20 Biogenesis of limonoids: The main features of triterpene biogenesis are now v;ell established and are summarised in scheme "1, The limonoids are def^raded triterpenes and constitute a group which derives its name from limonin, the bitter principle 3 9 present m most citrus species '•". Determination of the structure'of this principle was a magor problem in the mid fifties v/hich v;as solved through the efforts of several 10-12 internationally reno\^med chemists , Since NPIR spectroscopy had not yet arrived on the scene, the structure was deduced largely from chemical transformations of the molecule. X-ray analysis clarified such doubts as still existed and established besides the relative stereochemistry, The absolute configuration of limonin and other members of the group was assumed on the basis of biogenetic relationship to the tetracyclic triteri^ene tirucallol/euphol which had been previously related to compounds of known absolute configuration. Further confirmation v^as soon 1^ available through apolication of ORD -''. Evolution of the limonin carbcai skeleton from euDhol (3) involves elimin&tion of four carbon atoms of the
51
Embed
Biogenesis of limonoids - INFLIBNETshodhganga.inflibnet.ac.in/bitstream/10603/63676/6/06_discussion.pdf · Biogenesis of limonoids: The main features of triterpene biogenesis are
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
20
Biogenesis of limonoids:
The main features of triterpene biogenesis are
now v;ell established and are summarised in scheme "1, The
limonoids are def raded triterpenes and constitute a group
which derives its name from limonin, the bitter principle
3 9 present m most citrus species '•". Determination of the
structure'of this principle was a magor problem in the mid
fifties v/hich v;as solved through the efforts of several
10-12 internationally reno\ med chemists , Since NPIR
spectroscopy had not yet arrived on the scene, the structure
was deduced largely from chemical transformations of the
molecule. X-ray analysis clarified such doubts as still
existed and established besides the relative stereochemistry,
The absolute configuration of limonin and other members
of the group was assumed on the basis of biogenetic
relationship to the tetracyclic triteri ene tirucallol/euphol
which had been previously related to compounds of known
absolute configuration. Further confirmation v as soon
1^ available through apolication of ORD -''.
Evolution of the limonin carbcai skeleton from
euDhol (3) involves elimin&tion of four carbon atoms of the
21
side chain, cleavage of Gp-C., bond of ring A, migration of
C^^ methyl to G^ and modification of ring D. The limonin
nucleus emerges through oxidative cyclisation leading to
tv;o 5 membered and tv/o 5 membered heterocyclic rings. The
changes can be represented diagrammatically as shovm in
scheme - I.
[ SCHB\/!E I ]
Scission of r ing A as "oostulated in the 'blorcr.etlc
schene v/as o r i g i n a l l y observed in dammarenolic acid and
• 1 5 i s of v;ide occurrence among t r i t e r p e n e s e .g . shoreic acio - ,
22
. . 16 putranjivic acid and migration of the methyl group occurs
with introduction of double bond between C^^ and C. - during
oxidation of butyrospermyl acetate (5) to the 7-keto
compound (5) , Conversion of ring D to the 6 membered lactone
can occur through an in vivo enuivalent of the Baeyer -
Villiger oxidation. Many compounds have been isolated in the
intervening years which lie either on the pathv/ay to limonin
from euphol, or have resulted through scission and modifi
cation of other ring. '\
NZO'^'
H
ACO
(5) (6)
In the scheme that follows limonoids or their
immediate precursors have been so arranged as to place the
more primitive, and therefore siiapler ones, before the
23
structurally more complex. Protolimoaoids are compounds in
which structural changes of the precursor triterpene moiety
are confined to the side chain. Thus flindissol (7)
turraeanthin (8) aphanamixin (9) melianone (10) contain all
the carbon atoms of tirucallol/euphoi but cyclisation of
AcO
R = H r OH
(9)
do;
Lhe side chain to the Cdiurabcd furan has already occurred.
24
Cedrelone (11) and grandifolone (12) are representative of
compounds in v/hich methyl migration is accompanied by loss
of 4-carbon atoms from the side chain. Gedunine (13) type
t<=A
Kry o
(II)
ACO-
;i2)
R = H
of compounds are readily derivable from these through
Baeyer-Villiger rearrangement v/hile nomilin (I' O and
obacunone (15) are more obviously related to limonin (l&)
and ichangin (17) must be its immediate precursor.
25
(14) (15)
O^^'
;i6} (17
Also regarded as members of the limonoid group
arc andirobin (18) and methyl angolensate (19) in v/tiich
26
ring B undergoes scission and ring A remains intact, v/hereas
in nimbin (20) both rings A and B survi\-e and it is ring C
that is modified. Though more complex structurally
swietenolide (21) and mexicanolide (22) are readily accommo
dated in the scheme as products formed through cyclisation of
ring A with the methylene resulting fron scission of ring C,
^ COOCH
US) [19)
CH OC 2 II O
20) 21
COXI^
^
27
2 2 )
28
Structure elucidation of Limonoids;
NMR opectroscQ-py:
The structural problem of liraonin, as already
pointed out, v/as resolved largely through chemical trans
formations and PMR spectroscopy, applied at a later stage
of the work, served only to confirm the number of methyls.
The published data was meagre and only resonances of the
furanoid protons v;ere assigned. The first comprehensive
18 study of PI'IE spectra of limonoids was made by D,L.Dryer ,
vjho also employed it in confirming the structures assigned
to products resulting from deep-seated rearrangement of the
molecule.
In spite of the comparatively poor resolving
pov;er of the 60 KHz instruments, the spectra of limonin
and its derivatives reported by him are fa.irly clear, a
consequence of the wide difference in chemical shifts of
structurally significant protons and presence of but fev;
contiguous methylonos. It was thus possible to make
assignments with some certainty, the important ones being
of (a) methyl resonances (b) epoxidic protons (c) the C-1
and C-19 methine and methylene (d) furfuryl proton and (e)
90
the furanoid protons.
Methyl Resonance:
The C-8 methyl bei.ng farthest av;ay from deshielding
influences resonates at highest field followed by the
gem-dimethyls which are B to the ether ox;}'-gen and the / • — • ' '
18-methyl v/hich is in proximity to the luran ring. That the
resonance of the C-8 methyl is correctly identified follows
from the fact that it is the one most affected by reduction
01 carbonyl or its conversion to oxime. Similarly in obacunone
methyl assignments could be made on the basis of shifts
30
produced by opening of the 7-niembered lactone ring.
Protons under oxygen:
Of these there are five and of the five only the
one at C-1 is further coupled. The 0-19 methylene gives
rise to a singlet In some compounds and in others to AB
doublets. The singlet of the epoxide profcons v;as found to
overlap in some limonoids v/ith the mulfciplet of the C-1
proton but there is no ambig\,iity about the furfuryl proton
as, apart from its being on a carbon under oxygen, it is
further deshielded by the adjacent furan ring.
The epoxide proton appears at much lov;er field
than in similar compounds, because of uhe 0-7 carbonyl group.
The effect is similar to that observed, in case of 0-1
hydrogen in 11-ketosteroids ' nd 0-7 hydrogen in some
diterpenes e.g. fibleucin (23). Reduction of the 0-7 carbonyl
23)
31
gives two compounds, liraonol and epilimonol v/hich are
epimeric at C-7. The position of the epo;.dde proton
differs by about 40 Hz in the two compounds, Spilimonol,
the reduction product in which the epoxide hydrogen appears
at lower field, has been assigned equatorial [ OH as in
this case the hydroxy group ojid epoxide proton are in
proximity and the latter is thus exposed to the deshielding
influence of C-0 bond. An interesting fact that emerges
from a study of different limonoids is that the epoxidic
proton in compounds in which ring A is 7-Kiembored e.g.
obacunone (15) is at higher field than in limonin. Besides
serving to distinguish compounds of the two tj'~oes this
provides evidence of conformational changes in ring B on
expansion of ring A. Further the epoxidic ring also
influences the environment of the C-7 hydrogen in C-7
alcohol causing it to resonate at lovier field when it is
equatorial, as in limonolo Models shov/ that the epoxide
ring is also close tc the fu.riuryl proton and excercises
a deshielding influence on it too, for in dooxylimonin the
proton is shifted upfield hy about 20-30 Hz.
The stereochemistry at C-I7 was established
through recourse to Klyne's modification of Hudson's
32
19 lactone rule , The axial i.e. orientation of the
-fupfuryl proton is clearly discernible in columbin by the
larger coupling constant with the axial proton of the
adjacent methylene in columbin (24-) 20
24
33
Sfcructure of Janfpraolide:
The defatted bark of Jlacourtia cataphracta v;as
extracted v ich ethariol and acetone :..nd from the extract after
the usual purification a v.'hite cry£i:alline solid v/as
isolated. It had sharp melting poini; and initially appeared
pure on tic but the mass spectrum vras not very clear about
the position of M ' and the HMR too seemed to belong to a
mixture. The NHR spectrum shov/ed 8 t art-methyls atj high
field which suggested that the compound was a triterpene but
the mass spectrum had its most prominent ion at 5'J-8 with
peaks of very lov/ intensity only at higher mass values. It
was therefore presumed that the isolated solid was a mixture
of tv/o diterpenes. The IR spectrum (?ig-I) shov/ed a broad
-1 C^O band betv/een 17^0-. 1690 cm vi^n fine structure indicating
the presence of an ester or lactone grouping. Further
information about the structural features of vhc constituent
compounds was available from the ?'70 MHz HMR spectrum
(J ig-I- ). The presence of epoxide appeared likely but
integration over this region and the .uode of coupling v;as
not such as could be accorimodated within the fraraev/ork of
a di-or triterpene molecule and presence of other impurities
was susnccted„ The signals at lo'.'er field wore, ho\/ever,