6H4- 20:1 94.3:5.7 50
d (3,5-CF3)C6H3CH2- 11:1 88.2:12.8 53
e CH2=CHCH2- 6:1 nd* 81
10
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
* Compound proved unstable to HPLC analysis.
11. 11
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
Further Exploration of Reaction Scope
12. 12
Mechanism of The Reaction
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
14. 14 El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
15. Discovery of [2.2.2] Bicyclic Alcohols
14
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
16. 16
Entry EWG dr er Yield %
a CO2Et 12:1 60.3:39.7 84
b CO2t-Bu - - 0
c CO2Bn 3:1 65.8:34.2 88
d C(O)SEt 3:1 nd 79
e CN >20:1 78.1:21.9 62
Effect of Electron Withdrawing Group
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
17. Conclusions
• A novel series bicyclo[2.2.2]octanols was discovered with good
yield and moderate stereoselctivity.
• A systematic way of making the aldehydes was developed.
• Generation of bicyclo[2.2.2]octanes containing amine derivatives in
good yield and excellent stereoselectivity.
17
18. 18
• Supervisor Rich G. Carter
• Carter Research Group Members
• Department of Chemistry
• Oregon State University
• National Science Foundation (CHE-1363105)
Acknowledgments
20. Poor selectivity in the cyano series
• Lack of interamolecular hydrogen bonding with enamine N-H
bond due to sp-hybridized nature of the nitrile.
El-Mansy, M. F.; Kang, J. Y.; Lingampally, R.; Carter, R. G. Eur. J. Org. Chem. 2016, 150-157.
Editor's Notes
EWG on quaternary stereocenter can be a universal building block.
No systematic way was known.
Unified method was developed using methylformate as electrophile.
Comment on the minor enamine at the end of the slide