Natural products from around the world*

The structures of a range of natural products from Africa, Nepal, and Chile will be discussed. In principle, computer-assisted structure elucidation should facilitate the task of natural product chemists and speed up the process of resolving the structures of the many, often known, compounds that they isolate from natural sources. We have used the Logic for Structure Determination (LSD) program, developed by Dr. Jean-Marc Nuzillard of the University of Reims, France, to solve the structures of some diterpenoids from Salvia henkei [1]. These compounds presented no particular difficulties and could have been readily resolved without recourse to the computer by normal spectral analysis. Recently, we were challenged by the structures of three alkaloids, from the seeds of Acosmium panamense (Fabaceae), which defied all our efforts to find solutions without using the LSD program [2]. Column chromatography of the crude alkaloid mixture obtained from the seed extract afforded six compounds, four of them new. The two known alkaloids were readily identified as lupanine and multiflorine while one of the new compounds was assigned the structure 4α-angeloyloxy-3β-hydroxy-13βmethoxylupanine 1. The remaining three new compounds are acosmine 2, acosmine acetate 3, and panacosmine 4. Acosmine 2 has the molecular formula C21H33N3O2 (m/z 359). It contains an unusual N-acetyl enamine in addition to a vinyl group, a primary hydroxyl group, and two tertiary amines. The large coupling between the NH and the vinyl proton of the trisubstituted double bond (J = 11 Hz) confirms the presence of the enamine moiety. From COSY, HSQC and HMBC spectra several part structures could be deduced but a definitive structure proved elusive. The remaining bonds were deduced using HSQC and HMBC correlations as input to the LSD program. A single solution 2 was found in 0.1 s. Structure 2 is closely related to the lupanine/angustifoline skeleton. C-20 bridges the two nitrogens of a diazabicyclo[3.3.1]nonane system to form a diaza-adamantane skeleton, novel in natural product chemistry. The relative configurations of 2 follow from the constraints of the skeleton (C-7 and C-9 drawn to agree with those of lupanine) and from correlations in the ROESY spectrum. Disconnection of C-20 from N-1 and N-12 affords a molecule whose absolute configurations are the same as those of the corresponding centers in lupanine and angustifoline. Further support for the structure of acosmine was obtained from correlations in the H–N HMBC spectrum of the second new alkaloid, the corresponding primary acetate, acosmine acetate 3. Inter alia, correlations were observed from H-20 to both N-1 and N-12 and from H-21 to N-22. The final compound, panacosmine 4, has the molecular formula C21H31N3O [m/z 342, (M+1) ]. It exists as a mixture of amide rotamers (4:1) and this complicates spectral analysis because of superposition of signals. The resonances of the major component were used for the analysis with the LSD program. This provided 32 solution structures. In order to reduce this number a requirement that the solutions should contain the B,C ring system of angustifoline was introduced. Only two structures remained, of which 4 was preferred since it has the A,B,C ring system of angustifoline. Structure 4 also represents *Lecture presented at the 22 IUPAC International Symposium on the Chemistry of Natural Products, São Carlos, Brazil, 3–8 September 2000. Other presentations are published in this issue, pp. 549–626. the major amide rotamer since the vinyl proton of the minor rotamer is deshielded (∆δ = 0.6 ppm) by the carbonyl group. Chromatography of the methanol extract of the thalloid liverwort Marchantia paleacea Betrol subsp. paleacea, collected in Nepal, afforded the bisbibenzyl derivatives marchantins A, C, and D, 2hydroxy-3,7-dimethoxyphenanthrene and the interesting new compound, 3,4-dihydro-8-hydroxy-4-(4'hydroxyphenyl)-isocoumarin 5 [3]. Compound 5 was obtained as a gum. Its 1H NMR spectrum revealed two aromatic rings, one para-disubstituted [δH 6.99 and 6.76 (AA'BB', J = 8.6 Hz, H-2',6' and H-3',5')] and the other with three contiguous protons [δH 7.33 (t, J = 7.9 Hz, H-6), 6.86 (d, J = 8.4 Hz, H-5) and 6.41 (d, J = 7.5 Hz, H-7)], a bonded hydroxyl proton [δH 11.04 (s, 8-OH)], and a three spin system CH–CH2 [ABX] with the methylene group attached to oxygen [δH 4.57(dd, J = 11.0, 5.0 Hz, H-3), 4.50 (dd, J = 11.0, 8.6 Hz, H-3), 4.21 (dd, J = 5.0, 8.6 Hz, H-4)]. The carbon spectrum confirmed the presence of the two aromatic rings and the CH–CH2–OR system and additionally revealed the presence of an ester/lactone carbonyl group at δC170.0. The spin systems were readily observed in the COSY spectrum and the assignment of the protonated carbons followed from the HMQC spectrum. The above data can be assembled to give the 3,4dihydroisocoumarin structure 5. Confirmation of the structure of 5 was obtained from correlations in the HMBC spectrum which also permitted the assignment of the non-protonated carbons. Despite its simple structure the 3,4-dihydroisocoumarin 5 is a new natural product and has not been reported previously. Isocoumarins are usually polyketide in origin and are normally substituted on position 3. The isocoumarin hydrangenol 6, clearly a derivative of lunularic acid, has been reported in a liverwort by Becker and his colleagues [4]. J. D. CONNOLLY © 2001 IUPAC, Pure and Applied Chemistry 73, 567–571 568