A better understanding of the occurrence of various groups of neem meliacins can be made by
the knowledge of their probable biogenetic mechanism86.87.88 which is outlined in Scheme I.
According to the current view,38 the biogenesis is supposed to start from a tetracyclic
triterpenoid precursor of the tirucallol type. Limonoids belonging to this type (protolimonoids,
protomeliacins or melianes) constitute Group 1.
In neem, a few members (Meliantriol: nimolinone and nimbocinone) of this group have beep
found to occur, though the occurrence of tirucallol/euphol in neem is yet to be reported.
Epoxidation of 1:17 double bound followed by opening of the epoxide with a concurrent Wagner-
Meerwein shift of the C-14 methyl to C-8 leading to the formation of a double bond at C-14,15
and α hydroxyl group at C-7 can lead to the formation of compounds of Group 2. This type of
rearrangement is also well known as aporearrangement due to the formation of
apo¬tirucallane/apo-euphane derivatives84.85.86. In neem three such derivatives such as
azadirachtol have been so far reported and they also come under the group, protomeliacins.
Most of them and limonoids, have a C20 β:-H atom, though biosynthetic studies revealed that
euphol (with a C20 β-H) was incorporated much more efficiently in nimbolide of neem leaves
than tiirucallol42
found to occur, though the occurrence of tirucallol/euphol in neem is yet to be reported.
Epoxidation of 1:17 double bound followed by opening of the epoxide with a concurrent Wagner-
Meerwein shift of the C-14 methyl to C-8 leading to the formation of a double bond at C-14,15
and α hydroxyl group at C-7 can lead to the formation of compounds of Group 2. This type of
rearrangement is also well known as aporearrangement due to the formation of
apo¬tirucallane/apo-euphane derivatives84.85.86. In neem three such derivatives such as
azadirachtol have been so far reported and they also come under the group, protomeliacins.
Most of them and limonoids, have a C20 β:-H atom, though biosynthetic studies revealed that
euphol (with a C20 β-H) was incorporated much more efficiently in nimbolide of neem leaves
than tiirucallol42
There are two views on the formation of limonoids from Group 2. One view is that the side chain at C-21 loses four C-atoms and is further
modified to a y-hydroxy butenolide ring135 (Group 3), which is a precursor to C-17 furan ring (Group 4) while the other contrasting view38.
58 holds that side chain degradation directly leads to the formation of C-I7 furan ring which on further oxidative degradation furnishes the γ-
hydroxy butenolide system. Photo-oxidation58.163 of Group 4 to Group 3 lends credence to the latter view while the formation of cyclic
hemiaceta by the side chain of apo-skeleton prior to that of furan ring is cited as a supporting evidence for the first view.143 The isolation of
a few meliacins of Group 3 and a larger number azadirone derivatives (Group 4) from neem has been recorded. Further oxidative
degradation of Group 4 can lead to gedunin and its derivatives through ring D expansion88 (Group 5) as well as C-seco meliacins due to
ring C cleavage (Group-6). The formation of a few C.-seco hydroxybutenolides (Group 7) is expected either from Group 3 or Group 6,
analogous to earlier proposal. Further modifications lead to azadirachtins (Group 8). The biogenesis of gedunin type of limonoids is by
now well understood largely due to a great deal of investigations on the related compound limonin. The probable biogenetic pathways of
the C-seco meliacins38 seem to be formation of C-12 ketone which can then undergo oxidation to a lactone/lactol with a concurrent ring C
expansion and hydrolytic cleavage of ring C, concerted rotation of C8-C 14 axis and formation of ether bridge between C-7 (OH) and C-15.
The co-occurrence of nimbidinin (72), Nimbolin B (81), ohchinolide B (83) and meliacins containing C-12 aldehyde in neem and other
meliacean plants is in favour of such a hypothesis151. Recently, it has been shown that volkensin, a compound analogous to Nimbolin B
underwent an in vitro facile rearrangement to give nimbidic aldehydell3. Mechanistically, the alternate pathway involving the heterolytic
cleavage of C-12 carbonyl with an intermediate formation of C-12 acylium carbocation has been ruled out1oo. It may be mentioned here
that only plants belonging to the family Meliaceae specialise in the production of C-seco meliacins.
modified to a y-hydroxy butenolide ring135 (Group 3), which is a precursor to C-17 furan ring (Group 4) while the other contrasting view38.
58 holds that side chain degradation directly leads to the formation of C-I7 furan ring which on further oxidative degradation furnishes the γ-
hydroxy butenolide system. Photo-oxidation58.163 of Group 4 to Group 3 lends credence to the latter view while the formation of cyclic
hemiaceta by the side chain of apo-skeleton prior to that of furan ring is cited as a supporting evidence for the first view.143 The isolation of
a few meliacins of Group 3 and a larger number azadirone derivatives (Group 4) from neem has been recorded. Further oxidative
degradation of Group 4 can lead to gedunin and its derivatives through ring D expansion88 (Group 5) as well as C-seco meliacins due to
ring C cleavage (Group-6). The formation of a few C.-seco hydroxybutenolides (Group 7) is expected either from Group 3 or Group 6,
analogous to earlier proposal. Further modifications lead to azadirachtins (Group 8). The biogenesis of gedunin type of limonoids is by
now well understood largely due to a great deal of investigations on the related compound limonin. The probable biogenetic pathways of
the C-seco meliacins38 seem to be formation of C-12 ketone which can then undergo oxidation to a lactone/lactol with a concurrent ring C
expansion and hydrolytic cleavage of ring C, concerted rotation of C8-C 14 axis and formation of ether bridge between C-7 (OH) and C-15.
The co-occurrence of nimbidinin (72), Nimbolin B (81), ohchinolide B (83) and meliacins containing C-12 aldehyde in neem and other
meliacean plants is in favour of such a hypothesis151. Recently, it has been shown that volkensin, a compound analogous to Nimbolin B
underwent an in vitro facile rearrangement to give nimbidic aldehydell3. Mechanistically, the alternate pathway involving the heterolytic
cleavage of C-12 carbonyl with an intermediate formation of C-12 acylium carbocation has been ruled out1oo. It may be mentioned here
that only plants belonging to the family Meliaceae specialise in the production of C-seco meliacins.
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