Crystal and molecular structure of parthenolide [4,5-epoxygermacra-1(10),11(13)-dien-12,6-olactone]

Abstract

Crystal and MolecularStructure of Parthenolide [4,5-€poxygermacra-I (1 0),11(13)-dien-12,6-olactone] By Andrew Quick and Donald Rogers," Chemical Crystallography Laboratory, Imperial College, London SW7 2AYThe crystal structure of the title compound has been determined from single-crystal X-ray data by direct methods.Crystals are orthorhombic, a = 7 1.929(1), b = 12.267(2), c = 18.761 (2) 8, space group P212121, Z = 8, i.e. two independent niolecules per asymmetric unit. Full-matrix least-squares refinement based on 2 330 independent reflections has reached R 0.047. Thedouble bond C(l)-C(lO) and the equivalent double bond C(4)-C(5) are both rrans, both methyl groups are @, and the ten-membered ring has a conformation typical of several germacranolides.THE sesquiterpenic lactone, parthenolide, isolated from Chrysanthemum 9arthenizm (L) , was originally assigned the structure (I).l The same compound was isolated from the trunk bark of Michelia chaqbaca and its structure revised to (11) 2 from a study of its n.m.r. spectrum and chemical reactions. The absolute configuration of the molecule has been determined and it was shown that parthenolide can be represented by the stereoformula (111) .3The present crystal structure, part of a series of studies of ten-membered ring compounds, was undertaken to show the conformation of the epoxide ring and also the orientation of the methyls at C(4) and C(10). E SPERIMENTAL The crystals were colourless plates. Crystal Data.-C,,H,,O,, n/I = 248.3, Orthorhombic. a = 11.929(1), b = 12.267(2), c = 18.761(2) A, U = 2 745.4 A3, t Reprints are not available.

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones

“…Soon afterwards, the structure of PTL was revised through several degradation experiments and interpretation of NMR data, with the C-2/C-3 double bond assigned at the C-1 and C-10 positions, when it was isolated from the trunk bark of Michelia champaca L. (Magnoliaceae) [65]. The stereochemistry of the lactone ring of PTL was proposed by comparison of the analytical data of this epoxide with that of dihydrocostunolide [66], and supported later by analysis of its single-crystal X-ray diffraction data (Scheme 6) [67]. This was also confirmed by the total synthesis of PTL, which has been completed through a macrocyclic stereocontrolled Barbier reaction followed by a photoinduced Z/E isomerization (Scheme 6) [68].…”

Biogenetic Aspects of Sesquiterpene Lactone Chemistry

“…A possible difficulty with this biogenetic scheme is that both protons at the ring junction are cis, Hence the envisioned series of migrations is not likely to be concerted or non-stop." Subsequent biological oxidation of the 5-membered ring can be envisioned as leading to modified ambrosanolides such as psilostachyin C(54) or psilostachyin (56) 65 would lead directly to a compound with the structure and stereochemistry of microcephalin (66), while anti-Markownikow-orientated cyclization would lead to a trans-fused guaiane 67 with a stereochemistry appropriate for concerted loss of HX to pseudoivalin (68). It must be admitted, however, that biological oxidation of a {3-ocientated C 1 hydroxyl group expected from Scheme VIII followed by enzymatic reduction might obviously also give rise to the observed stereochemistry of 66 and that pseudoivalin (68) might be formed by simple proton loss from ion B of Scheme IX.…”

“…A possible difficulty with this biogenetic scheme is that both protons at the ring junction are cis, Hence the envisioned series of migrations is not likely to be concerted or non-stop." Subsequent biological oxidation of the 5-membered ring can be envisioned as leading to modified ambrosanolides such as psilostachyin C (54) or psilostachyin (56) To rationalize this finding, Parker, Roberts and Ramage' suggested the intermediacy of a cis-I(1O)-trans-4,S-germacradiene 65. As shown in Scheme X Markownikow-type trans-antiparallel cyclization of a cis,trans-germacradiene 65 would lead directly to a compound with the structure and stereochemistry of microcephalin (66), while anti-Markownikow-orientated cyclization would lead to a trans-fused guaiane 67 with a stereochemistry appropriate for concerted loss of HX to pseudoivalin (68).…”

Tunable Alignment for All Polymer Gel/Solvent Combinations for the Measurement of Anisotropic NMR Parameters

“…[11] A set of 16 one-bond RDCs could be obtained for the compound in a PAN/DMSO gel [12] stretched within the stretching apparatus equipped with a Kalrez 8002UP tube. RDCs fitted with the program PALES [13] confirm the presence of a chair-like conformation of the compound, as previously measured by X-ray crystallography [14] and as proposed by MM-calculations, [15] also in DMSO solution (see Figure 4 and Supporting Information).…”