Adventures with Structure Elucidator.pdf

Adventures with Structure Elucidator G.E. Martin, D. Erdman, K.A. Blinov, A. Moser, A.J. Williams Pfizer Global RD, Kalamazoo Advanced Chemistry Development Moscow and Toronto Computer-Assisted Structure Elucidation ? Simple structure elucidation/characterization problems don’t warrant computer-assisted methods. Most can be solved by a competent spectroscopist in a minimal amount of time. ? When a competent spectroscopist spends any appreciable period of time working on the solution of a structure it becomes advisable to consider computer-assisted methods as a synergistic supplement to the human mind. Computer-Assisted Structure Elucidation ? CASE methods, to be viable, must have facile data entry protocols that allow quick entry of data that the program will consume. ? Ideally, CASE methods should be capable of advanced, logical assembly of candidate structures based on connectivity information (COSY, HSQC, HMBC, etc.). ? Chemical shift information available from both fragments and complete chemical structures should be used by the algorithms in conjunction with connectivity information. ? “Brute Force” calculation of all possible structures consistent with a given empirical formula is undesirable. Degradants of Cryptospirolepine N N CH3 O N NH CH3 ? 2.5 mg cryptospirolepine in d6-DMSO in a sealed NMR tube for 10 years. ? None of the starting alkaloid left but lots of degradation products. ? Degradation chemistry pathways don’t always obey the same “rules” that we use when we’re doing synthetic chemistry. ? Two major degradants were formed, DP-1 35% and DP-2 16% of the total. NN H (I) Quindoline N N CH3 (II) Cryptolepine (IX) Cryptospirolepine N H N H O (III) Quindolinone N N H O CH3 (VI) Homocryptolepinone NN CH3 (V) Cryptotackieine N N H N N HO (VIII) Cryptomisrine N N H O CH3 (IV) Cryptolepinone N N CH3 (VII) Cryptosanguinolentine N N CH3 O N NH CH3 Degradants of Cryptospirolepine When the characterization of the degradants of cryptos