1977-78 Annual Report RR-00612 Dr. H. J. Stoklosa Central Rsch & Development Dept E. I. du Pont de Nemours & Co. Wilmington, Delaware 19898 Dr. F. Street AEI Scientific Apparatus, Ltd. Barton Dock Road Urmston, Manchester M31 2LD England Dr. Robert M. Supnik Massachusetts Computer Assoc. 26 Princess Street Wakefield, Massachusetts 01880 Dr. H. G. J. Teisman Netherlands Institute for Dairy Research Post Office Box 20 EDE, NETHERLANDS Dr. Gareth Templeman Rsch and Development Lab. The Pillsbury Company 311 Second Street Southeast Minneapolis, Minnesota 55414 Dr. Ernst Weber Varian MAT P.O. Box 144062 Bremen, West Germany Dr. J. Wyatt Code 6110 Naval Research Laboratory Washington, D. C. 20375 101 Section 6.2 1977-78 Annual Report RR-00612 Section 6.2 7 APPENDICES 7.1 Appendix A The Structures of All 4—Dimethyl Marine Sterols Reported to the Beginning of 1977. Each sterol is given a unique number which is used in subsequent discussions in the text. The molecular weight (M* and common trivial name are given for each sterol. The nuclei all possess alternating trans-anti stereochemistry at the ring junctures, except the 5* stanols (farthest right hand column) which possess a cis-A,B ring fusion. The number of carbon atoms in the side chains is indicated along the left hand border. See p. 102a for Appendix |. 102 MARINE STEROL SIDE CHAINS $100 CHAINS sMoart no e a < 300 FUNGISTEROL (a)=SPtmasTEROLs az CMON TLLASTEROL saz a -FUCOsTERGL lz 2? Appendix A. MARINE STEROL NUCLEI 102a 1977-78 Annual Report RR-00612 Section 7.2 7.2 Appendix B Sources of Sterol Mass Spectra. Sterol: names listed on the following two pages indicate spectra that were obtained from the old mass spectral files of Prof. Carl Djerassi. The spectra are divided into two groups: (1) sterols that are known to occur in marine sources, i.e. "4-demethyl marine sterol mass spectra" and (2) all other sterol mass spectra from those files grouped under "4-demethyl synthetic sterol mass spectra". The original CD number is given. These spectra were incorporated in the National Institutes of Health MSSS mass spectral data bank, which is available internationlly to researchers employing mass spectral identifications systems. See: S. R. Heller, Biomed. Mass., 1, 207 (1974). All other mass spectra listed in Appendix 1 have been obtained by running mass spectra of authentic samples provided by researchers from around the world. The samples were either pure compound or mixtures requiring subsequent purifications here. I would,therefore, like to join Professor Djerassi in thanking these researchers. - Dr. Aringer Dr. J. Mathieu (Karolinska Siukhuset, Stockholm) (Roussel-UCLAF Research Laboratories) 'Dr. J. T. Baker and Dr. R. J. Wells (Roche Research Institute of Dr. P. J. Scheuer Pha rmacology, Australia) (University of Hawaii) Dr. M. Barbier Dr. F. J. Schmitz (Institut de Chimie des Substances (University of Oklahoma) Naturelles, France) Dr. R. H. Thomson Dr. L. J. Goad (University of Aberdeen) (University of Liverpool, England) Dr. A. J. Weinheimer Dr. A. Kanazawa (University of Oklahoma) (University of Kagoshima, Japan) Dr. B. A. Knights . (University of Glasgow, Scotland) Dr. M. Kobayashi (Hokkaido University, Japan) I would also like to thank Willian A. Dow, Stanford University, for samples of aplysterol 90 and didehydroaplysterol 77 which he isolated from Verongia fistularis. 103 U=DEMETHYL SYNTHETIC STEROL MASS SPECTRA FROM THE FILES OF CARL DJERASSI JAN, 7, 1976 we ee ee me ee eee ODN OUI EWN an rumnecwnye Oo fur rT TN eww Oo 02 SO# . CATA COR MW NS FORMULA STEROL Wot 05203 276 CEC~103 C19H320 SALPHA*ANDROSTAN@3BETA*OL >» 99 16309 300 AEI=MS9 C21H320 (17(20)Z)=PREGNA#5,17(20)=DIEN=3BETA#OL m221 99999 302 MATCH4 C2LH340 PREG=SwEN=3BETA=OL 219 Q9576 316 AET#MS9 C2ea2Hs4uo 23, 24~*DINOR=CHOL=20"EN=3BETA=OL, mmm Udit 328 U C23H340 2UeNORMCHOLA*5, 22°DIEN=SRETA*OL S673 20636 342 U C24H380 (C22E)-CHOLA#5,22=DIEN@=3BETA*OL 5672 20637 342 Uo=t«; C24H380 (22Z)=CHOLA=5,22e«DIEN=3BETA=0L 78 {8697 346 AEIT-MS9 C24Hu20 SBETA=CHOLAN=3BETA~Ol, 76 18743 346 U C24Ha2ed SBETA@CHOLAN@=3ALPHA#OL S671 ° 20644 356 U C25H400 (222) "26, 27*DINOR=CHOLESTA"5S, 22=DIEN@SRETAROL 5670 20639 356 V C25H400 (226) %26,27*DINOR=CHOLESTA#5, 22-01 EN@3BETAROL 5669 20659 370 U C26H420 (222) =2UeNOR@CHOLESTA=S,2e~DIEN=3BETAWOL 5345 99690 370 U C26H420 2U~NORACHOLESTA=S;,eS"°DIEN=3BETA*OL 53ugq 99691 370 VU C26H420 Z4UeNORWCHOLESTA=S,23=DIEN=3BETA=OL Y69{ 18661 382 MAT=CHA C2e7H420 CHOLESTA#5,20C21),24nTRIEN@SBETA@OL, 4692 {18659 382 MAT*CHU C27H420 (1 7C20)E)=CHOLESTA=5,17(20), 2UnTRIEN@3BETA=OL - §667 20525 384 U C27H440 (22Z) 27H NOR=24@eNETHYLCHOLESTA=S,22-D1LEN=3BETA=OL 4693 {8803 384 MAT*CH4 C27H440 (20 (22) E)sCHOLESTA=5,20(22) =DIEN=3BETA= OL &o98 $8723. 384 VW Ce7H440 CHOLESTA#S,20(24)"*DIEN=3BETA#OL 3299 99812 366 U C27H4b0 CHOLEST=8(14) =EN=3BETA=OL 234 06032 398 cEc=103 C28K460 2UeMETHYLCHOLESTA#5, 24025) =DIEN@SBETAWOL 234 09180 400 MAT*CHU C28H480 24~eMETHYLCHOLEST@B(14)=EN@=3BETA#OL 3518 {19479 410 U C29H460 22,23"™METHYLENE@2U™METHYLCHOLESTA=5,24(28)=DIEN@38-o 4785 19336 -dle MATCH C29H480 (22E) #24=DIMETHYLCHOLESTA#5,22=DIEN@3BETA*OL SR# s SAMPLE BOX NUMBER CATH » TABLET CATALOG NUMBER won COOK = CARL DJERASSI MASS SPECTRUM NUMBER » indicates that spectrum has C MW = MOLECULAR WEIGHT subsequently been moved to the ee MS 3 MASS SPECTROMETER Marine file. R CALL SPECTRA RECORDED AT 7O0EV) we we ee eee OOM TUMOUR DoOrnyouUeWVn-oO hr rhe tm Tm cwn- °° ~m wn UeDEMETHYL MARINE STEROL MASS SPECTRA CARL DJERASS!I FROM THE FILES OF JAN, 7, 1976 CALL SPECTRA RECORDED AT TOEYV) CATH co # MW MS FORMULA STEROL 5666 20660 370 U C26H420 2UmNOR=CHOLESTA#5S,227DIENwSBRETASOL 5339 18380 372 AET@MS9 C2bH4do 2yaNOR@CHOLEST*S™EN=3BETAROL 4739 99754 372 U C26Hu40 + (22E) = 9=NOR@SALPHA, 1 OBETASCHOLEST#22eEN=SBETA@OL 100 {6746 384 AEI=MS9 C27H4AD CHOLESTA=5, 7#0IEN@3BETA*OL es7 05570 364 MATCHA C27HUdo CHOLESTA@S, 2UDTEN@3BETA=O0L $03 $6793 384 AET=MS9 C27Ha4a PSALPHA~CHOLESTA=7,9C1 1) “DIEN*3SBETA*OL 473e 17657 486 UO, C27H460 CHOLES T=S"EN@SRETAOL 104 16778 386 AEY*MS9 C27HU60 SALPMApCHOLEST=7=EN=3BETA*OL 2509 18633 388 U C27H480 SALPHA=CHOLESTAN@3BETA“OL 406 05557 386 CECH#103 C27HUAO0 SALPHA*CHOLESTAN=3BETA=OL 4748 20063 398 AET=MS9 C28H460 (22£) ~24eMETHYLCHOLESTA=5, 22¥OTEN@3BETAROL e455 {Seid 398 U C28H460 (22£) w2UeMETHYLCHOLESTA@S, 22-DIEN@3BETA@OL 232 06060 398 MAT*CH4 C2aHdb0 24mHE THLYCHOLESTA*S, 24(28) sOLEN@3BETAWOL 233 09125 398 MAT*CHY C28HN60 (22E) n2UeMETHYL = SALPHASCHOLESTA=7,22"DIEN@3BETA=OL 3503 15281 uj2 AET*M39 C29HUB0 (22E) = 2URETHYLCHOLESTA=S, 22eD0IEN@SBETA*OL 2454 14916 “ie Vy) C29H480 (22E) «24HETHYLCHOLESTAW5S, 22-DIEN@3BETA*OL 236 06052 u{2 MATCH4 C29Hu80 (DOE) e2UeETHYL*SALPHAWCHOLESTAN7, 22-DIEN@SBETAMOL 2438 12489 a\2 U C29H480 C2UE) @STIGMASTA@S, 24 (28) *DIENWSBETA=OL -3U06 $1257 a{2 AEI=4S9 C29HUA0 (2UE)@STIGMASTA=5, 24 (28) =OLEN=3BETAWOL a7ue 99752 4ie2 U C29H4aod C2UE)@STIGMASTAWS, 24 (2B) =DIEN@SBETAWOL 238 06237 ie AETHHS9 C29HURO (2UE)“STIGHASTA#=5, 24 (28) -DIEN=3f-ol 4738 14100 Yi16 U C29HS20 2 UmETHYL@SALPHA=CHOLES TAN~3BE TA*OL 2450 13915 Y26 AET#HS9 C30HK500 GORGOSTEROL 4733 17659. 426 U- C30HS00 GORGOSTEROL , u7ug 19975 426 U C30HSO00 (247) ©24*PROPYL I DENECHOLEST#S~EN=3BETA=OL Spa = SAMPLE BOX NUMBER » indipates spectrum has been moved » CATH = TABLET CATALOG NUMBER Oo e synthetic file Cox © CARL DJERASSI MASS SPECTRUM NUMBER «“_.” indicates spectrum has subsequently — MW = KOLECULAR WEIGHT been deleted because of poor quality. MS 2 ASO MASS SPECTROMETER | 1977-78 Annual Report RR-00612 Section 7.2 References Bruce G. Buchanan and Dennis H. Smith, “Computer Assisted Chemical Reasoning," in E.V. Ludena, N.H. Sabelli and A.C. Wahl (eds.), Computers in Chemical Education and Research, New York: Plenum Press, 1977. P. 401 Bruce G. Buchanan, "Issues of Representation in Conveying the Scope and Limitations of Intelligent Assistant Programs," in D. Michie (ed.), Machine Intelligence 9, forthcoming. Bruce G. Buchanan and Tom Mitchell. "Model-Directed Learning of Production Rules," in D.A. Waterman and F. Hayes-Roth (eds.), Pattern-Directed Inference Systems, New York: Academic Press, forthcoming. Bruce G. Buchanan and Edward A. Feigenbaum, "DENDRAL and Meta-DENDRAL: Their Applications Dimension," Artificial Intelligence, forthcoming. Raymond E. Carhart and Dennis H. Smith, "Applications of Artificial Intelligence for Chemical Inference XX. Intelligent Use of Constraints in Computer-Assisted Structure Elucidation", Computers and Chemistry, 1, 79 (1976). Raymond E. Carhart, "A Model-Based Approach to the Teletype Printing of Chemical Structures," Journal of Chemical Information and Computer Sciences, 16, 82, 1976. R.E. Carhart, T.H. Varkony, and D.H. Smith, “Computer Assistance for the Structural Chemist," in "Computer- Assisted Structure Elucidation," D.H. Smith, (ed.), American Chemical Society, Washington, D.C., 1977, p. 126. C.J. Cheer, D.H. Smith and C. Djerassi, and B. Tursch, J.c. Braekman and D. Daloze, "Applications of Artificial Intelligence for Chemical Inference XXI: The Computer-Assisted Identification of [+]Palustrol in the 104 1977-78 Annual Report RR-00612 Section 7.2 9. 10. ll. 12. 13. 14. 15. 16. 17. Marine Organism Cespitularia sp., aff. Subviridis", Tetrahedron, 32, 1807 (1976). C. Djerassi, R. M. K. Carlson, S. Popov and T. 4&4. Varkony. Sterols from Marine Sources. In press. R. G. Dromey, Mark J. Stefik, Thomas C. Rindfleisch, and Alan M. Duffield, "Extraction of Mass Spectra Free of Background and Neighboring Component Contributions from Gas Chromatography/Mass Spectrometry Data," Analytical Chemistry, 48, 1368, August 1976. T.M. Mitchell and G.M. Schwenzer, "Applications of Artificial Intelligence for Chemical Inference XXV. A Computer Program for Automated Empirical 13C NMR Rule Formation," Organic Magnetic Resonance, forthcoming. Tom M. Mitchell, “Version Spaces: A Candidate Elimination Approach To Rule Learning," Proceedings of the Fifth IJCAI, 1, 305, August 1977. James G. Nourse, “Generalized Stereoisomerization Modes," Journal of the American Chemical Society, 99, 2063, 1977. S. Popov, R. M. K. Carlson, A-M. Wegmann and C. Djerassi. Occurrence of 19-Nor Cholesterol and Homologs in Marine Animals. Tetrahedron Lett., 3491 (1976). S. Popov, R. M. K. Carlson, A-M. Wegmann and C. Djerassi. Minor and Trace Sterols in Marine Invertebrates. l. Gener al Methods of Analysis. Steroids, 28, 699 (1976). Gretchen M. Schwenzer, "Applications of Artificial Intelligence for Chemical Inference. XXVI Analysis of C- 13 NMR for Mono-Hydroxy Steroids Incorporating Geometric Distortions," Journal of Organic Chemistry, forthcoming. Gretchen M. Schwenzer and Tom M. Mitchell, "Computer Assisted Structure Elucidation Using Automatically Acquired 13C NMR Rules," in D. Smith, (ed.), Computer Assisted Structure Elucidation, ACS Symposium Series, Vol. 54:58, 1977. 105 1977-78 Annual Report RR-00612 Section 7.2 18. 19. 20. 21. 22. 23. 24. 25. 26. D.H. Smith, (ed.), American "Computer-Assisted Structure Elucidation," Chemical Society, Washington, D.C., 1977. D.H. Smith, M. Achenbach, W.J. Yeager, P.J. Anderson, W.L. Pitch, and T.C. Rindfleisch, "Quantitative Comparison of Combined Gas Chromatographic/Mass Spectrometric Profiles of Complex Mixtures," Anal. Chem., 49, 1623 (1977). D.H. Smith and P.c. Jurs, "Prediction of 13C NMR Chemical Shifts," J. Am. Chem. Soc., submitted for publication. Dennis H. Smith and Raymond £E. Carhart, "Structure Elucidation Based on Computer Analysis of High and Low Resolution Mass Spectral Data," in M.L. Gross (ed.), Proceedings of the Symposium on Chemical Applications of High Performance Spectrometry, Washington, D.C.: American Chemical Society, in press. T.H. Varkony, R.E. Carhart, and D.H. Smith, “Applications of Artificial Intelligence for Chemical Inference XXIII. Computer-Assisted Structure Elucidation. Modelling Chemical Reaction Sequences Used in Molecular Structure Problems," in W.T. Wipke, (ed.), Computer- Assisted Organic Synthesis, Washington, D.C.: American Chemical Society, 1977. Tomas H. Varkony, Raymond E. Carhart, and Dennis H. ’ Smith, "Computer Assisted Structure Elucidation, Ranking of Candidate Structures, Based on Comparison Between Predicted and Observed Mass Spectra," in Proceedings of the Twenty-Fifth Annual Conference on Mass Spectrometry and Allied Topics, Washington, D.C., 1977. Tomas Varkony, Dennis Smith, and Carl Djerassi, “Computer- Assisted Structure Manipulation: Studies in the Biosynthesis of Natural Products," Tetrahedron, forthcoming. T.H. Varkony, R.E. Carhart, D.H. Smith, and C. Djerassi, "Computer-Assisted Simulation of Chemical Reaction Sequences. Applications to Problems’ of Structure Elucidation,” J. Am. Chem. Soc., submitted for publication. Annemar ie Wegmann, "Variations in Mass Spectral 106 1977-78 Annual Report RR-00612 Section 7.2 Fragmentation Produced by Active Sites in a Mass Spectrometer Source," Analytical Chemistry, forthcoming. 107 The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the res¥lt of this application. i [| ze i (ie Date Princlpal Investigator or Program Director 4