ACD/Labs NMR Software Symposium

Transcription

1 ACD/Labs NMR Software Symposium Seven Novel Structures Generated with Computer- Assisted Structure Elucidation Arvin Moser SMASH September 11, 2016

2 Galileo Galilei Relevant Quote " All truths are easy to understand once they are discovered; the point is to discover them ".* *Angels in the workplace : stories and inspirations for creating a new world of work (1999) by Melissa Giovagnoli 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 2

3 MF, 1 H, 13 C, HSQC, HMBC, CSY in solvent CD 3 D, molecule(s) have been generated by Correlation Spectroscopy Based Generator and 42 molecule(s) have been stored. Generation time: 23 seconds TP Structure Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. rganic Letters, 2015, 17, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 3

4 Additional correlations from DMS-d 6 data and analogue Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. rganic Letters, 2015, 17, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 4

5 Hydrogen deficient C 30 H in MeH-d 4 (400 MHz) 1 in DMS-d 6 (400 MHz) Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. rganic Letters, 2015, 17, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 5

6 Synthetic Product H 3 C H H 1 isomerization 2 dimerization H 3 C Product 4 [] ring-opening 3 reduction Expected 6? mcpba 5 H 2. Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside ut: A Rearrangement Triggered by an Enol Ether Epoxidation. Chemistrypen, June 2015, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 6

7 Red arrow = 1,1-HD-ADEQUATE With 1,1-ADEQUATE (40 Hz) & LR-HSQMBC (2 Hz & 4 Hz)* Without 1,1- ADEQUATE &HSQMBC* Isomers Generated Time (seconds) Top Candidate 1 1 *Data also includes: MF+NMR ( 1 H, 13 C, HSQC, CSY, 1 H- 13 C HMBC (opt. 10 Hz)) Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside ut: A Rearrangement Triggered by an Enol Ether Epoxidation. Chemistrypen, June 2015, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 7

8 TP Structure With 1,1-ADEQUATE data 1 J CC Volume = J CC Volume = F2 Chemical Shift (ppm) The Fuzzy generator was invoked due to a 2 J CC correlation in the 1,1-ADEQUATE M. Elyashberg, K.A. Blinov, A.J. Williams, S.G. Molodtsov, G.E. Martin Fuzzy Structure Generation: A New Efficient Tool For Computer- Aided Structure Elucidation (CASE) J. Chem. Inform. Model., 47: , Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside ut: A Rearrangement Triggered by an Enol Ether Epoxidation. Chemistrypen, June 2015, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 8

9 Natural Product - See Clark s Presentation TP Structure 3. Xing-Nuo Li, Clark D. Ridge, Eugene P. Mazzola, Jianghao Sun, svaldo Gutierrez, Arvin Moser, Joseph C. DiMartino, Scott A. MacDonald and Pei Chen. Application of a Computer-Assisted Structure Elucidation Program for the Structural Determination of a New Terpenoid Aldehyde with an Unusual Skeleton. Magnetic Resonance in Chemistry, 2016, accepted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 9

10 Marine Natural Product Color in situ photograph of Eudistoma sp. (underwater) 4. Susanna T. S. Chan, Roger R. Nani, Evan A. Schauer, Gary E. Martin, Robert T. Williamson, Josep Saurí, Alexei V. Buevich, Wes A. Schafer, Andrew K. L. Goey, William D. Figg, Tanya R. Ransom, Curtis J. Henrich, Tawnya C. McKee, Arvin Moser, Scott A. McDonald, Shabana Khan, James B. McMahon, Martin J. Schnermann, Kirk R. Gustafson. Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold, JACS, 2016, submitted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 10

11 Blue=CSY, Black=HMBC, Red=1H-15N HMBC TP Structure Susanna T. S. Chan, Roger R. Nani, Evan A. Schauer, Gary E. Martin, Robert T. Williamson, Josep Saurí, Alexei V. Buevich, Wes A. Schafer, Andrew K. L. Goey, William D. Figg, Tanya R. Ransom, Curtis J. Henrich, Tawnya C. McKee, Arvin Moser, Scott A. McDonald, Shabana Khan, James B. McMahon, Martin J. Schnermann, Kirk R. Gustafson Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold, JACS, submitted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 11

12 Synthetic Products 5. David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EURMAR, 2016 Denmark. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 12

13 Expansion of HMBC data: normal 1 H-{ 13 C} HMBC (left) and band-selective 1 H-{ 13 C} HMBC (right) spectra of the first isomer. David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EURMAR, 2016 Denmark. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 13

14 NESY_01.fid.esp Expansion of the NESY spectrum of the second isomer around the region of the acetyl methyl signal at 3.70 ppm. The correlations to both the aromatic rings are visible. C H H 3 C ppm H 3 C H 3 C H 3 C H 3 C First Second ppm David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EURMAR, 2016 Denmark. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 15

15 6. Elyashberg, M. E. Moldtsov, S., Blinov K., Williams, A.J. J.Nat. Prod. 2013, 76, Liao, W.-Y.; Shen, C.-N.; Lin, L.-H.; Yang, Y.-L.; Han, H.-Y.; Chen, J.-W.; Kuo, S.-C.; Wu, S.-H.; Liaw, C.-C. J. Nat. Prod. 2012, 75, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 16

16 7. M. E. Elyashberg, K. A. Blinov, S.G. Molodtsov, T.S. Churanova, A.J. Williams. ChemSpider Journal of Chemistry. 2009, 889. N H N H H H 3 C J. Nat. Prod. 2004, 67, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 17 H H 3 C H C

17 7. M. E. Elyashberg, K. A. Blinov, S.G. Molodtsov, T.S. Churanova, A.J. Williams. ChemSpider Journal of Chemistry. 2009, 889. H N J. Nat. Prod. 2004, 67, H H 3 C H C 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 18

18 Molecular Weight MS, IR, known fragments Bad list Recap: ACD/Structure Elucidator

19 Case 1: Fragment Generation H H A A H H Case#1: The 2-hydroxy-3-methylbut-2-enedial fragment was seen during the generation by ACD/Structure Elucidator. *Data also includes: MF & 5 mm cryoprobe NMR [ 1 H (600 MHz), 13 C (125 MHz), HSQC-DEPT (600 MHz), CSY (500 MHz), TCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)] Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 20

20 Case 2: User Fragments?? *Data also includes: MF & 5 mm cryoprobe NMR [ 1 H (600 MHz), 13 C (125 MHz), HSQC-DEPT (600 MHz), CSY (500 MHz), TCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)] Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 21

21 Case 5: ADEQUATE Generation Structure Known 1 H 2 H 3 C H H 3 C H H 3 C H H H d N ( 13 C): Formula: C 28 H 26 8 FW: d N ( 1 H): d N ( 13 C+ 1 H): d N ( 13 C): Formula: C 28 H 26 8 FW: d N ( 1 H): d N ( 13 C+ 1 H): Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 22

22 Case 2: Re-evaluated in 2016 *Data also includes: MF & 5 mm cryoprobe NMR [ 1 H (600 MHz), 13 C (125 MHz), HSQC-DEPT (600 MHz), CSY (500 MHz), TCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)] Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted. 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 23

23 Solution: Introduce Free Structure Elucidation Tutorial Software 9/28/

24 Enhance your Elucidation Skills: Structure Elucidator Tutorials Arvin Moser and Brent G. Pautler. The fundamentals behind solving for unknown molecular structures using computer-assisted structure elucidation: a free software package at the undergraduate and graduate levels. Magnetic Resonance in Chemistry, 2016, 54, /28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 25

25 Some Humor I make bad chemistry jokes because all the good ones Argon Q: Why do chemists enjoy working with ammonia? A: Because it's pretty basic stuff. Q: What did one ion say to the other? A: I've got my ion you. Q: What did the chemist say when he found 2 isotopes of helium? A: HeHe 9/28/2016 Advanced Chemistry Development, Inc. (ACD/Labs) 26

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