From the alkaloidal fractions of the West African plant Cryptolepis sanguinolenta (Asclepiadaceae), two alkaloids were purified: one was identified as the known indoloquinoline alkaloid cryptolepine [1], A second, novel alkaloid was shown to have an empirical formula of C34H24N4O based on exact mass measurement. Through the concerted application of a series of homonuclear and inverse-detected 2D nmr experiments, the structure of the second alkaloid was established as a spiro-nonacyclic alkaloid, cryptospirolepine. One portion of the structure of cryptospirolepine [2] may be biogenetically derived from cryptolepine [1],Cryptolepis sanguinolenta (Lindl.) Schlechter (Asclepiadaceae), a shrub indigenous to West Africa, has long been employed by Ghanaian traditional healers in the treatment of various fevers, including malaria (1). A root decoction has been used in the clinical therapy both of malaria and of urinary and upper respiratory tract infections by Oku Ampofo at the Centre for Scientific Research into Plant Medicine in Ghana since 1974 (1). The indoloquinoline alkaloid cryptolepine (5-methyl-5H-indolo-[3,2-¿}quinoline) [1] was first isolated from extracts of the roots of Cryptolepis triangularis N. E.Br., a species native to the Belgian Congo, by Clinquart in 1929 (2). Shortly thereafter, the alkaloid was again isolated from the same species by Delvaux (3). Quite paradoxically, cryptolepine had been synthesized some 20 years prior by Fichter and coworkers (4-6). Cryptolepine was isolated from a Nigerian sample of Cr. sanguinolenta in 1951 by Gellert et al. (7). Almost 30 years later, the alkaloid was isolated from a

These experiments show a much shorter neuromuscular blocking effect and much-reduced side effects in the case of GW280430A vis-à-vis mivacurium. These results, together with the novel chemical degradation of GW280430A, suggest further evaluation in human subjects.

A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms. For all these benefits, combined NMR verification was expected and found by all metrics to be superior to validation by 1D (1)H NMR alone. Using multiple real-life data sets of chemical structures and the corresponding 1D and 2D data, it was possible to unambiguously identify at least 90% of the correct structures. As part of this test, challenging incorrect structures, mostly regioisomers, were also matched with each spectrum set. For these incorrect structures, the false positive rate was observed as low as 6%.

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