Isolation and structure of daphnetoxin, the poisonous principle of Daphne species

Abstract

The 31P resonance of the trans form of 2 appears to show line broadening effects even when the cis isomer is in the slow-exchange limit (Figure 2). It is probable that the energy minimum for the trans molecule corresponds to the distorted structure indicated in Figure 3a and that the inequivalent phosphorus ligands are undergoing rapid intramolecular exchange.The passage of the cis and trans resonances in 2 to a simple quintet with increasing temperature shows that cis-trans isomerization via a polytopal1-4 rearrangement is operative here. The analysis of the hydride spectrum for compound 1 is the same as for 2 except that only the cis isomer was detected.The distortions in the cis and trans isomers indicated in Figure 3 suggest a polytopal rearrangement alternative to the trigonal or "Bailar" twist.5 The distortion modes could, in highly excited vibrational states, approach a tetrahedral disposition of phosphorus nuclei about the iron nucleus; hydrogen traverse (tunneling or classical) of trigonal faces would then complete the nuclear permutation process. This alternative is more attractive on steric grounds because of the obvious steric relief in the transition state. We cannot now rigorously distinguish between these two possible rearrangements, but detailed analysis of nmr transitional line shapes using the density matrix approach and analogous studies of other L4MH2 complexes now in progress may provide a definitive answer.Full details of spectral assignments and mechanistic studies will be published shortly.

Chemical constituents investigation of Daphne tangutica

“…In the HMBC spectrum, key correlations of H 3 -19/ C-3, H-5/C-4, H-20/C-6, H 3 -18/C-11, H 3 -17/C-3, H-16/C-17 confirmed the presumed daphne diterpene skeleton of compound 1, and the cross peaks of oxymethine proton signal at δ H 5.96 (1H, br s, H-14) with C-13 and C-8, suggested the esterification of the benzoyl group on C-14. The stereochemistry of compound 1 was identical with those known daphne diterpene derivatives [10][11][12] based on the analysis of the NOESY spectrum. The β orientation of C-19 (the methyl group at C-2) was determined by the NOE correlations of H 3 -19/H-1β, and H-2/H-10, the α position of the benzoyl group was deduced from the key NOE correlations between H-14 and H-8 (Fig.…”

“…By thus far, the reports on the naturally occurring daphnane diterpenes without this unusual feature are very limited [8,9]. Another notable difference between compound 1 and those known analogs found in the ring A [10][11][12]. In the 1 H NMR spectrum, instead of the signals of an olefinic proton and a vinylic methyl belonging to the α, β unsaturated carboxy group, protons of a methene group (δ H 2.26, m, 2H) and a secondary methyl group (δ H 1.26, d, J =7.0, 3H) were observed.…”

“…In our present study, two new daphnane derivatives (1 and 2), together with 28 known compounds, including six daphnane diterpenes, vesiculosin (3) [9], isovesiculosin (4) [9], gniditrin (5) [10], gnidicin (6) [10], daphnetoxin (7) [11] and excoecariatoxin (8) [12], nine coumarines, umbelliferone [13] (9), daphnoretin (10) [14], daphneticin (11) [5b], isodaphneticin (12) [15], daphnetin (13) [5c], daphnorin (14) [5c], daphnin (15) [16], daphnetin 8-O-β-D-glucopyranoside (16) [16] and daphneside (17) [16], six lignans, (−)-piperitol (18) [17] [19], (−)-pinoresinol glucoside (22) [18] and syringaresinol 4′,4″-di-O-β-D-glucopyranoside (23) [19], five phenylpropanoid derivatives, caffeic acid octadecyl ester (24) [20], trans-ferulic acid (25) [21], isoferulic acid (26) [22], icariside H 1 (27) [23] and syringin (28) [24], a steroid, β-sitosterol (29) and a small molecular compound, methyl phydroxy benzonate (30) [20] were purified and structurally identified. This is the first time that 13 known compounds, including 3,4,6,12,14,17,22,[24]...…”

Radical-Mediated Three-Component Reaction: A Study toward the Total Synthesis of Resiniferatoxin

“…In this reaction, the pre-installed C9-stereocenter as O,Se-acetal was to be transferred onto the C9-tetrasubstituted carbon of 1 in a stereospecific manner, while the C10-configuration would be transferred from that of the TBS-oxy group in A-ring 6e. The C-ring 18, the precursor of the key α-alkoxy bridgehead radical species, possessed the complex cyclohexane structure decorated with the five contiguous stereocenters (C8, 9,11,13,14), along with the bridgehead O,Se-acetal and the caged orthoester structures. Toward the synthesis of C-ring 18, we selected lactol 19 72,73) as the starting material from which a series of stereoselective transformations and optimization of the order of functionalization would be implemented.…”

“…9,10) The strong analgesic property of 1 caused by desensitization of nociceptive neurons offers 1 as a potential therapeutic agent. Two other daphnanes, daphnetoxin 11,12) and trigohownin A, 13) have more highly oxidized carbon frameworks and a phenyl orthoester and display different bio-functions: daphnetoxin is a human immunodeficiency virus (HIV) inhibitor while trigohownin A exhibits cytotoxic activity. The broad spectrum of bioactivity exhibited by daphnanes is attributed to the diverse pattern of oxygen functional groups on the trans-fused 5/7/6-membered tricarbocycle (ABC-rings) and two types of orthoester (C9,13,14-or C9,12,14-orthoester) decorated with a variety of substituents.…”