Extractives from the Meliaceae and Simaroubaceae of Madagascar.

13C NMR assignments for compound SM 1,5a.-stigmastan-3-one lHand 13C NMR assignments for compound SM2,samaderinB lHand 13C NMR assignments for compound SM3, samaderinE lHand 13C NMR assignments for compound assignmentsSMD4 framing CdaHadhe bruce sinX lHand 13C NMR assignments for compound SM6 ,15-acetylbruceinD. 1Hand13CNMR assignments for compound QP 11, quivisianone 1Hand13CNMR for compound QP 12, melianone 1Hand13CNMR assignments for compound QP 13, melianol.

ABSTRACT

Introduction

Triterpenoids of plant origin

POPO~

POPO~~W

1 1-2 IPP

1 102 IPP

Limonoids

They have also been reported from the genus Harrisonia, from another family in the order Rutales, Simaroubaceae. Harrisonia is the only genus within the family Simaroubaceae to produce imonoids, and its position within that family, no doubt prompted in part by this finding, is currently a matter of debate.

The Biosynthesis and Classification of Limonoids

They supported this proposal with a laboratory conversion of the 7a,8a-epoxy methyl emullate ester 1-49 to the corresponding 7a-hydroxyapo-derivative 1-50 by treatment with boron trifluoride etherate [45] (Scheme 10). A comparison of the structures presented on page 12 shows that the same side chains occur in both pre-apo change compounds and those in which the change has taken place, and therefore there is no specific stage at which it takes place.

HOVO~

Members of the class have a skeleton in which the A rings, the C band are intact, and the 0 ring is a six-membered lactone. The simplest class IV imonoid, cleavage of the C-7,C-8 bond in this group results in the formation of an exocyclic Ll8(30l-double bond and a carbomethoxy group at C-7.

P"TSOH

He then weakens his own counterargument on the grounds that the missing C-1 ketone resonance on which the structure of tabularine rests may be due to the weakness of the sample and not to the proposed structure. Members of the class have so far been isolated from only one species, Entandrophragma utile (Dawe et Sprague), and currently there are only four examples based on two structural templates, of which entilin A 1-33 and entilin D 1-89 are examples . 80.81].

Q Hof"jAt.~

Class XI

Oxidation of ring 0 apparently occurs independently of modifications of rings A and B; thus carapa spirolactone 1-118, in which ring 0 is intact, is separated from other class XI compounds, which possess a ring lactone [23] (Scheme 32a). As mentioned above, along with intact C-band rings, carapace spirolactone 1-118 has an intact 0-ring, while the 7-membered A-ring has shrunk to a 1,5-spirolactonevia cleavage of the C-1 bond, C-10 [ 23] (scheme 32b).

The Biological Activity of Limonoids

Quassinoids and the Simaroubaceae Family

The Simaroubaceae Family
A Brief Historical Review of the Biosynthesis, Structural Elucidation, and Biological Activity of Quassinoids

The triterpenoid precursor C-4 methyl groups in the latter publication are unfortunately mislabeled, which threatens to derail the entire thrust of the argument. The structure of the second C25quassinoid to be characterized was reported independently in 1970 as picrasin A 1-141 from the wood of Picrasma quassiodes Bennet [161] and nigakilactone G from Picrasma ailanthoides Planchon [162].

Figure 1: Subclassification of the the C2Q quassinoids by variations in the structure of the A ring {153].

HOC~~~

Sobel, A.E. de Candolle, C., in de Candolle, A Limonoids of the Meliaceae and Cneoraceae" i "Chemistry and Chemical Taxonomy of the Rutales", Annual Proceedings of the Phytochemical Society of Europe 22, Waterman, P.G. The Missouri Botanical Garden's VAST (VAScular Tropicos) nomenklaturdatabase på http://mobot.mobot.orgIW3T/Search/vast.html. Integreret system til klassificering af blomstrende planter·, Columbia University Press, New York. http://electrocomm.tripod.com/guassia .html. http://www.ocnsignal.com/yangtextg.shtml. http://www.tropilab.com/guassia-ama.htrnl 134. http://www.tinasherbs.com/hlistig.htm. http: //www.homestead.com/wirestumut/guassia.html og Lipshitz, Y., red., Interscience Publishers, London, s.385.

-Ngoc-Suong, Bhatnagar, S., Polonsky, J., Vuilhorgne, M., Prange, T. 1985) Progress in the Chemistry of Organic Natural Products,47, 221. and Moretti, C., unpublished results, cited in Polonsky, J.

Introduction

Turraea mombasana C.DC.: Examination of the root bark of a specimen of this East African shrub yielded the closely related prieurianin-c1ass limonoids mombasol 2-2 and mombasone 2-3 [12]. Turraea nilotica Kotschy et Peyr.: Iignan lariciresinol 4'·methyl ether 2-4, isolated from the cytotoxic extract of the leaves of a Sudanese sample [13], was found to be inactive [14]. In contrast, a previous study in this laboratory of stem bark and wood of a South African specimen found only the protolimonoid niloticin 2–6 and two related compounds, 2–7 and 2–8 [ 16 ].

A recent investigation [27] in this laboratory of the stem and root bark of this East African species yielded, together with the known havanensin-class vilasinin derivative 2-28, the new limonoid 12-D-methylnimbolinst2-29, havanensin -class cedrelone yielded 2·30 and neotrichilenone analogs, and the toonafolin-group compound 11-epi-toonacilin 2-35.

Extractives from Turraea sericea

34], sapelins A, C and D from Entandrophragma cylindricum Sprague [35,36], and chisocheton B 2-45 from Chisocheton paniculatus Hiern [37], by which time the 23R,24R stereochemistry was firmly established on a signature basis coupling constant of -9 Hz for J23,24' Despite these results and identical values for H-23 and H-24, the first fully assigned spectral data for bou~otinoloneA 2-40 from Trichilia hispida Pennington [38] appeared with the stereochemistry incorrectly represented . as 23R,24S. 42] do not specify the stereochemistry at C-1 in their compound 2-46, while Gunatilaka et al. specify their structure 2-48 as Sat C-1 without explanation. Assuming that the cleavage of the C-2,C-3 bond leaves the stereochemistry at C-1 unchanged, it is assigned as S in sericeanine A TS 1.

46] assign the stereochemistry at C-1 in their compound methyl argentinate 2·50 from Aglaia argentea Blume as S based on a NOESY correlation between H-1 and 3H-19, which is optimistic as rotation around C10,C- 1 bond would give rise to such a correlation regardless of the stereochemistry at C-1.

Table 2.1: 1H and 13C NMR assignments for compounds T5 1, sericeanin A, and T5 1a pH NMR 300MHz, 13C 75MHz, COCh, J in Hz]

Experimental

IR spectra were recorded on a Nicolet Impact 4000 Fourier-Transform Infrared (FT-IR) spectrometer using NaCl windows with CHCl:JCH3OH as solvents against an air background. GC/MS spectra were recorded on a Finnigan 1020 GC mass spectrometer and HRMS on a Kratos 9/50HRMS instrument at Cape Technikon.

34; Medicinal and poisonous plants of southern and eastern Africa", 2nd edition, E and S. Mulholland, DA and Taylor, DAH.

The effect of the structure of ring B on variations in the coupling constants J 9,11 and J 11 ,12

A literature survey and

A revision of the stereochemistry at C-11 in turraflorins A- C from Turraea floribunda

Introduction

This discrepancy led to a literature investigation into the effects of the structural features at C-8 and C-14, and especially the differences resulting from an open or intact ring B, on the coupling constants J9,11 andJ11 •12•.

Results and Discussion

Examination of molecular models reveals that while ring C can be chair-like in ring-B yellow compounds, giving rise to dihedral angles of -45° and -180° for H-9/H-11a and H-11a1H-12I3, respectively, it can only be boat-shaped if ring B is intact, with the corresponding angles both very close to 90°. Remarkably, within the broad open/closed ring B subdivision, the conformations adopted appear to be independent of the C-14,C-15 substitution pattern and/or the hybridization state of C-14 in particular. The compounds of the corresponding groups 0, E and F, which are all characterized by an open ring B, exhibit equally comparable J9,11 and J11 •12 values; cf.

The stereochemistry at C-11 in the turraflorines is therefore reassigned as~, giving revised structures 3·1a, 3.2a and 3·3a respectively for turraflorines A, Band C [12].

Extractives from Malleastrum antsingyense

Introduction

Formation of the 6u,28-ether bond does not appear to occur at a specific time in limonoid biosynthesis. 28] - and is virtually ubiquitous in the highly oxidized ringCopened nimbin group, suggesting that the ether formation definitely occurs after that of the furan ring and later rather than before. However, in limbocidin 4·7 and its 11,12-bis(deoxy) derivative 4-8[29], and more recently, azadirachtolide 4-9 and its 23-deoxy analog 4-10 [30], all from Azadirachta indica, ether formation is preceded the furan ring, although side chain cyclization and the associated loss of four carbons have occurred.

Comparison of the 1H and 13C NMR spectra of MA 2 with that of MA 1 showed that they were very similar, with MA 2 also having two acetate esters, a furan ring, and a C-14,C-15 double bond.

Table 4.2: lH and 13C NMR assignments for compound MA 2, 1,3-diacetyl-12a-hydroxy-7-tigloylvilasinin

Experimental

Introduction

Preface
Literature Survey

Typical of the confusion that often surrounds the classification of Simaroubaceous species is the observation that this species was originally described as Hyptandria bidwillii J.D.Hooker and ..subsequently. The biosynthetic and chemotaxonomic importance of the compounds isolated in this study from Samadera bidwillii lies in the fact that this is the first report to find a quassinoid, a limonoid, and bicyclooctane lignans co-occurring in a single species. Quassia amaraL.: or Surinamese quassia, is the source of the bitter crystalline principle quassin, which was first reported in 1835 [22].

Further investigation by the same researchers [34] resulted in the isolation of the new quassinoid derivatives and parain analogues 5-39,40.

Extractives from Samadera madagascariensis

However, a match of ~8~0.05 ppm for all signals in the 13C NMR spectrum was obtained in comparison with the unassigned values recorded from a total synthesis [60]. The additional carbon resonance, in conjunction with the absence of substituent esters in the 1H NMR spectrum, immediately suggested that 8M3 was a C20 quassinoid. In view of the similarities in the 13C NMR spectral data for this compound and for samaderin E 8M 3 and the acetyl ester 8M 6 for which HRMS values and molecular formulas were obtained, we consider the structure to be beyond doubt.

The rest of the 1H and 13C signals can be easily assigned compared to those of samaderine E 8M 3 and indaquassin X 8M 5, and are shown in Table 5.6.

Table 5.2: 1H and 13C NMR assignments for compound 8M 2, samaderine B pH NMR 400MHz, 13C 100MHz, CDCI3ICD30D, J in Hz]

Chemotaxonomic observations

Experimental

Extractives from Neobeguea leandreana

Introduction

This structure also gives the methyl groups at C-19 and C-28 as a and ~ respectively, and that of H-3 as a. However, the accompanying structure 6-43 is drawn with both the C-19 methyl group and the hydroxy group at C-2as~. The structure of xyloccensin E from Xylocarpus moluccansis (Lam.) M.Roem [9], identified as phragmalin 6-1 triacetate, was given as 6-4b (the comment that “2-H,3-H coupling requires that the oxygen at C -3 to be oriented." regardless), and that of the related ester from Chukrasia tabularis A.Juss [10] as 6-4c, while the configuration at C-2 in the 3-D perspective drawing and structure -4<1 is again inconsistent in a publication on busseins CoM from Entandrophragma busseiHarms.

Attempts to construct models with conformations not indicated in the perspective drawings confirm that this is the only possible conformation these molecules can assume.

Extractives from Neobeguea leandreana

Leandreanin A NL 1 therefore has structure 6-5. The fully assigned 1H and 13C NMR spectral data are given in Table 6.1 below. In this publication [15], the appearance of a peak at m/z 95 in the mass spectrum, corresponding to the fragment 6-9, is considered as •..convincing support. The quaternary methyl signals and corresponding ester carbonyl resonances in the 13C NMR spectrum are superimposed to the extent that they cannot be distinguished.

Despite the fact that the acetate ester methyl signals are well separated in the 1H NMR spectrum, they are also superimposed on underlying signals, making it very difficult to determine with certainty which signal is responsible for a given HMBC correlation, while it fact that three of these acetate esters occur at adjacent C-2, C-3, and C-30 make it virtually impossible to assign them based on NOESY correlations.

Table 6.1: 1H and 13C NMR assignments for compound NL 1, leandreanin A pH NMR 400MHz, 13C 100MHz, CDCb, J in Hz]

Experimental

Introduction

Extractives from Quivisia papinae

The fully assigned 1H and 13C NMR spectra, together with reference 13C NMR data for comparison, are given in Table 7.1 below. Although not mentioned in the publication, ring 0 in nimolicinol 7-15 is a hemiacetal and as such should show characteristic doubling of 13C NMR signals. Comparison of the 1H and 13C NMR spectra of QP2 with those of QP 1 showed that they are very similar, with the only difference being the appearance of a doublet at 84.41 (J Hz) in the 1H NMR spectrum, which in the HSaC spectrum is associated with the newly the oxymethine resonance at 068.15, while the C-6 methylene signal at 023.40 disappeared.

The fully assigned lHand 13C NMR spectral data, together with reference values for comparison, are given in Table 7.5 below.