Gedunin and its Derivatives. This group consists of compounds wherein the D-ring has
undergone oxidative expansion. Baeyer- Villiger type oxidation of nimbinin (60), nimbocinol (55)
and 17 β / α hydroxy azadiradiones (53 and 54), can be expected to give D-ring lactones 65-69
respectively (Table 5). Gedunin (65) and its deacetyl derivative (66) have been found in neem
bark also in addition to their co-occurrence in neem seed oil. Gedunin was shown to posses
both antifugal115 and ant malarial properties. Nimolicionol (68) and Mahmoodin (69) belong to
deoxygedimn group. The presence of the novel C-17 glycolyl side chain in 69 was established
by nmr. and high resolution mass spectral (hrms) data. In hrms of 69, fragment ion peaks at
m/z 370.2127 (C23H3004) arising from the retro-Diels-Alder cleavage around ring C, and the
base peak at m/z 328.2029 (C21H2803) resulting from the subsequent loss of a ketene
molecule were quite significant. Its absolute stereochemistry was established through NOESY
spectral analysis and CD spectral data 147. It is postulated that biogenetically, its formation
may be considered from isonimolicinolide (41) through oxidation of ring D to δ -lactone, and
transformation of the acetoxy group to –OCH2CH2OH. Mahmoodin (69) was found moderately
antibacterial to several strains of human pathogenic bacteria.
undergone oxidative expansion. Baeyer- Villiger type oxidation of nimbinin (60), nimbocinol (55)
and 17 β / α hydroxy azadiradiones (53 and 54), can be expected to give D-ring lactones 65-69
respectively (Table 5). Gedunin (65) and its deacetyl derivative (66) have been found in neem
bark also in addition to their co-occurrence in neem seed oil. Gedunin was shown to posses
both antifugal115 and ant malarial properties. Nimolicionol (68) and Mahmoodin (69) belong to
deoxygedimn group. The presence of the novel C-17 glycolyl side chain in 69 was established
by nmr. and high resolution mass spectral (hrms) data. In hrms of 69, fragment ion peaks at
m/z 370.2127 (C23H3004) arising from the retro-Diels-Alder cleavage around ring C, and the
base peak at m/z 328.2029 (C21H2803) resulting from the subsequent loss of a ketene
molecule were quite significant. Its absolute stereochemistry was established through NOESY
spectral analysis and CD spectral data 147. It is postulated that biogenetically, its formation
may be considered from isonimolicinolide (41) through oxidation of ring D to δ -lactone, and
transformation of the acetoxy group to –OCH2CH2OH. Mahmoodin (69) was found moderately
antibacterial to several strains of human pathogenic bacteria.
Pro-C-seco-meliacins: Vilasinin and its Derivatives
Table 6 lists eleven neem constituents which when viewed from the biogenetic scheme represent as intermediates for the speciaIised
secondary metabolites of neem, the C-seco meliacins. In vepininlO6(70), the C-7 oxygen is bridged with C-15 giving rise to B-D ring fusion,
a characteristic feature of nimbin, salannin etc. Vepinin (70) could easily arise from any of the constituents belonging to azadirone group,
for instance, nimocinol (45). Instead of B-D ring fusion, oxidation of C-28 followed by C28-C6 linkage through Ether Bridge might account
for the formation of vilasinin108 (71) and its natural derivatives (73-76). Nimbolin-A (76) isolated from trunk bark contains a cinnamoyloxy
moiety at C-7 instead of acetoxy group as encountered in other cases. Kraus et al.,77 have recently added more natural derivatives of
Vilasinin from neem: 3-acetyl-7-tigloylvilasinin, 1-tigloyl-3 -acetylvilasinin. 12- α -acetoxy-7-tigloylvilasinin. l-acetyl-7¬tigloyl-12-oxo-vilasinin.
1-cinnamoyl-20,21,22,23-tetrahydro-23-hydroxyvilasinin and a position isomer (tigloyl attached to C-I instead of C-7 oxygen) of 77. They all
showed good insect antifeedant action against epilachna verivestis and .in. this respect were intermediate between azadirone derivatives
which were moderately active and the more active salannin derivatives. Functionalisation at C-12 was found to decrease the above activity.
It appears that saturated ring A with 1,3-dioxygen functions further linked by ether bridges between C-28 and C-6 on one end, C-7 and C-15
on another, as in salannin 85 and jts derivative is responsible. for the insect antifeedant action. The absence of second ether linkage in
Vilasinin probably explains their order of activity lower to salannins. Nimbidinin99 (72) and other Vilasinin derivatives containing C-12-
oxygen function can be considered as pro-C-secomeliacins. Limbocinin (78) and limbocidin (79) are highly oxygenated constituentsl44 of
this group, in which all the rings are intact but have been modified/linked with Oxygen Bridge. Azadirachtanin-A(80) is the unique case of the
meliacins, which contains a C19-C29 ether linkage but is devoid of an epoxide between C-14 and C-15112. Further, this is the only
constituent of neem, having the above referred ether bridge. For this unique reason, one must confirm its occurrence in a taxonomically
authenticated pure neem oil sample.
Table 6 lists eleven neem constituents which when viewed from the biogenetic scheme represent as intermediates for the speciaIised
secondary metabolites of neem, the C-seco meliacins. In vepininlO6(70), the C-7 oxygen is bridged with C-15 giving rise to B-D ring fusion,
a characteristic feature of nimbin, salannin etc. Vepinin (70) could easily arise from any of the constituents belonging to azadirone group,
for instance, nimocinol (45). Instead of B-D ring fusion, oxidation of C-28 followed by C28-C6 linkage through Ether Bridge might account
for the formation of vilasinin108 (71) and its natural derivatives (73-76). Nimbolin-A (76) isolated from trunk bark contains a cinnamoyloxy
moiety at C-7 instead of acetoxy group as encountered in other cases. Kraus et al.,77 have recently added more natural derivatives of
Vilasinin from neem: 3-acetyl-7-tigloylvilasinin, 1-tigloyl-3 -acetylvilasinin. 12- α -acetoxy-7-tigloylvilasinin. l-acetyl-7¬tigloyl-12-oxo-vilasinin.
1-cinnamoyl-20,21,22,23-tetrahydro-23-hydroxyvilasinin and a position isomer (tigloyl attached to C-I instead of C-7 oxygen) of 77. They all
showed good insect antifeedant action against epilachna verivestis and .in. this respect were intermediate between azadirone derivatives
which were moderately active and the more active salannin derivatives. Functionalisation at C-12 was found to decrease the above activity.
It appears that saturated ring A with 1,3-dioxygen functions further linked by ether bridges between C-28 and C-6 on one end, C-7 and C-15
on another, as in salannin 85 and jts derivative is responsible. for the insect antifeedant action. The absence of second ether linkage in
Vilasinin probably explains their order of activity lower to salannins. Nimbidinin99 (72) and other Vilasinin derivatives containing C-12-
oxygen function can be considered as pro-C-secomeliacins. Limbocinin (78) and limbocidin (79) are highly oxygenated constituentsl44 of
this group, in which all the rings are intact but have been modified/linked with Oxygen Bridge. Azadirachtanin-A(80) is the unique case of the
meliacins, which contains a C19-C29 ether linkage but is devoid of an epoxide between C-14 and C-15112. Further, this is the only
constituent of neem, having the above referred ether bridge. For this unique reason, one must confirm its occurrence in a taxonomically
authenticated pure neem oil sample.
Table 6. Limonoids with all carbocyclic rings intact and A ring carrying 1,3-dioxygen functions-Vilasinin (Vn.) group
Stru- Name Substituents Molecular m.p. Isolated Ref.
ture R1 R2 R3 Formula Weight (*C) from No.
No.
70. Vepinin - - - C28H36O5 452 Amorph. Seed oil 106
71. Vn. H H H C26H36O5 428 255 Green leaves 108
72. Nimbodinin H H H C26H34O6 442 282-4 Seed oil 99
(12-oxo- Vn.)
73. 1,3-Diascety Vilasinin Ac Ac H C30H40O7 512 157-8 Seed oil 70
74. Vilasinin triacetate Ac Ac Ac C32H42O8 554 228 Seed oil 108
75. I-Tigloyl-3-acetyl Vn. Tg Ac H C33H46O8 570 - Seed 74
76. Nimbolin A Ac Ac Cin C36H46O8 642 180-3 Heart wood 41
77. 3-Acetyl-7-tigloyl-Vn. La. - - - C33H46O8 570 242-3 Seed 22
78. Limbocinin - - - C35H42O11 638 - Seed
79. Limbocidin - - - C35H42O13 670 - Seed 144
80. Azadirachtanin-A - - - C10
32H40O11 600 225 Fresh leaves 112
ture R1 R2 R3 Formula Weight (*C) from No.
No.
70. Vepinin - - - C28H36O5 452 Amorph. Seed oil 106
71. Vn. H H H C26H36O5 428 255 Green leaves 108
72. Nimbodinin H H H C26H34O6 442 282-4 Seed oil 99
(12-oxo- Vn.)
73. 1,3-Diascety Vilasinin Ac Ac H C30H40O7 512 157-8 Seed oil 70
74. Vilasinin triacetate Ac Ac Ac C32H42O8 554 228 Seed oil 108
75. I-Tigloyl-3-acetyl Vn. Tg Ac H C33H46O8 570 - Seed 74
76. Nimbolin A Ac Ac Cin C36H46O8 642 180-3 Heart wood 41
77. 3-Acetyl-7-tigloyl-Vn. La. - - - C33H46O8 570 242-3 Seed 22
78. Limbocinin - - - C35H42O11 638 - Seed
79. Limbocidin - - - C35H42O13 670 - Seed 144
80. Azadirachtanin-A - - - C10
32H40O11 600 225 Fresh leaves 112
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